High density lipoprotein complete list of trials: Difference between revisions

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(/* Phase Z of A-Z Trial{{cite journal |author=de Lemos JA, Blazing MA, Wiviott SD, et al. |title=Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial |journal=JAMA : ...)
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{{High density lipoprotein}}
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{{CMG}}; {{AE}} {{AN}}; {{RT}}
{{CMG}}; {{AE}} {{Hilda}}
==Reconstituted HDL Infusion==
{| class="wikitable sortable" style="font-size:90%"
! '''Name of the Trial'''
! '''Official Title'''
! '''Status'''
! '''ClinicalTrials.gov Identifier'''
! '''Drug name'''
! '''Trial phase'''
|-
|Effect of CER-001 on Atherosclerosis in Acute Coronary Syndrome (ACS) Patients - Efficacy and Safety: [[The CHI SQUARE Trial]] || CHI SQUARE: Can HDL Infusions Significantly Quicken Atherosclerosis Regression? A Phase II, Multi-Center, Double-Blind, Ascending Dose, Placebo-Controlled, Dose-Finding Trial of CER-001 or Placebo in Subjects With Acute Coronary Syndrome||Ongoing||NCT01201837 || CER-001 (an ApoA-I-based HDL mimetic)||2
|-
|Effect of CER-001 on Plaque Volume in Homozygous Familial Hypercholesterolemia (HoFH) Subjects (MODE)||Modifying Orphan Disease Evaluation (MODE) Study: A Multicenter, Open-label Study of the Effects of CER-001 on Plaque Volume in Subjects With Homozygous Familial Hypercholesterolemia (HoFH)||Ongoing||NCT01412034|| CER-001 (an ApoA-I-based HDL mimetic)||2
|-
|Exploratory Study of Plaque Regression (EXPRESS)||EXPLORATORY STUDY OF PLAQUE REGRESSION:A Phase II Single Center Open-Label Exploratory Trial of the Effect of CER 001 in Subjects With Familial Hypercholesterolemia||Completed|| NCT01515241|| CER-001 (an ApoA-I-based HDL mimetic)||2
|-
| [[A Multiple Ascending Dose Study of CSL112 in Healthy Volunteers]]||  An Adaptive, Phase I, Randomised, Placebo-controlled, Sponsor-unblinded, Multiple Ascending Dose Study to Investigate the Safety, Tolerability and Pharmacokinetics of Intravenous CSL112 in Healthy Volunteers|| Completed||NCT01281774 ||CSL112 (reconstituted HDL)||1
|-
| [[Safety, Tolerability and Pharmacokinetics of CSL112 in Healthy Volunteers]]||An Adaptive, Phase I, Single-Centre, Randomised, Double-blind, Placebo-controlled Single Ascending Dose Study to Investigate the Safety, Tolerability and Pharmacokinetics, of Intravenous CSL112 in Healthy Volunteers||Completed|| NCT01129661||CSL112 (reconstituted HDL)||1
|-
| [[A Single Ascending Dose Study Examining the Safety and Pharmacokinetic Profile of Reconstituted High Density Lipoprotein (CSL112) Administered to Patients]] || A Phase 2a, Multi-center, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study to Investigate the Safety, Tolerability and Pharmacokinetics of a Single Intravenous Infusion of CSL112in Patients With Stable Atherothrombotic Disease||Completed||NCT01499420 ||CSL112 (reconstituted HDL)||2
|-
|Effect of rHDL on Atherosclerosis - Safety and Efficacy:[[THE ERASE TRIAL]] ||Regression of Coronary Atherosclerotic Lesions After rHDL Infusions in Acute Coronary Syndrome Patients as Assessed by Intravascular Ultrasound||Completed||NCT00225719 ||rHDL||2
|-
|Improving Metabolism With HDL Cholesterol||A Novel Mechanism Mediating Anti-atherosclerotic and Metabolic Actions of HDL Cholesterol||Completed||NCT00395148||rHDL
|-
|[[Effect of Recombinant ApoA-I Milano on Coronary Atherosclerosis in Patients With Acute Coronary Syndromes]]|| || || ||Apo A-1 Milano, ETC 216, MDCO 216||3
|-
|}


==Overview==
==CETP Inhibitors==
Even though a causal relationship has not been established between low HDL-C levels in the serum and the incidence of coronary artery disease, low HDL-C is considered a significant risk factor for CAD.  Numerous clinical trials, like VA-HIT, AIM-HIGH, 4S etc., were conducted to study the effects of various novel lipid lowering agents on the levels of HDL-C and the corresponding changes in cardiovascular morbidity and mortality.  
{| class="wikitable sortable" style="font-size:90%"
! '''Name of the Trial'''
! '''Official Title'''
! '''Status'''
! '''ClinicalTrials.gov Identifier'''
! '''Drug name'''
! '''Trial phase'''
|-
| A Study of Evacetrapib in High-Risk Vascular Disease [[ACCELERATE Trial|(ACCELERATE)]] || Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibition With Evacetrapib in Patients at a High-Risk for Vascular Outcomes||Ongoing||NCT01687998||Evacetrapib||3
|-
| A Study of Evacetrapib (LY2484595) in Participants With Kidney Impairment and in Healthy Participants
  || Pharmacokinetics of Evacetrapib (LY2484595) Following Administration to Subjects With Impaired Renal Function


==Landmark Trials==
||Ongoing ||NCT01825889
===VA-HIT Trial<ref name="pmid18356553">{{cite journal |author=Robins SJ, Collins D, Nelson JJ, Bloomfield HE, Asztalos BF |title=Cardiovascular events with increased lipoprotein-associated phospholipase A(2) and low high-density lipoprotein-cholesterol: the Veterans Affairs HDL Intervention Trial |journal=Arterioscler. Thromb. Vasc. Biol. |volume=28 |issue=6 |pages=1172–8 |year=2008 |month=June |pmid=18356553 |doi=10.1161/ATVBAHA.107.160739 |url=}}</ref><ref name="pmid18078862">{{cite journal |author=Asztalos BF, Collins D, Horvath KV, Bloomfield HE, Robins SJ, Schaefer EJ |title=Relation of gemfibrozil treatment and high-density lipoprotein subpopulation profile with cardiovascular events in the Veterans Affairs High-Density Lipoprotein Intervention Trial |journal=Metab. Clin. Exp. |volume=57 |issue=1|pages=77–83 |year=2008 |month=January |pmid=18078862 |pmc=2194640 |doi=10.1016/j.metabol.2007.08.009 |url=}}</ref><ref name="pmid20855565">{{cite journal|author=Peloso GM, Demissie S, Collins D, ''et al.'' |title=Common genetic variation in multiple metabolic pathways influences susceptibility to low HDL-cholesterol and coronary heart disease |journal=J. Lipid Res. |volume=51 |issue=12 |pages=3524–32 |year=2010 |month=December |pmid=20855565 |pmc=2975725|doi=10.1194/jlr.P008268 |url=}}</ref><ref name="pmid17335828">{{cite journal |author=Robins SJ, Collins D, McNamara JR, Bloomfield HE |title=Body weight, plasma insulin, and coronary events with gemfibrozil in the Veterans Affairs High-Density Lipoprotein Intervention Trial (VA-HIT) |journal=Atherosclerosis |volume=196|issue=2 |pages=849–55 |year=2008 |month=February |pmid=17335828 |doi=10.1016/j.atherosclerosis.2007.01.029 |url=}}</ref>===
||Evacetrapib ||3
* OBJECTIVE: To conclude if changes in plasma lipid levels due to [[gemfibrozil]] is the cause for reduction in major cardiovascular events in VA-HIT trial.
|-
* METHOD: VA-HIT (Veterans Affairs HDL Intervention Trial) trial is a multicentered, randomized, double-blinded, placebo-controlled trial wherein 2531 patients with CAD along with LDL levels ≤140 mg/dL (mean 111 mg/dL) and HDL ≤40 mg/dL (mean 32 mg/dL) were randomly assigned to treatment with gemfibrozil or placebo.
| A Study of Evacetrapib in Healthy Participants
* RESULTS: At one year the following findings were noted in the group treated with gemfibrozil:
|| Effect of Gemfibrozil on the Pharmacokinetics of Evacetrapib (LY2484595) in Healthy Subjects || Completed|| NCT01736254
** Mean HDL-C level was higher by 6%
||Evacetrapib ||1
** 31% lower mean TG concentration
|-
** Mean total cholesterol was 4% lower
| A Study of Evacetrapib (LY2484595) in Participants With Hepatic (Liver) Impairment
||Pharmacokinetics of Evacetrapib (LY2484595) in Subjects With Hepatic Impairment  ||Ongoing ||NCT01836185
||Evacetrapib ||1
|-
|A Study of Evacetrapib (LY2484595) in Healthy Participants
  || A Bioequivalence Study in Healthy Subjects Administered Evacetrapib Tablets of Varying Tablet Solid Fractions || Ongoing||NCT01903434
||Evacetrapib ||1
|-
|  Study of Food on Evacetrapib (LY2484595) in Healthy Participants
|| Effect of Food on the Pharmacokinetics of Evacetrapib (LY2484595) in Healthy Subjects ||Completed ||NCT01810432
||Evacetrapib ||1
|-
| A Study of Evacetrapib and Rifampin in Healthy Participants
|| Effect of Rifampin on the Pharmacokinetics of Evacetrapib in Healthy Subjects ||Ongoing ||NCT01908582
||Evacetrapib ||1
|-
| A Study of LY2484595 on Pharmacokinetics in Healthy Subjects
|| A Phase 1 Study to Evaluate the Safety and Tolerability of LY2484595 SDSD-PG Tablets and the Effect of CYP3A Inhibition by Ketoconazole on the Pharmacokinetics of LY2484595 in Healthy Subjects || Completed|| NCT01448824
||Evacetrapib ||1
|-
| A Study of Evacetrapib (LY2484595) and Warfarin in Healthy Participants
|| Effect of Evacetrapib on the Pharmacokinetics and Pharmacodynamics of Warfarin in Healthy Subjects ||Completed ||NCT01825876
||Evacetrapib ||1
|-
| A Study of LY2484595 in Patients With High LDL-C or Low HDL-C
|| A Phase 2 Efficacy and Safety Study of LY2484595 Alone and in Combination With Atorvastatin, Simvastatin, and Rosuvastatin in Patients With Hypercholesterolemia or Low HDL-C ||Completed ||NCT01105975 ||Evacetrapib ||2
|-
| A Study of Evacetrapib in Healthy Female Participants
|| Effects of Evacetrapib (LY2484595) on the Pharmacokinetics of an Oral Contraceptive in Healthy Female Subjects ||Completed || NCT01746732
||Evacetrapib ||1
|-
| A Study of Evacetrapib and Digoxin in Healthy Participants
|| Effect of Evacetrapib on the Pharmacokinetics of Digoxin in Healthy Subjects ||Ongoing ||NCT01897493
||Evacetrapib ||1
|-
| A Study of LY2484595 in Healthy Subjects
||Single Dose LY2484595 Tablet Formulations to Determine the Impact of Dose Level, Food, and Ethnicity on the Pharmacokinetics in Healthy Subjects  || Completed||NCT01450098
||Evacetrapib ||1
|-
|A Study of LY2484595 in Japanese Subjects||A Phase 2 Dose Response Study of LY2484595 in Japanese Subjects||Completed||NCT01375075||Evacetrapib||2
|-
|A Study of LY2484595 on the Electrical Activity of the Heart||A Placebo- and Positive-Controlled Study of the Effect of LY2484595 on QT Interval in Healthy Subjects||Completed||NCT01537887
||Evacetrapib ||1
|-
|A Study of LY2484595 in Patients With High LDL-C or Low HDL-C||A Phase 2 Efficacy and Safety Study of LY2484595 Alone and in Combination With Atorvastatin, Simvastatin, and Rosuvastatin in Patients With Hypercholesterolemia or Low HDL-C||Completed||NCT01105975||Evacetrapib||2
|-
|A Study of LY2484595 on Pharmacokinetics in Healthy Subjects||A Phase 1 Study to Evaluate the Safety and Tolerability of LY2484595 SDSD-PG Tablets and the Effect of CYP3A Inhibition by Ketoconazole on the Pharmacokinetics of LY2484595 in Healthy Subjects||Completed||NCT01448824||Evacetrapib||1
|-
| A Study of RO4607381 in Stable Coronary Heart Disease Patients With Recent Acute Coronary Syndrome( [[dal-OUTCOMES Trial]])||A Randomized, Double-blind, Placebo-controlled Study Assessing the Effect of RO4607381 on Cardiovascular Mortality and Morbidity in Clinically Stable Patients With a Recent Acute Coronary Syndrome||Completed||NCT00658515||Dalcetrapib||3
|-
|A Formulation Screening Study of Dalcetrapib and Atorvastatin in Healthy Volunteers||A Single-center, Randomized, Open-label, Four Treatments, Four Periods, Four Sequence, Four-way Crossover Study to Explore the Pharmacokinetic Performance of Dalcetrapib and Atorvastatin Fixed Dose Combination Prototype Formulations in Healthy Volunteers||Completed||NCT01363999||Dalcetrapib|| 1
|-
|A Study of Dalcetrapib in Patients With Stable Coronary Heart Disease, With Coronary Heart Disease Risk Equivalents or at Elevated Risk for Cardiovascular Disease ||A Phase 3b, Multi-Center, Double-Blind, Placebo-Controlled, Parallel Group, Study to Evaluate the Effect of Dalcetrapib 600 mg on Cardiovascular (CV) Events in Adult Patients With Stable Coronary Heart Disease (CHD), CHD Risk Equivalents or at Elevated Risk for Cardiovascular Disease (CVD)||Completed||NCT01516541||Dalcetrapib||3
|-
|A Study of the Effect of Dalcetrapib on Artherosclerotic Disease in Patients With Coronary Artery Disease||A Multi-Center, Double-blind, Randomized, Placebo Controlled, Parallel Group Study of the Effect of Dalcetrapib on Atherosclerotic Disease Progression As Measured by Coronary Intravascular Ultrasound, Carotid B-Mode Ultrasound and Coronary Angiography||Completed||NCT01059682||Dalcetrapib
||3
|-
|A Study of Dalcetrapib in Patients Hospitalized For An Acute Coronary Syndrome (Dal-ACUTE) ||A Phase III, Double-blind, Randomized, Placebo-controlled, Multi-center Study Evaluating the Efficacy and Safety of Dalcetrapib on Lipids, Lipoproteins, Apolipoproteins and Markers of CV Risk in Patients Hospitalized for an Acute Coronary Syndrome (ACS) When Treatment is Initiated Within 1 Week After an ACS (Dal-ACUTE)||Completed||NCT01323153||Dalcetrapib||3
|-
|A Study of the Metabolic Profile of Dalcetrapib in Healthy Volunteers||An Open Label, Single Centre Study to Investigate the Metabolic Profile of Dalcetrapib After a Single Oral Dose in Healthy Male Subjects||Completed||NCT01476267||Dalcetrapib||1
|-
|A Study of RO4607381 in Stable Coronary Heart Disease Patients With Recent Acute Coronary Syndrome||A Phase II, Double-Blind, Randomized, Placebo-controlled, Parallel Group Study, Evaluating the Efficacy and Safety of RO4607381 Over a 24-week Period in Patients With CHD or a CHD Risk Equivalent||Completed||NCT00353522||Dalcetrapib||2
|-
|A Study Assessing the Effect of RO4607381 on Vascular Function in Patients With Coronary Heart Disease (CHD) or CHD-Risk Equivalent Patient [[Dal-VESSEL Trial]]||A Randomized, Placebo-controlled Study of the Safety, Tolerability and Effect on Endothelial Function, as Measured by Flow Mediated Dilatation, of RO4607381 in Patients With Coronary Heart Disease (CHD) or CHD Risk Equivalents||Completed||NCT00655538||Dalcetrapib||2
|-
|A Long Term Extension of Study NC19453 Evaluating Safety and Efficacy of RO4607381 ||A Phase II, Placebo-Controlled, Double-Blind Extension Study of Study NC19453 Assessing Long-term Safety and Efficacy of RO4607381||Completed||NCT00400439||Dalcetrapib||2
|-
|A Study of the Effect of RO4607381 on Atherosclerotic Plaque in Patients With Coronary Heart Disease ([[Dal-PLAQUE Trial]])||A Randomized, Placebo-controlled Study of the Effect of RO4607381 on Progression or Regression of Atherosclerotic Plaque in Patients With Coronary Heart Disease (CHD) Including Patients With Other CHD Risk Factors ||Completed||NCT00655473||Dalcetrapib||2


At five years, the combined primary end point of cardiac death and non-fatal [[myocardial infarction]] occurred in 17.3% versus 21.7% in the placebo group.  Acute coronary events reduced by 11% with gemfibrozil for every 5 mg/dL rise in HDL-C, but the reduction was independent of changes in [[LDL]]-C and [[triglyceride]] levels.
|-
* CONCLUSION: Low HDL-C levels strongly and independently predict the occurrence of coronary events which were reduced by treatment with gemfibrozil.
|Efficacy and Safety Study of JTT-705 in Combination With Pravastatin 40 mg in Patients With Type II Hyperlipidemia||A 4-Week, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study Evaluating the Efficacy and Safety of JTT-705 (300 mg or 600 mg) Versus Placebo in Combination With Pravastatin 40 mg in Patients With Type II Hyperlipidemia||completed||NCT00688896||Dalcetrapib||2
|-
|Efficacy and Safety of JTT-705 300, 600 And 900mg in Comparison With Placebo in Patients With Type II Hyperlipidaemia||A 4-Weeks Treatment, Randomised, Double-Blind, Parallel-Group Study Evaluating The Efficacy and Safety of JTT-705 300 to 900mg in Comparison With Placebo in Patients With Type II Hyperlipidaemia||Completed||NCT00686010||Dalcetrapib||2


===HATS Trial<ref name="pmid11757504">{{cite journal |author=Brown BG, Zhao XQ, Chait A, ''et al.'' |title=Simvastatin and niacin, antioxidant vitamins, or the combination for the prevention of coronary disease |journal=[[The New England Journal of Medicine]] |volume=345 |issue=22 |pages=1583–92 |year=2001 |month=November |pmid=11757504 |doi=10.1056/NEJMoa011090 |url=}}</ref>===
|-
* OBJECTIVE: To assess the effects of lipid-lowering drugs and/or antioxidant vitamins on progression or regression of coronary heart disease in patients with low HDL-C.
* METHODS: HDL-Atherosclerosis Treatment Study (HATS) was a randomized, 2 x 2 factorial study wherein 160 patients, both men and women with low HDL cholesterol, with at least one 50% stenotic coronary lesion or three 30% stenotic coronary lesions were enrolled. All the patients were randomized to four groups which were [[simvastatin]] plus [[niacin]], [[vitamin]]s, simvastatin-niacin plus [[antioxidant]]s; or placebos. The primary end points were arteriographic evidence of a change in coronary stenosis and the occurrence of a first cardiovascular event (death, myocardial infarction, stroke, or revascularization). Coronary angiograms were done at baseline and at three years to assess the change.
* RESULTS:
** In the simvastatin-niacin group mean LDL-C reduced by 42% and mean HDL-C increased by 26% while levels in the antioxidants and placebo groups remained unaltered.
** Rate of progression of coronary stenoses was low with simvastatin-niacin group compared to the other groups.
** Also, patients receiving simvastatin and niacin sustained lower cardiovascular events.
* CONCLUSION: Addition of a drug that increases HDL-C levels to a [[statin]] proves to have additional protection over just statin alone.


===AIM-HIGH Trial<ref name="pmid22085343">{{cite journal |author=Boden WE, Probstfield JL, Anderson T, ''et al.'' |title=Niacin in patients with low HDL cholesterol levels receiving intensive statin therapy |journal=N. Engl. J. Med. |volume=365 |issue=24 |pages=2255–67 |year=2011 |month=December |pmid=22085343|doi=10.1056/NEJMoa1107579 |url=}}</ref><ref name="pmid22520249">{{cite journal |author=Michos ED, Sibley CT, Baer JT, Blaha MJ, Blumenthal RS |title=Niacin and statin combination therapy for atherosclerosis regression and prevention of cardiovascular disease events: reconciling the AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health Outcomes) trial with previous surrogate endpoint trials |journal=J. Am. Coll. Cardiol. |volume=59 |issue=23|pages=2058–64 |year=2012 |month=June |pmid=22520249 |doi=10.1016/j.jacc.2012.01.045 |url=}}</ref><ref name="pmid22836067">{{cite journal |author=Brinton EA|title=Search and rescue for hypotheses surviving AIM-HIGH, the niacin therapy earthquake: still problematic after the primary publication |journal=J Clin Lipidol |volume=6 |issue=4 |pages=312–7 |year=2012 |pmid=22836067 |doi=10.1016/j.jacl.2012.03.005 |url=}}</ref><ref name="pmid22520248">{{cite journal|author=Nicholls SJ |title=The AIM-HIGH (Atherothrombosis Intervention in Metabolic Syndrome With Low HDL/High Triglycerides: Impact on Global Health Outcomes) trial: to believe or not to believe? |journal=J. Am. Coll. Cardiol. |volume=59 |issue=23 |pages=2065–7 |year=2012 |month=June|pmid=22520248|doi=10.1016/j.jacc.2012.02.021 |url=}}</ref><ref name="pmid22219232">{{cite journal |author=Nicholls SJ |title=Is niacin ineffective? Or did AIM-HIGH miss its target? |journal=Cleve Clin J Med |volume=79 |issue=1 |pages=38–43 |year=2012 |month=January |pmid=22219232 |doi=10.3949/ccjm.79a.11166|url=}}</ref><ref name="pmid21832894">{{cite journal |author=Sharma M |title=Combination therapy for dyslipidemia |journal=Curr. Opin. Cardiol. |volume=26|issue=5 |pages=420–3|year=2011 |month=September |pmid=21832894 |doi=10.1097/HCO.0b013e3283499ef1 |url=}}</ref>===
|Safety and Efficacy Study of JTT-705 in Combination With Atorvastatin 20 mg in Patients With Low High-Density Lipoprotein (HDL) Levels||A 4-Week, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study Evaluating the Safety and Efficacy of JTT-705 600 mg Versus Placebo Administered Once Daily in Combination With Atorvastatin 20 mg in Patients With Low HDL Levels||Completed||NCT00689442||Dalcetrapib||2
* OBJECTIVE: To assess if [[niacin]] + [[simvastatin]] combination is superior to simvastatin alone in raising low levels of [[high density lipoprotein]]([[HDL]]).
|-
* METHOD: AIM-HIGH is a randomized trial wherein 3414 patients randomly received either extended release niacin (1500 to 2000 md per day) or a matching [[placebo]]. All patients received simvastatin 40 to 80 mg daily to maintain an [[LDL]]-C level in the range of 40-80 mg/dL. [[Ezetimibe]] 10 mg daily was added, if needed, to achieve the LDL goal. The primary end point was the first event of the composite of death from [[coronary heart disease]], nonfatal [[myocardial infarction]], [[ischemic stroke]], hospitalization for an [[acute coronary syndrome]], or symptom-driven coronary or cerebral revascularization.
|Safety and Efficacy Study of JTT-705 in Combination With Simvastatin 40 mg in Patients With Low High-Density Lipoprotein (HDL) Levels||A 4-Week, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study Evaluating the Safety and Efficacy of JTT-705 600 mg Versus Placebo Administered Once Daily in Combination With Simvastatin 40 mg in Patients With Low HDL Levels||completed||NCT00688558||Dalcetrapib||2
* RESULTS: The trial was stopped prematurely for futility after a follow-up of 36 months.  At two years compared to placebo, niacin increased HDL-C levels and reduced [[triglyceride]] and LDL-C levels but there was no reduction in the rate of primary endpoint or all-cause mortality with niacin. Moreover, there was a trend towards more [[ischemic stroke]]s in the niacin group. This led to the decision to halt the trial prematurely.
* CONCLUSION: No incremental clinical benefit was observed from addition of niacin to simvastatin during a 36 month follow-up. Also, elevations in HDL-C levels in the placebo group were higher than expected which may have reduced the competency of the trial to detect a real benefit with niacin therapy.


===ARBITER 2 Trial<ref name="pmid15537681">{{cite journal |author=Taylor AJ, Sullenberger LE, Lee HJ, Lee JK, Grace KA |title=Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol (ARBITER) 2: a double-blind, placebo-controlled study of extended-release niacin on atherosclerosis progression in secondary prevention patients treated with statins |journal=Circulation |volume=110 |issue=23 |pages=3512–7 |year=2004 |month=December |pmid=15537681 |doi=10.1161/01.CIR.0000148955.19792.8D |url=}}</ref>===
|-
* OBJECTIVE: To assess if treatment with extended release [[niacin]] when added to [[statin]] monotherapy slows progression of [[atherosclerosis]] among individuals with known [[coronary artery disease]] ([[CAD]]) and moderately low HDL-C.
|Study to Assess the Tolerability and Efficacy of Anacetrapib in Patients With Coronary Heart Disease (CHD) or CHD Risk-Equivalent Disease (MK-0859-019 AM6; EXT1 [AM2]) ([[DEFINE Trial]])||A 76-Week, Worldwide, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study to Assess the Tolerability and Efficacy of Anacetrapib When Added to Ongoing Therapy With a Statin in Patients With Coronary Heart Disease (CHD) or CHD Risk-Equivalent Disease||Ongoing||NCT00685776||Anacetrapib||3
* METHOD: ARBITER (Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol) 2 was a double blinded randomized placebo controlled study of once daily extended release niacin (1000 mg). 167 patients with known CAD and moderately low HDL-C were enrolled in this study and were assessed for the primary end-point [[carotid intima-media thickness]] (CIMT) at the end of one year.
|-
* RESULTS: At the end of 12 months mean CIMT significantly increased in the placebo group but not in the niacin group. Niacin significantly reduced the rate of IMT progression in patients without [[insulin resistance]]. Patients treated with niacin had a significant increase in [[HDL]] levels from a mean of 39 mg/dL to 47 mg/dL.  
|A Study of the Safety and Efficacy of Anacetrapib (MK-0859) When Added to Ongoing Statin Therapy (MK-0859-021 AM1)||A 24-Week, Worldwide, Multicenter, Double-Blind, Randomized, Parallel, Placebo-Controlled Study to Assess the Efficacy and Tolerability of Anacetrapib When Added to Ongoing Statin Therapy With or Without Other Lipid Modifying Medication(s) in Patients With Hypercholesterolemia or Low HDL-C||Ongoing||NCT01717300||Anacetrapib||3
* CONCLUSION: The addition of extended-release niacin to statin therapy slowed the progression of atherosclerosis among individuals with known coronary heart disease and moderately low HDL-C.
|-
|A Study of the Safety and Efficacy of Anacetrapib (MK-0859) When Added to Ongoing Statin Therapy in Japanese Participants With Dyslipidemia (MK-0859-051 AM1)||A Multicenter, 24-Week, Double-Blind, Randomized, Placebo-Controlled, Phase III Study With 28-Week Open Labeled Extension Period to Assess the Efficacy and Safety of MK-0859 When Added to Ongoing Statin Therapy With or Without Other Lipid Modifying Medication(s) in Japanese Patients With Dyslipidemia||Ongoing||NCT01760460||Anacetrapib||3
|-
|Pharmacokinetics of Anacetrapib (MK0859) in Patients With Hepatic Insufficiency (MK-0859-039)||A Single Dose Study to Investigate the Pharmacokinetics of MK0859 in Patients With Hepatic Insufficiency||Completed||NCT01114490||Anacetrapib||1
|-
|A Study of the Safety and Efficacy of Anacetrapib (MK-0859) When Added to Ongoing Statin Therapy in Japanese Participants With Heterozygous Familial Hypercholesterolemia (MK-0859-050)||A 12-Week, Multicenter, Double-Blind, Randomized, Parallel, Placebo-Controlled Study to Assess the Efficacy and Safety of MK-0859 When Added to Ongoing Statin Therapy With or Without Other Lipid Modifying Therapies in Japanese Patients With Heterozygous Familial Hypercholesterolemia|| Ongoing||NCT01824238||Anacetrapib||3
|-
|Pharmacokinetics of Anacetrapib (MK0859) in Subjects With Impaired Renal Function (MK-0859-038)||A Single-Dose Study to Investigate the Pharmacokinetics of MK0859 in Subjects With Impaired Renal Function||Completed||NCT01122667||Anacetrapib||1
|-
|[[REVEAL Trial|REVEAL]]: Randomized EValuation of the Effects of Anacetrapib Through Lipid-modification||REVEAL: Randomized EValuation of the Effects of Anacetrapib Through Lipid-modification. A Large-scale, Randomized Placebo-controlled Trial of the Clinical Effects of Anacetrapib Among People With Established Vascular Disease||Ongoing||NCT01252953||Anacetrapib||3
|-
|Efficacy and Tolerability of Anacetrapib Added to Ongoing Lipid-Lowering Therapy in Adult Participants With Homozygous Familial Hypercholesterolemia (HoFH) (MK-0859-042 AM2)||A Worldwide, Multicenter, Double-Blind, Randomized, Placebo-Controlled, 12-Week Study to Assess the Efficacy and Tolerability of Anacetrapib When Added to Ongoing Lipid-Lowering Therapy in Adult Patients With Homozygous Familial Hypercholesterolemia (HoFH)||Ongoing||NCT01841684||Anacetrapib||3
|-
|A Study of the Safety and Efficacy of Anacetrapib (MK-0859) Among Participants With Hypercholesterolemia When Added to Ongoing Statin Therapy (MK-0859-022 AM4)||A 24-Week, Worldwide, Multicenter, Double-Blind, Randomized, Parallel, Placebo- Controlled Study to Assess the Efficacy and Tolerability of Anacetrapib When Added to Ongoing Statin Therapy With or Without Other Lipid Modifying Medication(s) in Patients With Hypercholesterolemia or Low HDL-C||Ongoing||NCT01860729||Anacetrapib||3
|-
|A Study of the Safety and Efficacy of Anacetrapib (MK-0859) Among Participants With Hypercholesterolemia When Added to Ongoing Statin Therapy (MK-0859-022 AM4)||A 24-Week, Worldwide, Multicenter, Double-Blind, Randomized, Parallel, Placebo- Controlled Study to Assess the Efficacy and Tolerability of Anacetrapib When Added to Ongoing Statin Therapy With or Without Other Lipid Modifying Medication(s) in Patients With Hypercholesterolemia or Low HDL-C||Ongoing||NCT01860729||Anacetrapib||3
|-
|Study to Assess the Tolerability and Efficacy of Anacetrapib Co-administered With Statin in Participants With Heterozygous Familial Hypercholesterolemia (MK-0859-020 AM1) (REALIZE)||A 1-Year, Worldwide, Multicenter, Double-Blind, Randomized, Parallel, Placebo- Controlled Study to Assess the Efficacy and Tolerability of Anacetrapib When Added to Ongoing Statin Therapy With or Without Other Lipid Modifying Medication(s) in Patients With Heterozygous Familial Hypercholesterolemia||Ongoing||NCT01524289||Anacetrapib||3
|-
|A Study of Safety and Efficacy of MK0859 (Anacetrapib) in Japanese Patients With Dyslipidemia (0859-029)(COMPLETED)||A Phase IIb, Multicenter, Randomized, Placebo-Controlled, Double-Blind, Dose-Ranging Study to Assess the Efficacy and Safety of MK0859 in Japanese Patients With Dyslipidemia||Completed||NCT00977288||Anacetrapib||2
|-
|The Effect of MK0859 on Lipoprotein Metabolism in Patients With Dyslipidemia (0859-026 AM3)||A Multiple Dose Study to Investigate the Effect of MK0859 on Lipoprotein Metabolism When Added to Ongoing Statin Therapy in Dyslipidemic Patients||Completed||NCT00990808||Anacetrapib||1
|-
|MK0859 Dose-Ranging Study (0859-003||MK0859 Dose-Ranging Study||Terminated||NCT00325455||Anacetrapib||2
|-
|A Study of MK0859 in Patients With Primary Hypercholesterolemia or Mixed Hyperlipidemia|| ||Completed||NCT00565292||Anacetrapib||1
|-
|A Study Examining Torcetrapib/Atorvastatin And Atorvastatin Effects On Clinical CV Events In Patients With Heart Disease [[ILLUMINATE Trial|(ILLUMINATE)]]||Phase 3 Multi Center, Double Blind, Randomized, Parallel Group Evaluation Of The Fixed Combination Torcetrapib/Atorvastatin, Administered Orally, Once Daily (Qd), Compared With Atorvastatin Alone, On The Occurrence Of Major Cardiovascular Events In Subjects With Coronary Heart Disease Or Risk Equivalents||Terminated||NCT00134264|| Torcetrapib||3
|-
| Assess HDL-C Increase And Non-HDL Lowering Effect Of Torcetrapib/Atorvastatin Vs. Fenofibrate|| Phase 3 Multi-Center, Double-Blind, Randomized, Parallel Group, Forced Titration Study Of The Efficacy, Safety, And Tolerability Of Torcetrapib/Atorvastatin Compared To Fenofibrate In Subjects With Fredrickson Type IIB Dyslipidemia (Mixed Hyperlipidemia || Completed ||NCT00139061
||  Torcetrapib ||3
|-
| Study To Evaluate The Effect Of Torcetrapib/Atorvastatin In Patients With Genetic High Cholesterol Disorder
|| Phase 3 Multi-Center, Open Label, Forced Titration Study To Evaluate The Efficacy, Safety, And Tolerability Of Torcetrapib/Atorvastatin Combination Administered Orally, Once Daily (Qd) In Patients With Homozygous Familial Hypercholesterolaemia ||  Completed  ||NCT00134511
||  Torcetrapib ||3
|-
|Study To Evaluate The Safety And Efficacy Of Torcetrapib/Atorvastatin In Subjects With Familial Hypercholerolemia || Phase 3, Multi-Center, Double-Blind, Randomized, Parallel Group, Study of the Efficacy, Safety, and Tolerability of Fixed Combination Torcetrapib (CP-529,414) / Atorvastatin Administered Orally, Once Daily (QD) for Six Months, Compared With Maximally Tolerated Atorvastatin Therapy Alone, in Subjects With Heterozygous Familial Hypercholesterolemia ||  Completed  ||NCT00134485 ||  Torcetrapib ||3
|-
|Study To Evaluate The Effect Of Torcetrapib/Atorvastatin In Subjects With A Genetic Cholesterol Disorder||Phase 3, Multi-Center, Double-Blind, Randomized, Crossover Study Of The Efficacy, Safety, And Tolerability Of Fixed Combination Torcetrapib (Cp-529,414)/Atorvastatin, Compared With Atorvastatin Therapy Alone, And Fenofibrate Alone, In Subjects With Fredrickson Type III Hyperlipoproteinemia (Familial Dysbetalipoproteinemia)  ||  Terminated  ||NCT00145431
||  Torcetrapib || 3
|-
| A Study Comparing The Efficacy & Safety Of Torcetrapib/Atorvastatin And Atorvastatin In Subjects With High Triglycerides || Phase 3, Multi-Site, Double-Blind, Randomized, Forced Titration, Parallel Group Evaluation Of The Efficacy, Safety, And Tolerability Of Fixed Combination Torcetrapib (CP 529,414)/Atorvastatin Administered Orally, Once Daily (Qd) For Eighteen Weeks, Compared With Atorvastatin Alone, In Subjects With Fredrickson Type IV Hypertriglyceridemia ||  Completed  || NCT00134498||  Torcetrapib||3
|-
| A Clinical Trial Comparing Torcetrapib/Atorvastatin To Simvastatin In Subjects With High Cholesterol || A Phase 3, Open-Label, Multisite, Randomized, Parallel Group Study of the Efficacy and Safety of Fixed Combination Torcetrapib/Atorvastatin Administered Once Daily (QD) Compared to Simvastatin for 6 Weeks in Subjects With Hypercholesterolemia (A5091030) ||  Completed  ||NCT00267254||  Torcetrapib ||3
|-
| A Study of Torcetrapib/Atorvastatin vs Atorvastatin Alone or Placebo in Patients With High Cholesterol||A Phase 3, Double Blind, Placebo-Controlled, Randomized, Parallel Group, Multicenter Study of the Efficacy, Safety and Tolerability of Fixed Combination Torcetrapib/Atorvastatin Administered Orally Once Daily for 6 Months, Compared to Atorvastatin Alone or Placebo in Subjects With Mixed Dyslipidemia (Fredrickson Types IIa and IIb).|| Completed  ||NCT00138762||  Torcetrapib ||3
|-
|A Clinical Trial Comparing Torcetrapib/Atorvastatin To Simvastatin In Subjects With High Cholesterol (A5091031). ||A Phase 3, Open-Label, Multisite, Randomized, Parallel Group Study of the Efficacy and Safety of Fixed Combination Torcetrapib/Atorvastatin Administered Once Daily (QD) Compared to Simvastatin for 6 Weeks in Subjects With Hypercholesterolemia (A5091031)  ||  Terminated||NCT00267280||  Torcetrapib || 3
|-
| A Clinical Trial Comparing Torcetrapib/Atorvastatin to Ezetimibe/Simvastatin In Subjects With A Cholesterol Disorder.
|| Phase 3, Open-Label, Multi-Center, Double-Blind, Randomized, Parallel Group Study Efficacy and Safety of Fixed Combination Torcetrapib/Atorvastatin, Administered Once Daily (QD) Compared to Fixed Combination Ezetimibe/Simvastatin for 6 Weeks in Subjects With Dyslipidemia ||Terminated  ||NCT00267267
||  Torcetrapib||3
|-
| Carotid B-mode Ultrasound Study to Compare Anti-Atherosclerotic Effect of Torcetrapib/Atorvastatin to Atorvastatin. (RADIANCE 2)
|| Phase 3 Multi-Center, Double-Blind, Randomized, Parallel Group, Carotid B-mode Ultrasound Evaluation of the Anti-Atherosclerotic Efficacy, Safety, and Tolerability of Fixed Combination CP-529,414/Atorvastatin, Administered Orally, Once Daily (QD) for 24 Months, Compared With Atorvastatin Alone, in Subjects With Mixed Hyperlipidemia || Terminated || NCT00134238
||  Torcetrapib||3
|-
| A Coronary IVUS Study to Compare Torcetrapib/Atorvastatin to Atorvastatin Alone in Subjects With Coronary Heart Disease [[ILLUSTRATE Trial|(ILLUSTRATE)]] ||  Phase 3, Multi-Center, Double-Blind, Randomized, Parallel Group, Coronary Artery Intravascular Ultrasound Evaluation of the Anti-Atherosclerotic Efficacy, Safety, and Tolerability of Fixed Combination CP-529,414/Atorvastatin, Administered Orally, Once Daily (QD) for 24 Months, Compared With Atorvastatin Alone, in Subjects With Angiographically Documented Coronary Heart Disease.  


===ARBITER 3 Trial<ref name="pmid17076985">{{cite journal |author=Taylor AJ, Lee HJ, Sullenberger LE |title=The effect of 24 months of combination statin and extended-release niacin on carotid intima-media thickness: ARBITER 3 |journal=[[Current Medical Research and Opinion]] |volume=22 |issue=11 |pages=2243–50 |year=2006 |month=November |pmid=17076985 |doi=10.1185/030079906X148508 |url=}}</ref>===
|| Completed ||NCT00134173 ||Torcetrapib|| 3
* OBJECTIVE: To study the effects of long term treatment with extended release niacin (ERN) on [[HDL]] levels and carotid intima- media thickness in patients who participated in ARBITER 2.
|-
* METHODS: 88% (149) of patients enrolled in the ARBITER trial participated in the ARBITER 3 trial, those who either were continued or crossed over to the placebo group. The long term effects of ERN on HDL cholesterol and carotid intima- media thickness were examined during 12- 24 months of treatment.
| Safety FollowUp Study Of Cardiovascular Events In Subjects Who Participated In Selected Torcetrapib/Atorvastatin Studies
* RESULTS:
|| An Observational Safety Follow Up Trial Of The Occurrence Of Major Cardiovascular Events And All Cause Mortality In Subjects Who Participated In Selected Torcetrapib/Atorvastatin Clinical Trials. || Terminated ||NCT00452842||   Torcetrapib|| Observational
** The ERN group showed an increase in [[HDL]]-C levels along with modest reductions in [[LDL]]-C and [[triglycerides]].
|-
** A net regression in CMIT was seen in patients treated with ENC for 12 months.
| Lipitor Trial To Study The Effect Of Torcetrpib/Atorvastatin To Atorvastatin Alone.
** An additional regression was noted in patients treated with ENC for 24 months.
||A Phase 3, Double-Blind, Randomized, Multisite Trial Of The Efficacy, Safety, And Tolerability Of The Fixed Combination Torcetrapib/Atorvastatin Administered Orally, Once Daily For 12 Months, Compared To Atorvastatin Alone, Titrated Based On NCEP ATP-III LDL-C Goals In Subjects With Fredrickson Types IIa And IIb Dyslipidemias  || Completed || NCT00137462
** Changes in HDL-C were independently associated with regression of CIMT, controlling for changes in LDL and triglycerides.
||  Torcetrapib||3
* CONCLUSION: ERN when added to statin therapy significantly increases HDL levels and induces [[atherosclerosis]] regression. Open label design and the inability to correlate CIMT effects to clinical outcomes were the limitations of this study.
|-
|  Carotid B-Mode Ultrasound Study to Compare Anti-Atherosclerotic Effect of Torcetrpib/Atorvastatin to Atorvastatin Alone. (RADIANCE 1)
||  Phase 3 Multi-Center, Double-Blind, Randomized, Parallel Group, Carotid B-Mode Ultrasound Evaluation of the Anti-Atherosclerotic Efficacy, Safety and Tolerability of Fixed Combination CP-529,414/Atorvastatin, Administered Orally, Once Daily (QD) for 24 Months, Compared With Maximally Tolerated Atorvastatin Therapy Alone, in Subjects With Heterozygous Familial Hypercholesterolemia.||Completed  || NCT00136981||  Torcetrapib|| 3
|-


===ARBITER 6-HALTS Trial<ref name="pmid19915217">{{cite journal |author=Taylor AJ, Villines TC, Stanek EJ, ''et al.'' |title=Extended-release niacin or ezetimibe and carotid intima-media thickness |journal=[[The New England Journal of Medicine]] |volume=361 |issue=22 |pages=2113–22 |year=2009 |month=November|pmid=19915217 |doi=10.1056/NEJMoa0907569 |url=}}</ref><ref name="pmid20399059">{{cite journal |author=Villines TC, Stanek EJ, Devine PJ, ''et al.'' |title=The ARBITER 6-HALTS Trial (Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 6-HDL and LDL Treatment Strategies in Atherosclerosis): final results and the impact of medication adherence, dose, and treatment duration |journal=[[Journal of the American College of Cardiology]]|volume=55 |issue=24 |pages=2721–6 |year=2010 |month=June |pmid=20399059 |doi=10.1016/j.jacc.2010.03.017 |url=}}</ref>===
* OBJECTIVES: To study the effects of extended-release [[niacin]] or [[ezetimibe]] added to [[statin]] monotherapy on [[carotid intima-media thickness]].
* METHOD: Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 6-HDL and LDL Treatment Strategies in Atherosclerosis (ARBITER 6-HALTS) trial was an open labeled randomized trial. The study subjects consisted of patients who had [[coronary artery disease]] or equivalent on long standing [[statin]] therapy with [[LDL]] cholesterol levels above 100 mg/dl and [[HDL]] cholesterol levels below 50 mg/dl for men and 55 mg/dl in women. The patients were randomly assigned to extended-release [[niacin]] (target dose 2000 mg) or [[ezetimibe]] (10 mg daily). The primary end point was a change in the [[carotid intima-media thickness]] from baseline in both study groups. This trial was terminated early because of side-effects of the drugs which affected compliance.
* RESULTS:
** A significant increase in [[HDL]] levels, and a decrease in [[LDL]] and [[triglyceride]] levels was noted in the [[niacin]] group.
** [[Niacin]] group showed a significant change in terms of [[CMIT]], leading to a reduction in both mean and maximal carotid intima-media thickness.
** A paradoxical increase in the [[CMIT ]] was noted along with a reduction in [[LDL]] levels in the [[ezetimibe]] group. There was also a fall in both [[HDL]] and [[triglyceride]] levels.
* CONCLUSION: Extended release [[niacin]] causes statistically significant reduction in the [[carotid intima-media thickness]] and is superior to [[ezetimibe]].


===CLAS Trial<ref name="pmid2243429">{{cite journal |author=Cashin-Hemphill L, Mack WJ, Pogoda JM, Sanmarco ME, Azen SP, Blankenhorn DH |title=Beneficial effects of colestipol-niacin on coronary atherosclerosis. A 4-year follow-up |journal=JAMA |volume=264 |issue=23 |pages=3013–7 |year=1990 |month=December |pmid=2243429 |doi= |url=}}</ref><ref name="pmid8616937">{{cite journal |author=Azen SP, Mack WJ, Cashin-Hemphill L, ''et al.'' |title=Progression of coronary artery disease predicts clinical coronary events. Long-term follow-up from the Cholesterol Lowering Atherosclerosis Study |journal=Circulation |volume=93 |issue=1 |pages=34–41 |year=1996 |month=January |pmid=8616937 |doi= |url=}}</ref><ref name="pmid3327654">{{cite journal |author=Blankenhorn DH, Johnson RL, Nessim SA, Azen SP, Sanmarco ME, Selzer RH |title=The Cholesterol Lowering Atherosclerosis Study (CLAS): design, methods, and baseline results |journal=Control Clin Trials |volume=8 |issue=4 |pages=356–87 |year=1987 |month=December |pmid=3327654 |doi= |url=}}</ref><ref name="pmid1991366">{{cite journal |author=Blankenhorn DH, Azen SP, Crawford DW, ''et al.'' |title=Effects of colestipol-niacin therapy on human femoral atherosclerosis |journal=Circulation |volume=83 |issue=2 |pages=438–47 |year=1991 |month=February |pmid=1991366 |doi= |url=}}</ref>===
|}
* OBJECTIVE: To determine whether combined therapy with the [[lipid]] lowering agents [[colestipol]] hydrochloride plus niacin would produce significant change in coronary, carotid, and [[femoral artery]] [[atherosclerosis]] and coronary bypass [[graft]] lesions as determined by [[angiography]]. Also, to determine possible correlations between lesion changes and plasma lipid and [[lipoprotein]] [[cholesterol]] levels and to explore interrelationships of atherosclerosis change in femoral, coronary, and [[carotid arteries]].
* METHOD: CLAS (Cholesterol Lowering Atherosclerosis Study) was a randomized, selectively blinded study wherein 188 men, with known previous [[coronary artery bypass graft]]s, were randomized to diet plus placebo or diet plus combined lipid lowering therapy consisting of colestipol and [[niacin]] and followed up at 2 years and 4 years.
* RESULTS: The following results were noted:<ref name="pmid3295315">{{cite journal |author=Blankenhorn DH, Nessim SA, Johnson RL, Sanmarco ME, Azen SP, Cashin-Hemphill L |title=Beneficial effects of combined colestipol-niacin therapy on coronary atherosclerosis and coronary venous bypass grafts |journal=JAMA |volume=257 |issue=23 |pages=3233–40 |year=1987 |month=June |pmid=3295315 |doi= |url=}}</ref>
** Treatment group had a 37% raise in HDL-C levels and a 43% reduction in LDL-C levels.
** Regression of atherosclerosis, as measured by angiography, was greater with combined drug treatment at 2 years and at 4 years.
** Reduction in the percentage of subjects with new [[atheroma]] formation in native coronary arteries.
** Significantly reduced percentage of subjects with new lesions or any adverse change in bypass grafts.
** Atherosclerosis regression occurred in 16.2% of colestipol-niacin treated vs 2.4% placebo treated
* CONCLUSION: The benefit of combined nicotinic acid and colestipol therapy was most prominent in patients with baseline plasma cholesterol levels above 240 mg/dL.


===FATS Trial<ref name="pmid2215615">{{cite journal |author=Brown G, Albers JJ, Fisher LD, ''et al.'' |title=Regression of coronary artery disease as a result of intensive lipid-lowering therapy in men with high levels of apolipoprotein B |journal=N. Engl. J. Med. |volume=323 |issue=19 |pages=1289–98 |year=1990 |month=November |pmid=2215615 |doi=10.1056/NEJM199011083231901 |url=}}</ref><ref name="pmid8252687">{{cite journal |author=Zhao XQ, Brown BG, Hillger L, ''et al.'' |title=Effects of intensive lipid-lowering therapy on the coronary arteries of asymptomatic subjects with elevated apolipoprotein B |journal=Circulation |volume=88 |issue=6 |pages=2744–53 |year=1993 |month=December |pmid=8252687 |doi= |url=}}</ref><ref name="pmid23168285">{{cite journal |author=Phan BA, Muñoz L, Shadzi P, ''et al.'' |title=Effects of niacin on glucose levels, coronary stenosis progression, and clinical events in subjects with normal baseline glucose levels (<100 mg/dl): a combined analysis of the Familial Atherosclerosis Treatment Study (FATS), HDL-Atherosclerosis Treatment Study (HATS), Armed Forces Regression Study (AFREGS), and Carotid Plaque Composition by MRI during lipid-lowering (CPC) study |journal=Am. J. Cardiol. |volume=111 |issue=3 |pages=352–5 |year=2013 |month=February |pmid=23168285 |doi=10.1016/j.amjcard.2012.09.034 |url=}}</ref><ref name="pmid8106695">{{cite journal |author=Stewart BF, Brown BG, Zhao XQ, ''et al.'' |title=Benefits of lipid-lowering therapy in men with elevated apolipoprotein B are not confined to those with very high low density lipoprotein cholesterol |journal=J. Am. Coll. Cardiol. |volume=23 |issue=4 |pages=899–906 |year=1994 |month=March |pmid=8106695 |doi= |url=}}</ref><ref name="pmid7695184">{{cite journal |author=Brown BG, Hillger L, Zhao XQ, Poulin D, Albers JJ |title=Types of change in coronary stenosis severity and their relative importance in overall progression and regression of coronary disease. Observations from the FATS Trial. Familial Atherosclerosis Treatment Study |journal=Ann. N. Y. Acad. Sci. |volume=748 |issue= |pages=407–17; discussion 417–8 |year=1995 |month=January |pmid=7695184 |doi= |url=}}</ref><ref name="pmid7500507">{{cite journal |author=Maher VM, Brown BG, Marcovina SM, Hillger LA, Zhao XQ, Albers JJ |title=Effects of lowering elevated LDL cholesterol on the cardiovascular risk of lipoprotein(a) |journal=JAMA |volume=274 |issue=22 |pages=1771–4 |year=1995 |month=December |pmid=7500507 |doi= |url=}}</ref><ref name="pmid10208998">{{cite journal |author=Zambon A, Hokanson JE, Brown BG, Brunzell JD |title=Evidence for a new pathophysiological mechanism for coronary artery disease regression: hepatic lipase-mediated changes in LDL density |journal=Circulation |volume=99 |issue=15 |pages=1959–64 |year=1999 |month=April |pmid=10208998 |doi= |url=}}</ref>===
==Niacin==
* OBJECTIVE: To compare the effects of two intensive [[lipid]] altering therapies in men with [[familial combined hyperlipidemia]] as assessed by [[arteriography]].
{| class="wikitable sortable" style="font-size:90%"
* METHOD: Familial Atherosclerosis Treatment Study (FATS) is a randomized, double blinded, [[placebo]] controlled study wherein 146 men with one coronary [[stenosis]] of greater than 50 percent or three lesions of greater than 30 percent were enrolled and randomized into three groups. The groups included:
! '''Name of the Trial'''
** Placebo plus low dose [[colestipol]] (if needed, to lower [[LDL]])
! '''Official Title'''
** [[Niacin]] (1 g QID) plus colestipol (10 g TID)
! '''Status'''
** [[Lovastatin]] (20 mg BID) plus colestipol (10 g TID)
! '''ClinicalTrials.gov Identifier'''
The primary endpoint was a measure of change in the severity of disease in the proximal coronary arteries as measured by quantitative arteriography.
! '''Drug name'''
* RESULTS: Both the intensive lipid lowering therapies were equally effective. Both reduced the frequency of progression of coronary lesions (21% and 25% versus 46% in the control group), increased the frequency of regression (32% and 39% versus 11%), and reduced the incidence of cardiovascular events in men with coronary artery disease who were at high risk for cardiovascular events.
! '''Trial phase'''
|-
| Niacin Plus Statin to Prevent Vascular Events ([[AIM-HIGH Trial]])||AIM HIGH: Niacin Plus Statin to Prevent Vascular Events ||Terminated ||NCT00120289||Niacin || Phase 3
|-
| Carotid Plaque Characteristics by MRI in AIM-HIGH (Carotid MRI Substudy) ([[AIM-HIGH Trial]])|| Carotid Plaque Characteristics by MRI in AIM-HIGH|| Ongoing||NCT01178320||Simvastatin +Niacin|| Observational
|-
| Plaque Inflammation and Dysfunctional HDL Cholesterol in Participants Receiving Niacin and Statins in the AIM-HIGH Study (The HDL Proteomics Study) ([[AIM-HIGH Trial]])||Plaque Inflammation and Dysfunctional HDL in AIM-HIGH|| Completed ||NCT00880178||Simvastatin +Niacin||Observational
|-
| [[ARBITER 2 Trial]] || || || || ||  
|-
| [[ARBITER 3 Trial]] || || || || ||  
|-
|Comparative Study of the Effect of Ezetimibe Versus Extended-Release Niacin on Atherosclerosis ([[ARBITER 6-HALTS Trial]]) ||ARBITER 6: ARterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 6 - HDL and LDL Treatment Strategies in Atherosclerosis (HALTS)|| Terminated ||NCT00397657 ||Ezetimibe, Niacin || Phase 4
|-
| [[CLAS Trial]] || || || || ||  
|-
| HDL-Atherosclerosis Treatment Study ([[HATS]])||HDL-Atherosclerosis Treatment Study ([[HATS]])||Completed||NCT00000553 ||Simvastatin, Niacin, Antioxidants || Phase 3
|-
| [[Oxford Niaspan Study]] ||Oxford Niaspan Study: Effects of Niaspan on Atherosclerosis and Endothelial Function||Cardiovascular Magnetic Resonance Evaluation of the Effects of Niaspan on Regression of Atherosclerosis and Restoration of Endothelial Function||Unknown||NCT00232531|| Interventional (study phase not provided)
|-
|}


===REGRESS Trial<ref name="pmid7743614">{{cite journal |author=Jukema JW, Bruschke AV, van Boven AJ, ''et al.'' |title=Effects of lipid lowering by pravastatin on progression and regression of coronary artery disease in symptomatic men with normal to moderately elevated serum cholesterol levels. The Regression Growth Evaluation Statin Study (REGRESS) |journal=Circulation |volume=91 |issue=10 |pages=2528–40 |year=1995 |month=May |pmid=7743614 |doi= |url=}}</ref><ref name="pmid8840836">{{cite journal |author=van Boven AJ, Jukema JW, Zwinderman AH, Crijns HJ, Lie KI, Bruschke AV |title=Reduction of transient myocardial ischemia with pravastatin in addition to the conventional treatment in patients with angina pectoris. REGRESS Study Group |journal=Circulation |volume=94 |issue=7 |pages=1503–5 |year=1996 |month=October |pmid=8840836 |doi= |url=}}</ref><ref name="pmid11018193">{{cite journal |author=Mulder HJ, Bal ET, Jukema JW, ''et al.'' |title=Pravastatin reduces restenosis two years after percutaneous transluminal coronary angioplasty (REGRESS trial) |journal=Am. J. Cardiol. |volume=86 |issue=7 |pages=742–6 |year=2000 |month=October |pmid=11018193 |doi= |url=}}</ref><ref name="pmid1486543">{{cite journal |author=Barth JD, Zonjee MM |title=Regression growth evaluation statin study (REGRESS): study design and baseline characteristics in 600 patients. The REGRESS Research Group |journal=Can J Cardiol |volume=8 |issue=9 |pages=925–32 |year=1992 |month=November |pmid=1486543 |doi= |url=}}</ref>===
==Fibrate==
* OBJECTIVE: To evaluate the effects of [[cholesterol]] lowering therapy, using a hydroxymethyl glutaryl coenzyme A reductase inhibitor ([[pravastatin]]) in symptomatic men with [[coronary artery disease]] ([[CAD]]).
{| style="font-size:120%"
* METHOD: Regression Growth Evaluation Statin Study (REGRESS) was a multicentered, prospective, double-blinded, randomized, placebo-controlled trial that enrolled 885 men with established coronary artery disease with total cholesterol levels in the range of 155 and 310 mg/dL. The patients were randomized into two groups, treatment and control and followed up for two years. Effect of pravastatin on progression and regression of coronary atherosclerosis was assessed by quantitative [[coronary arteriography]]. All the patients received routine antianginal treatment for the duration of the trial.
|-
* RESULTS: Percent diameter stenosis before angioplasty was 78 +/- 14% (mean +/- SD) in the pravastatin group and 80 +/- 14% in the placebo group (p = 0.46). At follow-up, the percent diameter [[stenosis]] was 32 +/- 23% in the pravastatin group and 45 +/- 29% in the [[placebo]] group (p < 0.001). Clinical restenosis was significantly lower in the pravastatin group (7%) compared with the placebo group (29%) (p < 0.001).
| [[VA-HIT Trial]]
* CONCLUSION: In symptomatic men with significant coronary artery disease and normal to moderately elevated serum cholesterol, less progression of coronary atherosclerosis and fewer new cardiovascular events were observed in the group of patients treated with pravastatin than in the placebo group.
|-
| [[BECAIT Trial]]
|-
| [[BIP Trial]]
|-
|}


===BECAIT Trial<ref name="pmid9822092">{{cite journal |author=Ruotolo G, Ericsson CG, Tettamanti C, ''et al.'' |title=Treatment effects on serum lipoprotein lipids, apolipoproteins and low density lipoprotein particle size and relationships of lipoprotein variables to progression of coronary artery disease in the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) |journal=J. Am. Coll. Cardiol. |volume=32 |issue=6 |pages=1648–56 |year=1998 |month=November |pmid=9822092 |doi= |url=}}</ref><ref name="pmid7555614">{{cite journal |author=de Faire U, Ericsson CG, Hamsten A, Nilsson J |title=Design features of a five-year Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) |journal=Drugs Exp Clin Res |volume=21 |issue=3 |pages=105–24 |year=1995 |pmid=7555614 |doi= |url=}}</ref><ref name="pmid8622389">{{cite journal |author=Ericsson CG, Hamsten A, Nilsson J, Grip L, Svane B, de Faire U |title=Angiographic assessment of effects of bezafibrate on progression of coronary artery disease in young male postinfarction patients |journal=Lancet |volume=347 |issue=9005 |pages=849–53 |year=1996 |month=March |pmid=8622389 |doi= |url=}}</ref><ref name="pmid9717064">{{cite journal |author=Ericsson CG |title=Results of the Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) and an update on trials now in progress |journal=Eur. Heart J. |volume=19 Suppl H |issue= |pages=H37–41 |year=1998 |month=July |pmid=9717064 |doi= |url=}}</ref>===
==Statin==
* OBJECTIVE: To evaluate if bezafibrate could slow the progression of coronary stenoses in dyslipidemic male survivors of myocardial infarction who were younger than 45 years at the time of the event.
{| style="font-size:120%"
* METHOD: The Bezafibrate Coronary Atherosclerosis Intervention Trial (BECAIT) was a randomized, double-blinded, placebo-controlled trial over 5 years to assess the angiographic benefits of bezafibrate retard (400 mg a day) in 92 young (45 yrs), male, post-[[myocardial infarction]] (post-MI) patients with [[dyslipidemia]] (fasting serum [[cholesterol]] concentration above 240 mg/dL and [[triglyceride]] concentration above 141 mg/dL).
|-
* RESULTS:
| [[ASTEROID Trial]]
** [[Bezafibrate]] reduced the levels of LDL-C and triglycerides by 53% and 46% respectively
|-
** Plasma apolipoprotein (apo) B levels reduced by 9%
| [[SATURN Trial]]
** [[HDL]]3 levels rose by 9%
|-
* CONCLUSION: The effect of bezafibrate on progression of focal coronary atherosclerosis could be at least partly attributed to a rise in HDL3 cholesterol and a decrease in the total number of apo B-containing lipoproteins. Treatment with bezafibrate also significantly reduced the levels of [[insulin-like growth factor]] (IGF-1) which is one other factor associated with disease progression.
| [[4S Trial]]
|-
| [[CORONA Trial]]
|-
|}


===GAIN Trial<ref name="pmid11468198">{{cite journal |author=Schartl M, Bocksch W, Koschyk DH, ''et al.'' |title=Use of intravascular ultrasound to compare effects of different strategies of lipid-lowering therapy on plaque volume and composition in patients with coronary artery disease |journal=[[Circulation]] |volume=104 |issue=4 |pages=387–92 |year=2001 |month=July |pmid=11468198 |doi= |url=}}</ref>===
==Multiple Lipid Lowering Drugs==
* GAIN trial studied the effects of [[atorvastatin]] on the progression of atherosclerosis, assessed by intra-coronary ultrasound ([[IVUS]]) in 131 patients.
{| style="font-size:120%"
* After a 12 month follow-up period, it was found that atorvastatin reduced the progression of mean [[plaque]] volume (1.2 versus 9.6 mm<sup>3</sup> for placebo). Also, the drug increased hyperechogenicity of the plaque which indicates a change in plaque composition from lipid-rich core to fibrotic or calcified. This change in composition of the plaque corresponds to increased plaque stability and a reduced tendency for rupture.
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| [[HARP Study]]
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| [[AFREGS Trial]]
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===HARP Study<ref name="pmid7934538">{{cite journal |author=Sacks FM, Pasternak RC, Gibson CM, Rosner B, Stone PH |title=Effect on coronary atherosclerosis of decrease in plasma cholesterol concentrations in normocholesterolaemic patients. Harvard Atherosclerosis Reversibility Project (HARP) Group |journal=Lancet |volume=344 |issue=8931 |pages=1182–6 |year=1994 |month=October |pmid=7934538 |doi= |url=}}</ref><ref name="pmid7759696">{{cite journal |author=Sacks FM, Stone PH, Gibson CM, Silverman DI, Rosner B, Pasternak RC |title=Controlled trial of fish oil for regression of human coronary atherosclerosis. HARP Research Group |journal=J. Am. Coll. Cardiol. |volume=25 |issue=7 |pages=1492–8 |year=1995 |month=June |pmid=7759696 |doi= |url=}}</ref><ref name="pmid7572692">{{cite journal |author=Sacks FM, Gibson CM, Rosner B, Pasternak RC, Stone PH |title=The influence of pretreatment low density lipoprotein cholesterol concentrations on the effect of hypocholesterolemic therapy on coronary atherosclerosis in angiographic trials. Harvard Atherosclerosis Reversibility Project Research Group |journal=Am. J. Cardiol. |volume=76 |issue=9 |pages=78C–85C |year=1995 |month=September |pmid=7572692 |doi= |url=}}</ref><ref name="pmid8815751">{{cite journal |author=Pasternak RC, Brown LE, Stone PH, Silverman DI, Gibson CM, Sacks FM |title=Effect of combination therapy with lipid-reducing drugs in patients with coronary heart disease and "normal" cholesterol levels. A randomized, placebo-controlled trial. Harvard Atherosclerosis Reversibility Project (HARP) Study Group |journal=Ann. Intern. Med. |volume=125 |issue=7 |pages=529–40 |year=1996 |month=October |pmid=8815751 |doi= |url=}}</ref>===
* OBJECTIVE: The Harvard Atherosclerosis Reversibility Project (HARP) aimed at studying the effect of intensive lipid lowering therapy in normocholesterolemic patients and its effect on angiographic progression of [[atherosclerosis]].
* METHOD: HARP was a randomized placebo-controlled trial wherein 91 normocholesterolemic patients, with total serum [[cholesterol]] levels less than 250 mg/dL, were selected and treated with a stepwise regimen of diet, [[pravastatin]], [[nicotinic acid]], [[cholestyramine]] and [[gemfibrozil]] for 2.5 years. Repeat coronary angiograms were performed to assess the progression of coronary atherosclerosis.
* RESULTS: The study found a significant improvement in total cholesterol, [[LDL]]-C and [[HDL]]-C levels, however repeat [[coronary angiogram]]s did not show significant differences in the degree of coronary obstruction, progression of coronary stenosis, regression and clinical cardiac events.
* CONCLUSION: This study concluded that intensive lipid lowering therapy does not alter the rate of progression of coronary stenoses in normocholesterolemic patients.


===SCAT Trial<ref name="pmid11023927">{{cite journal |author=Teo KK, Burton JR, Buller CE, ''et al.'' |title=Long-term effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis: The Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT) |journal=Circulation |volume=102 |issue=15 |pages=1748–54 |year=2000 |month=October |pmid=11023927 |doi= |url=}}</ref><ref name="pmid1271748">{{cite journal |author=Crawford DW, Barndt R, Back LH |title=Surface characteristics of normal and atherosclerotic human arteries including observations suggesting interaction between flow and intimal morphology |journal=Lab. Invest. |volume=34 |issue=5 |pages=463–70 |year=1976 |month=May |pmid=1271748 |doi= |url=}}</ref><ref name="pmid9215232">{{cite journal |author=Teo KK, Burton JR, Buller C, Plante S, Yokoyama S, Montague TJ |title=Rationale and design features of a clinical trial examining the effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary atherosclerosis: Simvastatin/Enalapril Coronary Atherosclerosis Trial (SCAT). SCAT Investigators |journal=Can J Cardiol |volume=13 |issue=6 |pages=591–9 |year=1997 |month=June |pmid=9215232 |doi= |url=}}</ref>===
{{Lipopedia}}
* OBJECTIVE: To assess the effects of cholesterol lowering and angiotensin-converting enzyme inhibition on coronary [[atherosclerosis]] in normocholesterolemic patients.
* METHOD: The [[Simvastatin]]/[[Enalapril]] Coronary Atherosclerosis Trial (SCAT) was a multicentered, randomized, double blinded, placebo-controlled angiographic trial wherein a total of 460 normocholesterolemic patients were enrolled. 230 received simvastatin, 230 a simvastatin placebo, 229 enalapril and 231 an enalapril placebo. All the patients were followed up for an average time period of 47.8 months.
* RESULTS and CONCLUSION: Less progression was observed in patients receiving simvastatin compared to those receiving [[placebo]]. On quantitative coronary angiography the change in mean diameter, minimum diameter, percentage [[stenosis]] and the need for angioplasty was less with simvastatin. No additional benefit was observed with enalapril therapy.
 
===REVERSAL Trial<ref name="urlEffect of intensive compared with moderate lipid-loweri... [JAMA. 2004] - PubMed - NCBI">{{cite web |url=http://www.ncbi.nlm.nih.gov/pubmed/14996776?dopt=Abstract |title=Effect of intensive compared with moderate lipid-loweri... [JAMA. 2004] - PubMed - NCBI |format= |work= |accessdate=}}</ref>===
* OBJECTIVE: To compare the effects of pravastatin and atorvastatin on coronary artery plaque burden and progression by intensive lipid lowering.
* METHOD: Reversal of Atherosclerosis with Aggressive Lipid Lowering [REVERSAL] was a multicentered, randomized, double- blinded trial wherein 654 patients received the study drug. IVUS examinations were performed at baseline and after 18 months of treatment in 502 patients. Patients randomly received either 40 mg pravastatin or 80 mg of atorvastatin.
* RESULTS: The mean LDL-C levels reduced from 150 to 110 mg/dL in the pravastatin group and to 79 mg/dL in the atorvastatin. Percentage change in atheroma volume showed a significantly lower progression rate in the atorvastatin (intensive) group compared to the pravastatin group.
* CONCLUSION: In patients with coronary artery disease, [[atorvastatin]] reduced progression of coronary atherosclerosis compared with [[pravastatin]].
 
===ASTEROID Trial<ref name="urlEffect of very high-intensity statin therapy on regress... [JAMA. 2006] - PubMed - NCBI">{{cite web |url=http://www.ncbi.nlm.nih.gov/pubmed/16533939 |title=Effect of very high-intensity statin therapy on regress... [JAMA. 2006] - PubMed - NCBI |format= |work= |accessdate=}}</ref>===
* OBJECTIVE: To assess if an extensive lipid lowering therapy with [[statin]]s could regress coronary [[atherosclerosis]] as determined by [[IVUS]] imaging.
* METHOD: A Study to Evaluate the Effect of Rosuvastatin on Intravascular Ultrasound-Derived Coronary Atheroma Burden (ASTEROID) was a prospective open-label blinded end-points trial wherein 507 patients, who had a baseline IVUS examination, received at least 1 dose of the study drug [[rosuvastatin]] 40 mg/dL and were followed up for 24 months. At the end of 24 months 349 patients had evaluable serial IVUS examinations.
* RESULTS: Mean baseline [[LDL]]-C reduced by 53.2% and mean HDL-C improved by 14.7%. Also mean [[atheroma]] volume for the entire vessel, as assessed by intravascular ultrasound, reduced by 0.98%.
* CONCLUSION: The study showed that treatment with very high intensity statin therapy using rosuvastatin 40 mg/dL reduced LDL-C and improved HDL-C levels significantly resulting in regression of coronary atherosclerosis as measured by IVUS.
 
===Oxford Niaspan Study<ref name="urlEffects of high-dose modified-release nico... [J Am Coll Cardiol. 2009] - PubMed - NCBI">{{cite web |url=http://www.ncbi.nlm.nih.gov/pubmed/19874992?dopt=Abstract |title=Effects of high-dose modified-release nico... [J Am Coll Cardiol. 2009] - PubMed - NCBI |format= |work= |accessdate=}}</ref>===
* OBJECTIVE: To assess the effects of high dose niacin on the progression of atherosclerosis.
* METHOD: Oxford Niaspan study was a double blinded, randomized, placebo-controlled study of 2 g daily modified-release in 71 patients with HDL-C levels less than 40 mg/dL and either: 1) type 2 [[diabetes]] with coronary heart disease; or 2) carotid/peripheral atherosclerosis. All the patients were on an additional statin therapy. The change in carotid artery wall area was assessed by magnetic resonance imaging after 1 year.
* RESULTS: Niacin increased HDL-C by 23% and reduced low-density lipoprotein cholesterol by 19% and at 12 months niacin significantly reduced carotid wall area compared with placebo.
* CONCLUSION: Compared with placebo, treatment with high-dose modified-release niacin along with statin therapy significantly reduced carotid atherosclerosis within 12 months.
 
===SATURN Trial===
* OBJECTIVE: To compare the effects of two intensive lipid lowering treatment regimens (statins) on the progression of coronary atherosclerosis and to assess their safety and side-effect profiles.
* METHOD: Study of Coronary Atheroma by Intravascular Ultrasound: Effect of Rosuvastatin Versus Atorvastatin (SATURN) trial was a randomized trial which enrolled 1049 patients with known coronary artery disease, to study the effects of rosuvastatin and atorvastatin on the progression of coronary atherosclerosis. Percent atheroma volume and total atheroma volume were assessed by intravascular ultrasound (IVUS) at baseline and after 104 weeks of treatment with either [[rosuvastatin]] 40 daily and [[atorvastatin]] 80 mg daily.
* RESULTS: At the end of 104 weeks:
** Serum LDL-C levels were lower in the rosuvastatin group than atorvastatin group.
** Similarly serum HDL-C levels were higher in the rosuvastatin group than in atorvastatin group.
** Percent atheroma volume (PAV), decreased by 0.99% with atorvastatin and by 1.22% with rosuvastatin.
* CONCLUSION: Maximal doses of rosuvastatin and atorvastatin resulted in significant regression of coronary atherosclerosis. Even though rosuvastatin achieved a lower LDL-C and higher HDL-C levels compared to atorvastatin, a similar degree of regression of PAV was observed in both the treatment groups.
 
===4S Trial<ref name="pmid7968073">{{cite journal |author= |title=Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S) |journal=Lancet |volume=344 |issue=8934 |pages=1383–9 |year=1994 |month=November |pmid=7968073 |doi= |url=}}</ref>===
* OBJECTIVE: To evaluate the effect of cholesterol lowering with simvastatin on mortality and morbidity in patients with [[coronary artery disease]] (CAD).
* METHOD: The Scandinavian Simvastatin Survival Study (4S) enrolled 4444 patients with known CAD ([[angina pectoris]] or previous [[myocardial infarction]]) and serum cholesterol  levels between 212 and 309 mg/dL. Patients were randomly assigned to either [[simvastatin]] (20 to 40 mg/day) or [[placebo]] and were followed-up for a median period of 5.4 years.
* RESULTS:
** Total cholesterol reduced by 25%
** LDL-C levels reduced by 35%
** Mean HDL-C improved by 8%
** [[Mortality]] rate was lower in the simvastatin group compared with that in the placebo group (8% vs 12%)
** Significant reductions in major coronary events (19 versus 28 percent)
* CONCLUSION: The study showed that long-term treatment with simvastatin is safe and improves survival in CAD patients.
 
===LIPID Study<ref name="pmid9841303">{{cite journal |author= |title=Prevention of cardiovascular events and death with pravastatin in patients with coronary heart disease and a broad range of initial cholesterol levels. The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) Study Group |journal=[[The New England Journal of Medicine]] |volume=339 |issue=19 |pages=1349–57 |year=1998 |month=November |pmid=9841303 |doi=10.1056/NEJM199811053391902 |url=}}</ref>===
* OBJECTIVE: To assess the efficacy of [[pravastatin]] in reducing mortality in known CAD patients.
* METHOD: The Long-Term Intervention with Pravastatin in Ischaemic Disease (LIPID) study was a randomized, double-blinded, placebo controlled trial wherein 9014 patients (young and old) with known CAD and total cholesterol levels in the range of 155 to 271 mg per deciliter were enrolled and randomly assigned to treatment with either 40 mg daily pravastatin or placebo. The patients were followed up for a mean period of 6.1 years.
* RESULTS:
** Pravastatin was associated with a lower rate of death from CAD compared with placebo (6.4% vs 8.3%)
** Overall mortality rate was lower in the pravastatin group compared with that in the placebo group (11% vs 14.1%)
** The incidence of all cardiovascular outcomes was consistently lower among patients assigned to receive pravastatin
* CONCLUSION: Treatment with pravastatin reduced mortality from coronary heart disease and overall mortality, as compared with the rates in the placebo group, as well as the incidence of all prespecified cardiovascular events in patients with a history of myocardial infarction or [[unstable angina]] who had a broad range of initial cholesterol levels.
 
===TNT Trial<ref name="pmid19410683">{{cite journal |author=Waters DD |title=Clinical insights from the Treating to New Targets trial |journal=[[Progress in Cardiovascular Diseases]] |volume=51 |issue=6 |pages=487–502 |year=2009 |pmid=19410683 |doi=10.1016/j.pcad.2009.01.001 |url=}}</ref>===
* OBJECTIVE: To compare the efficacy of 10 mg and 80 mg daily dose of [[atorvastatin]] in patients with stable CAD and baseline LDL-C between 130 mg/dL and 250 mg/dL.
* METHOD: The Treating to New Targets (TNT) trial was a randomized trial that enrolled 10,001 patients with stable coronary artery disease to treatment with atorvastatin, 80 or 10 mg/dL, and followed them up for a median period of 4.9 years. The primary end point was a composite of cardiovascular death, [[myocardial infarction]], resuscitated cardiac arrest, and [[stroke]].
* RESULTS: Compared to low dose, high dose atorvastatin was associated with:
** A significantly lower mean serum LDL-C concentration (77 vs 101 mg/dL)
** Significant reductions in the rate of the primary end point (8.7 vs 10.9 percent)
** No reduction in all-cause mortality. Higher doses of atorvastatin, although reduced mortality due to cardiac events, were associated with higher mortality rate due to noncardiovascular events.
* CONCLUSION: Wider use of the 80-mg dose of atorvastatin in patients with stable coronary disease is safe, cost-effective, and provides an incremental reduction in coronary events.
 
===IDEAL Trial<ref name="pmid16287954">{{cite journal |author=Pedersen TR, Faergeman O, Kastelein JJ, ''et al.'' |title=High-dose atorvastatin vs usual-dose simvastatin for secondary prevention after myocardial infarction: the IDEAL study: a randomized controlled trial |journal=[[JAMA : the Journal of the American Medical Association]] |volume=294 |issue=19 |pages=2437–45 |year=2005 |month=November |pmid=16287954 |doi=10.1001/jama.294.19.2437 |url=}}</ref><ref name="pmid20643245">{{cite journal |author=Pedersen TR, Cater NB, Faergeman O, ''et al.'' |title=Comparison of atorvastatin 80 mg/day versus simvastatin 20 to 40 mg/day on frequency of cardiovascular events late (five years) after acute myocardial infarction (from the Incremental Decrease in End Points through Aggressive Lipid Lowering [IDEAL] trial) |journal=[[The American Journal of Cardiology]] |volume=106 |issue=3 |pages=354–9 |year=2010 |month=August |pmid=20643245 |doi=10.1016/j.amjcard.2010.03.033 |url=}}</ref>===
* OBJECTIVE: To compare the effects of two lipid lowering strategies (high dose [[atorvastatin]] [80 mg] and [[simvastatin]] 20 mg) on the risk of cardiovascular disease among patients with a previous myocardial infarction (MI).
* METHOD: The Incremental Decrease in End Points through Aggressive Lipid Lowering (IDEAL) trial was a prospective, randomized, open-label, blinded end-point evaluation trial which enrolled 8888 patients with past history of acute myocardial infarction, who were randomly assigned to treatment with high dose atorvastatin (80 mg) or simvastatin 20 mg. The primary endpoint was a major coronary event, defined as coronary death, confirmed nonfatal acute MI, or [[cardiac arrest]] with [[resuscitation]].
* RESULTS: After a median follow-up time of 4.8 years, compared with patients in simvastatin group those in atorvastatin group were associated with:
** Lower mean LDL-C levels (81 vs 104 mg/dL)
** Lowered primary end point rate (9.3% vs 10.4%)
** Lowered occurrence of any coronary event (898 vs 1059)
* CONCLUSION: Intensive lowering of LDL-C did not result in a significant reduction in the primary outcome of major coronary events, but did reduce the risk of other composite secondary end points and nonfatal acute MI. There were no differences in cardiovascular or all-cause mortality.
 
===SEARCH Study<ref name="pmid21067805">{{cite journal |author=Armitage J, Bowman L, Wallendszus K, ''et al.'' |title=Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial |journal=[[Lancet]] |volume=376 |issue=9753 |pages=1658–69 |year=2010 |month=November |pmid=21067805 |pmc=2988223 |doi=10.1016/S0140-6736(10)60310-8 |url=}}</ref><ref name="pmid17967584">{{cite journal |author=Bowman L, Armitage J, Bulbulia R, Parish S, Collins R |title=Study of the effectiveness of additional reductions in cholesterol and homocysteine (SEARCH): characteristics of a randomized trial among 12064 myocardial infarction survivors |journal=[[American Heart Journal]] |volume=154 |issue=5 |pages=815–23, 823.e1–6 |year=2007 |month=November |pmid=17967584 |doi=10.1016/j.ahj.2007.06.034 |url=}}</ref>===
* OBJECTIVE: To study the efficacy and safety of prolonged use of more intensive cholesterol-lowering therapy in patients at high cardiovascular risk.
* METHOD: Study of the effectiveness of additional reductions in [[cholesterol]] and [[homocysteine]] (SEARCH) was a randomized, double blinded study which enrolled 12,064 men and women aged 18-80 years with a history of myocardial infarction. In addition these patients were randomly assigned to [[homocysteine]] lowering with [[folic acid]] 2 mg plus [[Vitamin B12|vitamin B<sub>12</sub>]] 1 mg daily versus matching placebo. The primary endpoint was major vascular events, defined as coronary death, [[myocardial infarction]], [[stroke]], or arterial revascularization.
* RESULTS:
** Major vascular events occurred in 24.5% of patients receiving 80 mg [[simvastatin]] versus 25.7% of those receiving 20 mg.
** An average of 0.35 mmol/L greater reduction in LDL-C was observed in the group receiving 80 mg simvastatin compared to those receiving 20 mg.
** Overall 6% reduction in major vascular events was observed in the 80 mg group compared with the 20 mg group.
** [[Myopathy]] occurred in 0.9% patients taking 80 mg simvastatin compared with 0.03% patients in the 20 mg simvastatin group.
* CONCLUSION: The SEARCH study failed to find a benefit with more intensive therapy as a significant number of patients in the 20 mg simvastatin group took an additional statin off protocol as more intensive LDL-C goals were promulgated.
 
===BIP Trial<ref name="pmid10880410">{{cite journal |author= |title=Secondary prevention by raising HDL cholesterol and reducing triglycerides in patients with coronary artery disease: the Bezafibrate Infarction Prevention (BIP) study |journal=[[Circulation]] |volume=102 |issue=1 |pages=21–7 |year=2000 |month=July |pmid=10880410 |doi= |url=}}</ref>===
* This double blinded clinical trial studied the effects of bezafibrate on incidence of cardiovascular events.
* Bezafibrate raised the [[HDL]] levels and decreased the [[triglyceride]] levels in patients with a previous [[myocardial infarction]] or [[stable angina]]. An overall reduction in the risk of cardiovascular events was noted.
 
===CARE Trial<ref name="pmid8801446">{{cite journal |author=Sacks FM, Pfeffer MA, Moye LA, ''et al.'' |title=The effect of pravastatin on coronary events after myocardial infarction in patients with average cholesterol levels. Cholesterol and Recurrent Events Trial investigators |journal=[[The New England Journal of Medicine]] |volume=335 |issue=14 |pages=1001–9 |year=1996 |month=October |pmid=8801446 |doi=10.1056/NEJM199610033351401 |url=}}</ref><ref name="pmid7572695">{{cite journal |author=Pfeffer MA, Sacks FM, Moyé LA, ''et al.'' |title=Cholesterol and Recurrent Events: a secondary prevention trial for normolipidemic patients. CARE Investigators |journal=[[The American Journal of Cardiology]] |volume=76 |issue=9 |pages=98C–106C |year=1995 |month=September |pmid=7572695 |doi= |url=}}</ref>===
* OBJECTIVE: To assess if [[pravastatin]] would reduce the sum of fatal [[coronary artery disease]] ([[CAD]]) and nonfatal myocardial infarction (MI) in patients who had a previous MI and a total cholesterol value < 240 mg/dl.
* METHOD: Cholesterol and Recurrent Events trial was a double blinded, randomized study wherein 4159 patients with a history of a myocardial infarction in the previous two years who had a total cholesterol value < 240 mg/dl were enrolled and treated with either 40 mg pravastatin or a [[placebo]].
* RESULTS and CONCLUSION: The following results were obtained after a median follow-up time of 5 years:
** Reduced combined end point of coronary death and nonfatal [[MI]] (10.2 versus 13.2 percent)
** Reduced need for revascularization with [[CABG]] or [[PTCA]] (14.1 versus 18.8 percent)
** Reduced frequency of stroke (2.6 versus 3.8 percent) and of [[stroke]] plus [[transient ischemic attack]]s (4.4 versus 6.0 percent)
 
===Heart Protection Study<ref name="pmid12114036">{{cite journal |author= |title=MRC/BHF Heart Protection Study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomised placebo-controlled trial |journal=[[Lancet]] |volume=360 |issue=9326 |pages=7–22 |year=2002 |month=July |pmid=12114036 |doi=10.1016/S0140-6736(02)09327-3 |url=}}</ref>===
* OBJECTIVE: To study the effect of [[simvastatin]] therapy that lowers [[LDL]] levels in reducing cardiovascular disease risk.
* METHODS: 20,536 patients with history of [[coronary artery disease]], [[peripheral arterial disease]] or [[diabetes]], were randomly allocated to receive either [[simvastatin]] (40 mg daily) or a placebo. These patients were followed up over a period of 5 years for occurrence of any fatal or non- fatal events, along with incidence of cancer and other causes of major mortality.
* RESULTS: The results of this study are tabulated as follows:
** All cause mortality significantly reduced in the [[simvastatin]] group compared to the placebo group. A highly significant proportional reduction in the coronary death rate, marginally significant reduction in other vascular deaths and a non-significant reduction in non-vascular deaths was noted in the simvastatin group.
** A highly significant reduction in first event rate for non-fatal/fatal myocardial infarction or coronary death, non-fatal/fatal [[stroke]], and for coronary/non-coronary revascularization was noted in the simvastatin group compared to the placebo group.
** This reduction in first event rate was not significant in the first year, whereas found to be highly significant in subsequent years during each separate year.
** The annual excess risk of [[myopathy]] with [[simvastatin]] 40 mg daily was about 0.01 %.
* CONCLUSION: Long term treatment with simvastatin in addition to the existing treatment protocols safely gives an additional benefit to a wide range of high risk patients by reducing mortality.
 
===MEGA Trial<ref name="pmid17011942">{{cite journal |author=Nakamura H, Arakawa K, Itakura H, ''et al.'' |title=Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA Study): a prospective randomised controlled trial |journal=[[Lancet]] |volume=368 |issue=9542 |pages=1155–63 |year=2006 |month=September |pmid=17011942 |doi=10.1016/S0140-6736(06)69472-5 |url=}}</ref><ref name="pmid19246826">{{cite journal |author=Nakamura H |title=[Primary prevention trial by lowering hyperlipidemia on the cardiovascular disease (MEGA Study)] |language=Japanese |journal=[[Nihon Ronen Igakkai Zasshi. Japanese Journal of Geriatrics]] |volume=46 |issue=1 |pages=18–21 |year=2009 |month=January |pmid=19246826 |doi= |url=}}</ref>===
* OBJECTIVE: To assess whether evidence for treatment  of [[hypercholesterolemia]] with [[statin]]s derived from western populations can be extrapolated to the Japanese population.
* METHOD: Primary prevention of cardiovascular disease with pravastatin in Japan (MEGA Study) was a prospective, randomized, open-labelled, blinded study which enrolled 8214 Japanese men and postmenopausal women aged 40 to 70 years and with a serum total cholesterol concentration of 220 to 270 mg/dL. All the patients were randomly assigned to receive either diet therapy alone or diet therapy plus [[pravastatin]] 10 to 20 mg daily and followed-up for a mean period of 5.3 years.
* RESULTS: The following results were obtained at the end of follow-up period:
** Mean total cholesterol was reduced by 2.1% and 11.5% in the patients treated with diet alone and diet plus pravastatin respectively.
** Similarly mean LDL-C reduced by 3.2% and 18.0%.
** Significantly lower [[CAD]] in patients treated with diet plus pravastatin than in those treated with diet alone.
* CONCLUSION: Treatment with a low dose of pravastatin reduces the risk of CAD in Japan by much the same amount as higher doses have shown in Europe and the USA.
 
===MIRACL Study<ref name="pmid11277825">{{cite journal |author=Schwartz GG, Olsson AG, Ezekowitz MD, ''et al.'' |title=Effects of atorvastatin on early recurrent ischemic events in acute coronary syndromes: the MIRACL study: a randomized controlled trial |journal=[[JAMA : the Journal of the American Medical Association]] |volume=285 |issue=13 |pages=1711–8 |year=2001 |month=April |pmid=11277825 |doi= |url=}}</ref><ref name="pmid9514453">{{cite journal |author=Schwartz GG, Oliver MF, Ezekowitz MD, ''et al.'' |title=Rationale and design of the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study that evaluates atorvastatin in unstable angina pectoris and in non-Q-wave acute myocardial infarction |journal=[[The American Journal of Cardiology]] |volume=81 |issue=5 |pages=578–81 |year=1998 |month=March |pmid=9514453 |doi= |url=}}</ref>===
* OBJECTIVE: To assess whether early initiation of treatment with a statin can reduce the occurrence of these early events.
* METHOD: The Myocardial Ischemia Reduction with Acute Cholesterol Lowering (MIRACL) trial was a randomized, double-blinded trial wherein 3086 adults (18 years and above) with [[unstable angina]] or non-Q-wave MI were randomly assigned to receive treatment with [[atorvastatin]] (80 mg/day) or placebo between 24 and 96 hours after hospital admission and followed-up through 16 weeks. Primary predefined end point event was defined as time to death, nonfatal acute MI, [[cardiac arrest]] with [[resuscitation]], or recurrent symptomatic myocardial ischemia with objective evidence and requiring emergency re-hospitalization.
* RESULTS:
** Primary end point occurred in 14.8% in patients treated with atorvastatin compared with 17.4% in the placebo group.
** No significant differences in risk of [[death]], nonfatal myocardial infarction, or cardiac arrest between the two groups.
** Atorvastatin group had a lower risk of symptomatic ischemia with objective evidence and requiring emergency re-hospitalization.
* CONCLUSION: After an acute coronary event early treatment with 80 mg/day atorvastatin reduces recurrent ischemic events in the first 16 weeks, mostly recurrent symptomatic [[ischemia]] requiring re-hospitalization.
 
===PROVE IT-TIMI 22 Trial<ref name="pmid15007110">{{cite journal |author=Cannon CP, Braunwald E, McCabe CH, ''et al.'' |title=Intensive versus moderate lipid lowering with statins after acute coronary syndromes |journal=[[The New England Journal of Medicine]] |volume=350 |issue=15 |pages=1495–504 |year=2004 |month=April |pmid=15007110 |doi=10.1056/NEJMoa040583 |url=}}</ref><ref name="pmid16356805">{{cite journal |author=Rouleau J |title=Improved outcome after acute coronary syndromes with an intensive versus standard lipid-lowering regimen: results from the Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) trial |journal=[[The American Journal of Medicine]] |volume=118 Suppl 12A |issue= |pages=28–35 |year=2005 |month=December |pmid=16356805 |doi=10.1016/j.amjmed.2005.09.014 |url=}}</ref><ref name="pmid17884359">{{cite journal |author=Murphy SA, Cannon CP, Wiviott SD, ''et al.'' |title=Effect of intensive lipid-lowering therapy on mortality after acute coronary syndrome (a patient-level analysis of the Aggrastat to Zocor and Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 trials) |journal=[[The American Journal of Cardiology]] |volume=100 |issue=7 |pages=1047–51 |year=2007 |month=October |pmid=17884359 |doi=10.1016/j.amjcard.2007.04.053 |url=}}</ref><ref name="pmid16226162">{{cite journal |author=Ray KK, Cannon CP, McCabe CH, ''et al.'' |title=Early and late benefits of high-dose atorvastatin in patients with acute coronary syndromes: results from the PROVE IT-TIMI 22 trial |journal=[[Journal of the American College of Cardiology]] |volume=46 |issue=8 |pages=1405–10 |year=2005 |month=October |pmid=16226162 |doi=10.1016/j.jacc.2005.03.077 |url=}}</ref><ref name="pmid18772061">{{cite journal |author=Giraldez RR, Giugliano RP, Mohanavelu S, ''et al.'' |title=Baseline low-density lipoprotein cholesterol is an important predictor of the benefit of intensive lipid-lowering therapy: a PROVE IT-TIMI 22 (Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis In Myocardial Infarction 22) analysis |journal=[[Journal of the American College of Cardiology]] |volume=52 |issue=11 |pages=914–20 |year=2008 |month=September |pmid=18772061 |doi=10.1016/j.jacc.2008.05.046 |url=}}</ref>===
* OBJECTIVE: To determine whether intensive LDL-C lowering with [[atorvastatin]] 80 mg/day was more efficacious than standard LDL-C lowering with [[pravastatin]] 40 mg/day in reducing the incidence of cardiovascular events in patients hospitalized with acute coronary syndrome (ACS) within the preceding 10 days.
* METHOD: Pravastatin or Atorvastatin Evaluation and Infection Therapy-Thrombolysis in Myocardial Infarction 22 (PROVE IT-TIMI 22) trial was a randomized comparative study where in 4162 patients who had been hospitalized for an acute coronary syndrome within the preceding 10 days were enrolled and randomly assigned to treatment with either 40 mg a day pravastatin or 80 mg a day atorvastatin. The primary end point was a composite of death from any cause, myocardial infarction, documented unstable angina requiring re-hospitalization, revascularization (performed at least 30 days after randomization), and [[stroke]].
* RESULTS:
** High-dose atorvastatin group achieved a mean LDL-C level of 62 mg per deciliter compared to 95 mg per deciliter in the standard-dose pravastatin  group.
** The composite end point at 30 days occurred in 3.0% of patients receiving atorvastatin 80 mg versus 4.2% of patients receiving pravastatin 40 mg.
* CONCLUSION: Among patients who have recently had an [[acute coronary syndrome]], an intensive lipid-lowering statin regimen provides greater protection against death or major cardiovascular events than does a standard regimen. These findings indicate that such patients benefit from early and continued lowering of LDL-C to levels substantially below current target levels.
 
===FLORIDA Trial<ref name="pmid12473255">{{cite journal |author=Liem AH, van Boven AJ, Veeger NJ, ''et al.'' |title=Effect of fluvastatin on ischaemia following acute myocardial infarction: a randomized trial |journal=[[European Heart Journal]] |volume=23 |issue=24 |pages=1931–7 |year=2002 |month=December |pmid=12473255 |doi= |url=}}</ref>===
* OBJECTIVE: To assess the effect of fluvastatin on residual [[ischemia]] after acute [[myocardial infarction]].
* METHOD: FLuvastatin On Risk Diminishment after Acute myocardial infarction (FLORIDA) trial was a randomized, placebo-controlled, double-blinded, parallel study that enrolled 540 patients with an acute myocardial infarction and serum cholesterol <251 mg/dL.  The trial used ambulatory electrocardiographic (AECG) monitoring to measure ischemia over 48-h at baseline, after 6 weeks and at 12 months. All the patients were randomized to treatment with either [[fluvastatin]] or [[placebo]].
* RESULTS: The following were the results of the trial:
** At 12 months, the serum [[total cholesterol]] (TC) level was reduced by 13% and LDL-C by 21% in the fluvastatin treatment group compared to a 9% rise in the placebo group.
** AECG monitoring at baseline showed ischemia in 11% of the patients. After 6 weeks, 32/48 (67%), and 12 months 35/46 (76%) of the patients with ischemia on the baseline AECG, no longer showed signs of ischemia.
* CONCLUSION: As compared to placebo, fluvastatin treatment did not affect ischemia on AECG, nor the occurrence of any major clinical events.
 
===Phase Z of A-Z Trial<ref name="pmid15337732">{{cite journal |author=de Lemos JA, Blazing MA, Wiviott SD, ''et al.'' |title=Early intensive vs a delayed conservative simvastatin strategy in patients with acute coronary syndromes: phase Z of the A to Z trial |journal=[[JAMA : the Journal of the American Medical Association]] |volume=292 |issue=11 |pages=1307–16 |year=2004 |month=September |pmid=15337732 |doi=10.1001/jama.292.11.1307 |url=}}</ref><ref name="pmid11479456">{{cite journal |author=Blazing MA, De Lemos JA, Dyke CK, Califf RM, Bilheimer D, Braunwald E |title=The A-to-Z Trial: Methods and rationale for a single trial investigating combined use of low-molecular-weight heparin with the glycoprotein IIb/IIIa inhibitor tirofiban and defining the efficacy of early aggressive simvastatin therapy |journal=[[American Heart Journal]] |volume=142 |issue=2 |pages=211–7 |year=2001 |month=August |pmid=11479456 |doi=10.1067/mhj.2001.116959 |url=}}</ref>===
* OBJECTIVE: To compare early initiation of an intensive [[statin]] regimen with delayed initiation of a less intensive regimen in patients with [[ACS]].
* METHOD: The Z phase of A-Z trial was a multicentered, randomized, double blinded trial which enrolled 4497 patients with acute coronary syndrome who had an initial total cholesterol level ≤250 mg/dL. All the patients were randomized to treatment with either 40 mg/d of [[simvastatin]] for 1 month followed by 80 mg/d thereafter or placebo for 4 months followed by 20 mg/d of simvastatin. All the patients were followed-up for 6 months to 24 months. Primary endpoint was a composite of cardiovascular death, nonfatal [[myocardial infarction]], readmission for ACS, and [[stroke]].
* RESULTS:
** In the less intense treatment group, median LDL-C level achieved while taking [[placebo]] was 122 mg/dL at 1 month and was 77 mg/dL at 8 months while taking 20 mg/d of simvastatin. Corresponding values in the simvastatin only group were 68 mg/dL at 1 month while taking 40 mg/d of simvastatin and 63 mg/dL at 8 months while taking 80 mg/d of simvastatin.
** Primary endpoint was reached in 16.7% in the placebo plus simvastatin group compared with 14.4% in the simvastatin only group.
** Cardiovascular death occurred in 5.4% and 4.1% of the patients in the 2 groups but no differences were observed in other individual components of the primary end point.
* CONCLUSION: The pre-specified end point was not achieved by the trial. However the early initiation of an aggressive simvastatin regimen, in patients with ACS, resulted in a favorable trend toward reduction of major cardiovascular events.
 
===AFREGS Trial<ref name="pmid15657157">{{cite journal |author=Whitney EJ, Krasuski RA, Personius BE, ''et al.'' |title=A randomized trial of a strategy for increasing high-density lipoprotein cholesterol levels: effects on progression of coronary heart disease and clinical events |journal=[[Annals of Internal Medicine]] |volume=142 |issue=2 |pages=95–104 |year=2005 |month=January |pmid=15657157 |doi= |url=}}</ref>===
* OBJECTIVE: To study the angiographic and clinical effects of increasing HDL levels with pharmacologic treatment.
* METHOD: The Air Force Regression Study (AFREGS) was a randomized, double- blinded, placebo controlled trial with 143 patients younger than 76 years of age with low [[HDL]] levels and angiographically evident [[coronary artery disease]]. These patients were randomly allocated to the [[gemfibrozil]], [[niacin]], [[cholestyramine]]and corresponding placebo, with aggressive dietary and lifestyle intervention at baseline. They were then followed up for a period of 30 months for clinical events which includes hospitalization for [[angina]], [[myocardial infarction]], [[transient ischemic attack]] and [[stroke]], [[death]] and other cardiovascular procedures.
* RESULTS:
** The pharmacologically treated group had a 20% decrease in total cholesterol, 36% increase in HDL cholesterol, 26% decrease in [[LDL]] cholesterol and a 50% reduction in triglyceride levels compared to the placebo group.
** Focal coronary stenosis showed an increase of 1.4% in the placebo and a decrease of 0.8% in the drug group.
** 26% of patients in the [[placebo]] group reached a composite cardiovascular event end point whereas the same was seen in 13% of patients in the drug group.
* CONCLUSION: Pharmacologic regimen aimed at raising HDL cholesterol levels improved the [[cholesterol]] levels, retards progressing of [[stenosis]] and prevent cardiovascular events in some who exercise regularly and are on a low-fat diet.
 
===SPARCL Study<ref name="pmid16899775">{{cite journal |author=Amarenco P, Bogousslavsky J, Callahan A, ''et al.'' |title=High-dose atorvastatin after stroke or transient ischemic attack |journal=[[The New England Journal of Medicine]] |volume=355 |issue=6 |pages=549–59 |year=2006 |month=August |pmid=16899775 |doi=10.1056/NEJMoa061894 |url=}}</ref>===
* OBJECTIVE: To study the effects of [[statins]] on [[incidence]] of recurrent stroke after a recent episode of [[stroke]] or [[transient ischemic attack]]
* METHOD: Stroke Prevention by Aggressive Reduction in Cholesterol Levels (SPARCL) was a double blinded study with subjects who had at least one episode of [[stroke]] in the last one to six months and [[LDL]] levels of 100 to 190 mg/dl with no history of [[coronary artery disease]]. These patients were randomly assorted to receive either 80 mg of [[atorvastatin]] daily or placebo. The primary end point for the study was first fatal or non-fatal [[stroke]].
* RESULTS:
** During the mean follow up period of 4.9 years, 11.2% of patients from the [[atorvastatin]] group and 13.1% of patients from the placebo experienced fatal/ non-fatal stroke, with a 5 year absolute risk reduction of 2.2%.
** The 5 year [[absolute risk reduction]] in major cardiovascular events was 3.5%.
** The overall mortality rates were similar in both the groups.
* CONCLUSION: [[Atorvastatin]] (80 mg daily) reduced the [[incidence]] of recurrent [[stroke]] and cardiovascular events in patients with a recent episode of stroke or [[transient ischemic attack]]s. However, the incidence of hemorrhagic stroke increased in the [[atorvastatin]] group.
 
===AVERT Trial<ref name="pmid10395630">{{cite journal |author=Pitt B, Waters D, Brown WV, ''et al.'' |title=Aggressive lipid-lowering therapy compared with angioplasty in stable coronary artery disease. Atorvastatin versus Revascularization Treatment Investigators |journal=[[The New England Journal of Medicine]] |volume=341 |issue=2 |pages=70–6 |year=1999 |month=July |pmid=10395630 |doi=10.1056/NEJM199907083410202 |url=}}</ref><ref name="pmid10653925">{{cite journal |author=Waters DD |title=Medical therapy versus revascularization: the atorvastatin versus revascularization treatment AVERT trial |journal=[[The Canadian Journal of Cardiology]] |volume=16 Suppl A |issue= |pages=11A–3A |year=2000 |month=January |pmid=10653925 |doi= |url=}}</ref>===
* OBJECTIVE: To compare the outcome of aggressive lipid lowering to that of [[angioplasty]] in stable coronary artery disease patients, relatively normal [[left ventricular]] function, asymptomatic or mild-to-moderate [[angina]], and a serum level of LDL-C of at least 115 mg/dL who were referred for percutaneous [[revascularization]].
* METHOD: Atorvastatin versus Revascularization Treatment (AVERT) trial was a randomized comparative study that enrolled 341 patients with stable CAD. All the patients were randomly assigned to treatment with either [[atorvastatin]] 80 mg per day or percutaneous revascularization procedure (angioplasty) followed by usual care. The follow-up period was 18 months.
* RESULTS: At the end of follow-up period atorvastatin was associated with 36% lower incidence of ischemic events compared to angioplasty. Also, patients who received atorvastatin had a significantly longer time to the first ischemic event.
* CONCLUSION: Aggressive lipid lowering therapy with atorvastatin is at least as effective as angioplasty in reducing the incidence of ischemic events in low-risk patients with stable [[CAD]].
 
===CORONA Trial<ref name="pmid17984166">{{cite journal |author=Kjekshus J, Apetrei E, Barrios V, ''et al.'' |title=Rosuvastatin in older patients with systolic heart failure |journal=[[The New England Journal of Medicine]] |volume=357 |issue=22 |pages=2248–61 |year=2007 |month=November |pmid=17984166 |doi=10.1056/NEJMoa0706201 |url=}}</ref><ref name="pmid20152247">{{cite journal |author=van der Harst P, Slart RH, Tio RA, ''et al.'' |title=Effects of rosuvastatin on coronary flow reserve and metabolic mismatch in patients with heart failure (from the CORONA Study) |journal=[[The American Journal of Cardiology]] |volume=105 |issue=4 |pages=517–21 |year=2010 |month=February |pmid=20152247 |doi=10.1016/j.amjcard.2009.10.021 |url=}}</ref><ref name="pmid20023047">{{cite journal |author=Lorgelly PK, Briggs AH, Wedel H, ''et al.'' |title=An economic evaluation of rosuvastatin treatment in systolic heart failure: evidence from the CORONA trial |journal=[[European Journal of Heart Failure]] |volume=12 |issue=1 |pages=66–74 |year=2010 |month=January |pmid=20023047 |pmc=2796144 |doi=10.1093/eurjhf/hfp172 |url=}}</ref><ref name="pmid19917888">{{cite journal |author=McMurray JJ, Kjekshus J, Gullestad L, ''et al.'' |title=Effects of statin therapy according to plasma high-sensitivity C-reactive protein concentration in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA): a retrospective analysis |journal=[[Circulation]] |volume=120 |issue=22 |pages=2188–96 |year=2009 |month=December |pmid=19917888 |doi=10.1161/CIRCULATIONAHA.109.849117 |url=}}</ref>===
* OBJECTIVE: To study the effects of [[rosuvastatin]] 10 mg daily in patients with [[congestive heart failure]].
* METHOD: Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA) was a double-blinded, randomized, placebo controlled trial wherein 5011 patients with [[congestive heart failure]] [[NYHA]] Class II, III or IV ischemic, systolic heart failure were enrolled and randomly assigned to treatment with either 10 mg rosuvastatin daily or placebo. The primary outcome was death from cardiovascular causes, non-fatal MI or non-fatal [[stroke]].
* RESULTS and CONCLUSION: Compared to placebo, [[rosuvastatin]] reduced serum [[LDL]] levels and raised [[HDL]] and [[triglyceride]] levels. However, there was no significant reduction in mortality rates from cardiovascular causes, coronary events and all-cause mortality.
 
===Trials on Investigational Therapies===
===ERASE Trial<ref name="pmid17387133">{{cite journal |author=Tardif JC, Grégoire J, L'Allier PL, ''et al.'' |title=Effects of reconstituted high-density lipoprotein infusions on coronary atherosclerosis: a randomized controlled trial |journal=[[JAMA : the Journal of the American Medical Association]] |volume=297|issue=15 |pages=1675–82 |year=2007 |month=April |pmid=17387133 |doi=10.1001/jama.297.15.jpc70004 |url=}}</ref>===
* OBJECTIVE: To study the effects of reconstituted HDL on atheromatous [[plaque]] volume.
* METHOD: Effect of rHDL on Atherosclerosis - Safety and Efficacy (ERASE)  was a randomized, placebo-controlled trial conducted in 17 centers across Canada. An [[intravascular ultrasound]] was performed at baseline and at 2 to 3 weeks after the last infusion of rHDL to assess plaque burden.
* RESULTS: The group with higher doses of reconstituted HDL (CSL-111) was eliminated from the study because of mild [[liver function test]] abnormalities. The results of the study are briefed below:
** Percentage change in plaque volume: -3.4% with CSL-111 and -1.6% with placebo (P= 0.48 between the groups, P< 0.001 vs baseline for CSL-111)
** Nominal change in plaque volume: -5.3% with CSL-111 and -2.3% with placebo (P= 0.39 between the groups, P< 0.001 vs baseline for CSL-111)
** Mean changes in plaque characterization on IVUS: −0.0097 for CSL-111 and 0.0128 with placebo (P = .01)
** Mean changes in coronary score on [[quantitative coronary angiography]]: −0.039 mm for CSL-111 and −0.071 mm with placebo (P= 0.03)
* CONCLUSION: Short term infusions of reconstituted HDL (CSL-111) resulted in:
** No significant reductions in percentage plaque volume compared to placebo.
** Statistically significant improvement in mean changes in plaque characterization on IVUS and coronary score on quantitative [[coronary angiography]], compared to [[placebo]].
 
===Infusion of Apo A-1 Milano<ref name="pmid14600188">{{cite journal |author=Nissen SE, Tsunoda T, Tuzcu EM, ''et al.'' |title=Effect of recombinant ApoA-I Milano on coronary atherosclerosis in patients with acute coronary syndromes: a randomized controlled trial |journal=[[JAMA : the Journal of the American Medical Association]] |volume=290 |issue=17 |pages=2292–300 |year=2003 |month=November |pmid=14600188 |doi=10.1001/jama.290.17.2292 |url=}}</ref>===
* OBJECTIVE: To study the effects of Apo A-1 Milano on arterial plaque burden.
* METHOD: Apo A-1 was infused in cholesterol fed rabbits and showed a decreased intimal thickness and macrophage content after balloon injury in [[femoral artery|femoral]] and iliac arteries. Based on these results, another pilot trial was designed using recombinant Apo A-1 Milano phospholipid complex (ETC-216) in 57 patients within two weeks of the onset of [[acute coronary syndrome]]. Subjects were randomly assigned to treatment with either ETC 216 infusion at 15 mg/kg or 45 mg/kg or to placebo. [[IVUS]] was performed at baseline and repeated at the completion of the study.
* RESULTS: Treatment with ETC-216 (in both doses) resulted in a significant decrease in mean percentage of coronary artery volume occupied by atheroma as well as the total atheroma volume. Whereas the placebo group did not show any significant change.
* CONCLUSION: Although Apo A-1 Milano infusions resulted in a decrease in plaque burden, further study is required to assess efficacy, safety and cost-effectiveness.
 
===CETP Inhibitors===
====Torcetrapib====
* Clinical research on [[torcetrapib]] stopped because of increased incidence of cardiovascular events as an adverse effect of the drug<ref name="pmid17984165">{{cite journal |author=Barter PJ, Caulfield M, Eriksson M, ''et al.'' |title=Effects of torcetrapib in patients at high risk for coronary events |journal=[[The New England Journal of Medicine]] |volume=357 |issue=21 |pages=2109–22 |year=2007 |month=November |pmid=17984165 |doi=10.1056/NEJMoa0706628 |url=}}</ref>.
* [[Torcetrapib]] side-effects include a significant increase in systolic blood pressure ([[hypertension]]) and a significant reduction in [[serum potassium]] ([[hypokalemia]]) levels.
 
====Anacetrapib====
* Various clinical trials<ref name="pmid19781408">{{cite journal |author=Cannon CP, Dansky HM, Davidson M, ''et al.'' |title=Design of the DEFINE trial: determining the EFficacy and tolerability of CETP INhibition with AnacEtrapib |journal=[[American Heart Journal]] |volume=158 |issue=4 |pages=513–519.e3 |year=2009 |month=October |pmid=19781408 |doi=10.1016/j.ahj.2009.07.028 |url=}}</ref><ref name="pmid18068514">{{cite journal |author=Krishna R, Anderson MS, Bergman AJ, ''et al.'' |title=Effect of the cholesteryl ester transfer protein inhibitor, anacetrapib, on lipoproteins in patients with dyslipidaemia and on 24-h ambulatory blood pressure in healthy individuals: two double-blind, randomised placebo-controlled phase I studies |journal=[[Lancet]] |volume=370 |issue=9603 |pages=1907–14 |year=2007 |month=December |pmid=18068514 |doi=10.1016/S0140-6736(07)61813-3 |url=}}</ref> showed that [[anacetrapib]] significantly lowers [[LDL]] cholesterol and raises [[HDL]] levels without any increase in [[systolic blood pressure]].
 
====Dalcetrapib====
* Research studies on [[dalcetrapib]] were stopped due to lack of clinically and statistically meaningful efficacy of the drug on interim analysis<ref name="pmid22345126">{{cite journal |author=Lüscher TF, Taddei S, Kaski JC, ''et al.'' |title=Vascular effects and safety of dalcetrapib in patients with or at risk of coronary heart disease: the dal-VESSEL randomized clinical trial |journal=[[European Heart Journal]] |volume=33 |issue=7 |pages=857–65 |year=2012 |month=April |pmid=22345126 |pmc=3345558 |doi=10.1093/eurheartj/ehs019 |url=}}</ref>.
* The Dal-Outcomes study<ref name="pmid23126252">{{cite journal |author=Schwartz GG, Olsson AG, Abt M, ''et al.'' |title=Effects of dalcetrapib in patients with a recent acute coronary syndrome |journal=[[The New England Journal of Medicine]] |volume=367 |issue=22 |pages=2089–99 |year=2012 |month=November |pmid=23126252 |doi=10.1056/NEJMoa1206797 |url=}}</ref> assessed dalcetrapib at various dose ranges. This study showed a significant rise in [[HDL]] levels, but there was no significant difference between the drug and the placebo group.
 
====Evacetrapib====
* [[Evacetrapib]] has been proved to be a promising CETP inhibitor as it does not show any elevations in [[blood pressure]] or [[aldosterone]]/[[cortisol]] levels<ref name="pmid22362199">{{cite journal |author=Nicholls SJ |title=Evacetrapib |journal=[[Current Cardiology Reports]] |volume=14 |issue=3 |pages=245–50 |year=2012 |month=June |pmid=22362199 |doi=10.1007/s11886-012-0252-3 |url=}}</ref><ref name="pmid21957197">{{cite journal |author=Cao G, Beyer TP, Zhang Y, ''et al.'' |title=Evacetrapib is a novel, potent, and selective inhibitor of cholesteryl ester transfer protein that elevates HDL cholesterol without inducing aldosterone or increasing blood pressure |journal=[[Journal of Lipid Research]] |volume=52 |issue=12 |pages=2169–76 |year=2011 |month=December |pmid=21957197 |pmc=3220285 |doi=10.1194/jlr.M018069 |url=}}</ref>.
* It increases [[HDL]]-C and decreases [[LDL]]-C levels in a dose dependent manner<ref name="pmid22089718">{{cite journal |author=Nicholls SJ, Brewer HB, Kastelein JJ, ''et al.'' |title=Effects of the CETP inhibitor evacetrapib administered as monotherapy or in combination with statins on HDL and LDL cholesterol: a randomized controlled trial |journal=[[JAMA : the Journal of the American Medical Association]] |volume=306 |issue=19 |pages=2099–109 |year=2011 |month=November |pmid=22089718 |doi=10.1001/jama.2011.1649 |url=}}</ref>.
 
==References==
{{Reflist|2}}


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Latest revision as of 14:21, 21 October 2013

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Hilda Mahmoudi M.D., M.P.H.[2]

Reconstituted HDL Infusion

Name of the Trial Official Title Status ClinicalTrials.gov Identifier Drug name Trial phase
Effect of CER-001 on Atherosclerosis in Acute Coronary Syndrome (ACS) Patients - Efficacy and Safety: The CHI SQUARE Trial CHI SQUARE: Can HDL Infusions Significantly Quicken Atherosclerosis Regression? A Phase II, Multi-Center, Double-Blind, Ascending Dose, Placebo-Controlled, Dose-Finding Trial of CER-001 or Placebo in Subjects With Acute Coronary Syndrome Ongoing NCT01201837 CER-001 (an ApoA-I-based HDL mimetic) 2
Effect of CER-001 on Plaque Volume in Homozygous Familial Hypercholesterolemia (HoFH) Subjects (MODE) Modifying Orphan Disease Evaluation (MODE) Study: A Multicenter, Open-label Study of the Effects of CER-001 on Plaque Volume in Subjects With Homozygous Familial Hypercholesterolemia (HoFH) Ongoing NCT01412034 CER-001 (an ApoA-I-based HDL mimetic) 2
Exploratory Study of Plaque Regression (EXPRESS) EXPLORATORY STUDY OF PLAQUE REGRESSION:A Phase II Single Center Open-Label Exploratory Trial of the Effect of CER 001 in Subjects With Familial Hypercholesterolemia Completed NCT01515241 CER-001 (an ApoA-I-based HDL mimetic) 2
A Multiple Ascending Dose Study of CSL112 in Healthy Volunteers An Adaptive, Phase I, Randomised, Placebo-controlled, Sponsor-unblinded, Multiple Ascending Dose Study to Investigate the Safety, Tolerability and Pharmacokinetics of Intravenous CSL112 in Healthy Volunteers Completed NCT01281774 CSL112 (reconstituted HDL) 1
Safety, Tolerability and Pharmacokinetics of CSL112 in Healthy Volunteers An Adaptive, Phase I, Single-Centre, Randomised, Double-blind, Placebo-controlled Single Ascending Dose Study to Investigate the Safety, Tolerability and Pharmacokinetics, of Intravenous CSL112 in Healthy Volunteers Completed NCT01129661 CSL112 (reconstituted HDL) 1
A Single Ascending Dose Study Examining the Safety and Pharmacokinetic Profile of Reconstituted High Density Lipoprotein (CSL112) Administered to Patients A Phase 2a, Multi-center, Randomized, Double-blind, Placebo-controlled, Single Ascending Dose Study to Investigate the Safety, Tolerability and Pharmacokinetics of a Single Intravenous Infusion of CSL112in Patients With Stable Atherothrombotic Disease Completed NCT01499420 CSL112 (reconstituted HDL) 2
Effect of rHDL on Atherosclerosis - Safety and Efficacy:THE ERASE TRIAL Regression of Coronary Atherosclerotic Lesions After rHDL Infusions in Acute Coronary Syndrome Patients as Assessed by Intravascular Ultrasound Completed NCT00225719 rHDL 2
Improving Metabolism With HDL Cholesterol A Novel Mechanism Mediating Anti-atherosclerotic and Metabolic Actions of HDL Cholesterol Completed NCT00395148 rHDL
Effect of Recombinant ApoA-I Milano on Coronary Atherosclerosis in Patients With Acute Coronary Syndromes Apo A-1 Milano, ETC 216, MDCO 216 3

CETP Inhibitors

Name of the Trial Official Title Status ClinicalTrials.gov Identifier Drug name Trial phase
A Study of Evacetrapib in High-Risk Vascular Disease (ACCELERATE) Assessment of Clinical Effects of Cholesteryl Ester Transfer Protein Inhibition With Evacetrapib in Patients at a High-Risk for Vascular Outcomes Ongoing NCT01687998 Evacetrapib 3
A Study of Evacetrapib (LY2484595) in Participants With Kidney Impairment and in Healthy Participants Pharmacokinetics of Evacetrapib (LY2484595) Following Administration to Subjects With Impaired Renal Function Ongoing NCT01825889 Evacetrapib 3
A Study of Evacetrapib in Healthy Participants Effect of Gemfibrozil on the Pharmacokinetics of Evacetrapib (LY2484595) in Healthy Subjects Completed NCT01736254 Evacetrapib 1
A Study of Evacetrapib (LY2484595) in Participants With Hepatic (Liver) Impairment Pharmacokinetics of Evacetrapib (LY2484595) in Subjects With Hepatic Impairment Ongoing NCT01836185 Evacetrapib 1
A Study of Evacetrapib (LY2484595) in Healthy Participants A Bioequivalence Study in Healthy Subjects Administered Evacetrapib Tablets of Varying Tablet Solid Fractions Ongoing NCT01903434 Evacetrapib 1
Study of Food on Evacetrapib (LY2484595) in Healthy Participants Effect of Food on the Pharmacokinetics of Evacetrapib (LY2484595) in Healthy Subjects Completed NCT01810432 Evacetrapib 1
A Study of Evacetrapib and Rifampin in Healthy Participants Effect of Rifampin on the Pharmacokinetics of Evacetrapib in Healthy Subjects Ongoing NCT01908582 Evacetrapib 1
A Study of LY2484595 on Pharmacokinetics in Healthy Subjects A Phase 1 Study to Evaluate the Safety and Tolerability of LY2484595 SDSD-PG Tablets and the Effect of CYP3A Inhibition by Ketoconazole on the Pharmacokinetics of LY2484595 in Healthy Subjects Completed NCT01448824 Evacetrapib 1
A Study of Evacetrapib (LY2484595) and Warfarin in Healthy Participants Effect of Evacetrapib on the Pharmacokinetics and Pharmacodynamics of Warfarin in Healthy Subjects Completed NCT01825876 Evacetrapib 1
A Study of LY2484595 in Patients With High LDL-C or Low HDL-C A Phase 2 Efficacy and Safety Study of LY2484595 Alone and in Combination With Atorvastatin, Simvastatin, and Rosuvastatin in Patients With Hypercholesterolemia or Low HDL-C Completed NCT01105975 Evacetrapib 2
A Study of Evacetrapib in Healthy Female Participants Effects of Evacetrapib (LY2484595) on the Pharmacokinetics of an Oral Contraceptive in Healthy Female Subjects Completed NCT01746732 Evacetrapib 1
A Study of Evacetrapib and Digoxin in Healthy Participants Effect of Evacetrapib on the Pharmacokinetics of Digoxin in Healthy Subjects Ongoing NCT01897493 Evacetrapib 1
A Study of LY2484595 in Healthy Subjects Single Dose LY2484595 Tablet Formulations to Determine the Impact of Dose Level, Food, and Ethnicity on the Pharmacokinetics in Healthy Subjects Completed NCT01450098 Evacetrapib 1
A Study of LY2484595 in Japanese Subjects A Phase 2 Dose Response Study of LY2484595 in Japanese Subjects Completed NCT01375075 Evacetrapib 2
A Study of LY2484595 on the Electrical Activity of the Heart A Placebo- and Positive-Controlled Study of the Effect of LY2484595 on QT Interval in Healthy Subjects Completed NCT01537887 Evacetrapib 1
A Study of LY2484595 in Patients With High LDL-C or Low HDL-C A Phase 2 Efficacy and Safety Study of LY2484595 Alone and in Combination With Atorvastatin, Simvastatin, and Rosuvastatin in Patients With Hypercholesterolemia or Low HDL-C Completed NCT01105975 Evacetrapib 2
A Study of LY2484595 on Pharmacokinetics in Healthy Subjects A Phase 1 Study to Evaluate the Safety and Tolerability of LY2484595 SDSD-PG Tablets and the Effect of CYP3A Inhibition by Ketoconazole on the Pharmacokinetics of LY2484595 in Healthy Subjects Completed NCT01448824 Evacetrapib 1
A Study of RO4607381 in Stable Coronary Heart Disease Patients With Recent Acute Coronary Syndrome( dal-OUTCOMES Trial) A Randomized, Double-blind, Placebo-controlled Study Assessing the Effect of RO4607381 on Cardiovascular Mortality and Morbidity in Clinically Stable Patients With a Recent Acute Coronary Syndrome Completed NCT00658515 Dalcetrapib 3
A Formulation Screening Study of Dalcetrapib and Atorvastatin in Healthy Volunteers A Single-center, Randomized, Open-label, Four Treatments, Four Periods, Four Sequence, Four-way Crossover Study to Explore the Pharmacokinetic Performance of Dalcetrapib and Atorvastatin Fixed Dose Combination Prototype Formulations in Healthy Volunteers Completed NCT01363999 Dalcetrapib 1
A Study of Dalcetrapib in Patients With Stable Coronary Heart Disease, With Coronary Heart Disease Risk Equivalents or at Elevated Risk for Cardiovascular Disease A Phase 3b, Multi-Center, Double-Blind, Placebo-Controlled, Parallel Group, Study to Evaluate the Effect of Dalcetrapib 600 mg on Cardiovascular (CV) Events in Adult Patients With Stable Coronary Heart Disease (CHD), CHD Risk Equivalents or at Elevated Risk for Cardiovascular Disease (CVD) Completed NCT01516541 Dalcetrapib 3
A Study of the Effect of Dalcetrapib on Artherosclerotic Disease in Patients With Coronary Artery Disease A Multi-Center, Double-blind, Randomized, Placebo Controlled, Parallel Group Study of the Effect of Dalcetrapib on Atherosclerotic Disease Progression As Measured by Coronary Intravascular Ultrasound, Carotid B-Mode Ultrasound and Coronary Angiography Completed NCT01059682 Dalcetrapib 3
A Study of Dalcetrapib in Patients Hospitalized For An Acute Coronary Syndrome (Dal-ACUTE) A Phase III, Double-blind, Randomized, Placebo-controlled, Multi-center Study Evaluating the Efficacy and Safety of Dalcetrapib on Lipids, Lipoproteins, Apolipoproteins and Markers of CV Risk in Patients Hospitalized for an Acute Coronary Syndrome (ACS) When Treatment is Initiated Within 1 Week After an ACS (Dal-ACUTE) Completed NCT01323153 Dalcetrapib 3
A Study of the Metabolic Profile of Dalcetrapib in Healthy Volunteers An Open Label, Single Centre Study to Investigate the Metabolic Profile of Dalcetrapib After a Single Oral Dose in Healthy Male Subjects Completed NCT01476267 Dalcetrapib 1
A Study of RO4607381 in Stable Coronary Heart Disease Patients With Recent Acute Coronary Syndrome A Phase II, Double-Blind, Randomized, Placebo-controlled, Parallel Group Study, Evaluating the Efficacy and Safety of RO4607381 Over a 24-week Period in Patients With CHD or a CHD Risk Equivalent Completed NCT00353522 Dalcetrapib 2
A Study Assessing the Effect of RO4607381 on Vascular Function in Patients With Coronary Heart Disease (CHD) or CHD-Risk Equivalent Patient Dal-VESSEL Trial A Randomized, Placebo-controlled Study of the Safety, Tolerability and Effect on Endothelial Function, as Measured by Flow Mediated Dilatation, of RO4607381 in Patients With Coronary Heart Disease (CHD) or CHD Risk Equivalents Completed NCT00655538 Dalcetrapib 2
A Long Term Extension of Study NC19453 Evaluating Safety and Efficacy of RO4607381 A Phase II, Placebo-Controlled, Double-Blind Extension Study of Study NC19453 Assessing Long-term Safety and Efficacy of RO4607381 Completed NCT00400439 Dalcetrapib 2
A Study of the Effect of RO4607381 on Atherosclerotic Plaque in Patients With Coronary Heart Disease (Dal-PLAQUE Trial) A Randomized, Placebo-controlled Study of the Effect of RO4607381 on Progression or Regression of Atherosclerotic Plaque in Patients With Coronary Heart Disease (CHD) Including Patients With Other CHD Risk Factors Completed NCT00655473 Dalcetrapib 2
Efficacy and Safety Study of JTT-705 in Combination With Pravastatin 40 mg in Patients With Type II Hyperlipidemia A 4-Week, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study Evaluating the Efficacy and Safety of JTT-705 (300 mg or 600 mg) Versus Placebo in Combination With Pravastatin 40 mg in Patients With Type II Hyperlipidemia completed NCT00688896 Dalcetrapib 2
Efficacy and Safety of JTT-705 300, 600 And 900mg in Comparison With Placebo in Patients With Type II Hyperlipidaemia A 4-Weeks Treatment, Randomised, Double-Blind, Parallel-Group Study Evaluating The Efficacy and Safety of JTT-705 300 to 900mg in Comparison With Placebo in Patients With Type II Hyperlipidaemia Completed NCT00686010 Dalcetrapib 2
Safety and Efficacy Study of JTT-705 in Combination With Atorvastatin 20 mg in Patients With Low High-Density Lipoprotein (HDL) Levels A 4-Week, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study Evaluating the Safety and Efficacy of JTT-705 600 mg Versus Placebo Administered Once Daily in Combination With Atorvastatin 20 mg in Patients With Low HDL Levels Completed NCT00689442 Dalcetrapib 2
Safety and Efficacy Study of JTT-705 in Combination With Simvastatin 40 mg in Patients With Low High-Density Lipoprotein (HDL) Levels A 4-Week, Randomized, Double-Blind, Placebo-Controlled, Parallel Group Study Evaluating the Safety and Efficacy of JTT-705 600 mg Versus Placebo Administered Once Daily in Combination With Simvastatin 40 mg in Patients With Low HDL Levels completed NCT00688558 Dalcetrapib 2
Study to Assess the Tolerability and Efficacy of Anacetrapib in Patients With Coronary Heart Disease (CHD) or CHD Risk-Equivalent Disease (MK-0859-019 AM6; EXT1 [AM2]) (DEFINE Trial) A 76-Week, Worldwide, Multicenter, Double-Blind, Randomized, Placebo-Controlled Study to Assess the Tolerability and Efficacy of Anacetrapib When Added to Ongoing Therapy With a Statin in Patients With Coronary Heart Disease (CHD) or CHD Risk-Equivalent Disease Ongoing NCT00685776 Anacetrapib 3
A Study of the Safety and Efficacy of Anacetrapib (MK-0859) When Added to Ongoing Statin Therapy (MK-0859-021 AM1) A 24-Week, Worldwide, Multicenter, Double-Blind, Randomized, Parallel, Placebo-Controlled Study to Assess the Efficacy and Tolerability of Anacetrapib When Added to Ongoing Statin Therapy With or Without Other Lipid Modifying Medication(s) in Patients With Hypercholesterolemia or Low HDL-C Ongoing NCT01717300 Anacetrapib 3
A Study of the Safety and Efficacy of Anacetrapib (MK-0859) When Added to Ongoing Statin Therapy in Japanese Participants With Dyslipidemia (MK-0859-051 AM1) A Multicenter, 24-Week, Double-Blind, Randomized, Placebo-Controlled, Phase III Study With 28-Week Open Labeled Extension Period to Assess the Efficacy and Safety of MK-0859 When Added to Ongoing Statin Therapy With or Without Other Lipid Modifying Medication(s) in Japanese Patients With Dyslipidemia Ongoing NCT01760460 Anacetrapib 3
Pharmacokinetics of Anacetrapib (MK0859) in Patients With Hepatic Insufficiency (MK-0859-039) A Single Dose Study to Investigate the Pharmacokinetics of MK0859 in Patients With Hepatic Insufficiency Completed NCT01114490 Anacetrapib 1
A Study of the Safety and Efficacy of Anacetrapib (MK-0859) When Added to Ongoing Statin Therapy in Japanese Participants With Heterozygous Familial Hypercholesterolemia (MK-0859-050) A 12-Week, Multicenter, Double-Blind, Randomized, Parallel, Placebo-Controlled Study to Assess the Efficacy and Safety of MK-0859 When Added to Ongoing Statin Therapy With or Without Other Lipid Modifying Therapies in Japanese Patients With Heterozygous Familial Hypercholesterolemia Ongoing NCT01824238 Anacetrapib 3
Pharmacokinetics of Anacetrapib (MK0859) in Subjects With Impaired Renal Function (MK-0859-038) A Single-Dose Study to Investigate the Pharmacokinetics of MK0859 in Subjects With Impaired Renal Function Completed NCT01122667 Anacetrapib 1
REVEAL: Randomized EValuation of the Effects of Anacetrapib Through Lipid-modification REVEAL: Randomized EValuation of the Effects of Anacetrapib Through Lipid-modification. A Large-scale, Randomized Placebo-controlled Trial of the Clinical Effects of Anacetrapib Among People With Established Vascular Disease Ongoing NCT01252953 Anacetrapib 3
Efficacy and Tolerability of Anacetrapib Added to Ongoing Lipid-Lowering Therapy in Adult Participants With Homozygous Familial Hypercholesterolemia (HoFH) (MK-0859-042 AM2) A Worldwide, Multicenter, Double-Blind, Randomized, Placebo-Controlled, 12-Week Study to Assess the Efficacy and Tolerability of Anacetrapib When Added to Ongoing Lipid-Lowering Therapy in Adult Patients With Homozygous Familial Hypercholesterolemia (HoFH) Ongoing NCT01841684 Anacetrapib 3
A Study of the Safety and Efficacy of Anacetrapib (MK-0859) Among Participants With Hypercholesterolemia When Added to Ongoing Statin Therapy (MK-0859-022 AM4) A 24-Week, Worldwide, Multicenter, Double-Blind, Randomized, Parallel, Placebo- Controlled Study to Assess the Efficacy and Tolerability of Anacetrapib When Added to Ongoing Statin Therapy With or Without Other Lipid Modifying Medication(s) in Patients With Hypercholesterolemia or Low HDL-C Ongoing NCT01860729 Anacetrapib 3
A Study of the Safety and Efficacy of Anacetrapib (MK-0859) Among Participants With Hypercholesterolemia When Added to Ongoing Statin Therapy (MK-0859-022 AM4) A 24-Week, Worldwide, Multicenter, Double-Blind, Randomized, Parallel, Placebo- Controlled Study to Assess the Efficacy and Tolerability of Anacetrapib When Added to Ongoing Statin Therapy With or Without Other Lipid Modifying Medication(s) in Patients With Hypercholesterolemia or Low HDL-C Ongoing NCT01860729 Anacetrapib 3
Study to Assess the Tolerability and Efficacy of Anacetrapib Co-administered With Statin in Participants With Heterozygous Familial Hypercholesterolemia (MK-0859-020 AM1) (REALIZE) A 1-Year, Worldwide, Multicenter, Double-Blind, Randomized, Parallel, Placebo- Controlled Study to Assess the Efficacy and Tolerability of Anacetrapib When Added to Ongoing Statin Therapy With or Without Other Lipid Modifying Medication(s) in Patients With Heterozygous Familial Hypercholesterolemia Ongoing NCT01524289 Anacetrapib 3
A Study of Safety and Efficacy of MK0859 (Anacetrapib) in Japanese Patients With Dyslipidemia (0859-029)(COMPLETED) A Phase IIb, Multicenter, Randomized, Placebo-Controlled, Double-Blind, Dose-Ranging Study to Assess the Efficacy and Safety of MK0859 in Japanese Patients With Dyslipidemia Completed NCT00977288 Anacetrapib 2
The Effect of MK0859 on Lipoprotein Metabolism in Patients With Dyslipidemia (0859-026 AM3) A Multiple Dose Study to Investigate the Effect of MK0859 on Lipoprotein Metabolism When Added to Ongoing Statin Therapy in Dyslipidemic Patients Completed NCT00990808 Anacetrapib 1
MK0859 Dose-Ranging Study (0859-003 MK0859 Dose-Ranging Study Terminated NCT00325455 Anacetrapib 2
A Study of MK0859 in Patients With Primary Hypercholesterolemia or Mixed Hyperlipidemia Completed NCT00565292 Anacetrapib 1
A Study Examining Torcetrapib/Atorvastatin And Atorvastatin Effects On Clinical CV Events In Patients With Heart Disease (ILLUMINATE) Phase 3 Multi Center, Double Blind, Randomized, Parallel Group Evaluation Of The Fixed Combination Torcetrapib/Atorvastatin, Administered Orally, Once Daily (Qd), Compared With Atorvastatin Alone, On The Occurrence Of Major Cardiovascular Events In Subjects With Coronary Heart Disease Or Risk Equivalents Terminated NCT00134264 Torcetrapib 3
Assess HDL-C Increase And Non-HDL Lowering Effect Of Torcetrapib/Atorvastatin Vs. Fenofibrate Phase 3 Multi-Center, Double-Blind, Randomized, Parallel Group, Forced Titration Study Of The Efficacy, Safety, And Tolerability Of Torcetrapib/Atorvastatin Compared To Fenofibrate In Subjects With Fredrickson Type IIB Dyslipidemia (Mixed Hyperlipidemia Completed NCT00139061 Torcetrapib 3
Study To Evaluate The Effect Of Torcetrapib/Atorvastatin In Patients With Genetic High Cholesterol Disorder Phase 3 Multi-Center, Open Label, Forced Titration Study To Evaluate The Efficacy, Safety, And Tolerability Of Torcetrapib/Atorvastatin Combination Administered Orally, Once Daily (Qd) In Patients With Homozygous Familial Hypercholesterolaemia Completed NCT00134511 Torcetrapib 3
Study To Evaluate The Safety And Efficacy Of Torcetrapib/Atorvastatin In Subjects With Familial Hypercholerolemia Phase 3, Multi-Center, Double-Blind, Randomized, Parallel Group, Study of the Efficacy, Safety, and Tolerability of Fixed Combination Torcetrapib (CP-529,414) / Atorvastatin Administered Orally, Once Daily (QD) for Six Months, Compared With Maximally Tolerated Atorvastatin Therapy Alone, in Subjects With Heterozygous Familial Hypercholesterolemia Completed NCT00134485 Torcetrapib 3
Study To Evaluate The Effect Of Torcetrapib/Atorvastatin In Subjects With A Genetic Cholesterol Disorder Phase 3, Multi-Center, Double-Blind, Randomized, Crossover Study Of The Efficacy, Safety, And Tolerability Of Fixed Combination Torcetrapib (Cp-529,414)/Atorvastatin, Compared With Atorvastatin Therapy Alone, And Fenofibrate Alone, In Subjects With Fredrickson Type III Hyperlipoproteinemia (Familial Dysbetalipoproteinemia) Terminated NCT00145431 Torcetrapib 3
A Study Comparing The Efficacy & Safety Of Torcetrapib/Atorvastatin And Atorvastatin In Subjects With High Triglycerides Phase 3, Multi-Site, Double-Blind, Randomized, Forced Titration, Parallel Group Evaluation Of The Efficacy, Safety, And Tolerability Of Fixed Combination Torcetrapib (CP 529,414)/Atorvastatin Administered Orally, Once Daily (Qd) For Eighteen Weeks, Compared With Atorvastatin Alone, In Subjects With Fredrickson Type IV Hypertriglyceridemia Completed NCT00134498 Torcetrapib 3
A Clinical Trial Comparing Torcetrapib/Atorvastatin To Simvastatin In Subjects With High Cholesterol A Phase 3, Open-Label, Multisite, Randomized, Parallel Group Study of the Efficacy and Safety of Fixed Combination Torcetrapib/Atorvastatin Administered Once Daily (QD) Compared to Simvastatin for 6 Weeks in Subjects With Hypercholesterolemia (A5091030) Completed NCT00267254 Torcetrapib 3
A Study of Torcetrapib/Atorvastatin vs Atorvastatin Alone or Placebo in Patients With High Cholesterol A Phase 3, Double Blind, Placebo-Controlled, Randomized, Parallel Group, Multicenter Study of the Efficacy, Safety and Tolerability of Fixed Combination Torcetrapib/Atorvastatin Administered Orally Once Daily for 6 Months, Compared to Atorvastatin Alone or Placebo in Subjects With Mixed Dyslipidemia (Fredrickson Types IIa and IIb). Completed NCT00138762 Torcetrapib 3
A Clinical Trial Comparing Torcetrapib/Atorvastatin To Simvastatin In Subjects With High Cholesterol (A5091031). A Phase 3, Open-Label, Multisite, Randomized, Parallel Group Study of the Efficacy and Safety of Fixed Combination Torcetrapib/Atorvastatin Administered Once Daily (QD) Compared to Simvastatin for 6 Weeks in Subjects With Hypercholesterolemia (A5091031) Terminated NCT00267280 Torcetrapib 3
A Clinical Trial Comparing Torcetrapib/Atorvastatin to Ezetimibe/Simvastatin In Subjects With A Cholesterol Disorder. Phase 3, Open-Label, Multi-Center, Double-Blind, Randomized, Parallel Group Study Efficacy and Safety of Fixed Combination Torcetrapib/Atorvastatin, Administered Once Daily (QD) Compared to Fixed Combination Ezetimibe/Simvastatin for 6 Weeks in Subjects With Dyslipidemia Terminated NCT00267267 Torcetrapib 3
Carotid B-mode Ultrasound Study to Compare Anti-Atherosclerotic Effect of Torcetrapib/Atorvastatin to Atorvastatin. (RADIANCE 2) Phase 3 Multi-Center, Double-Blind, Randomized, Parallel Group, Carotid B-mode Ultrasound Evaluation of the Anti-Atherosclerotic Efficacy, Safety, and Tolerability of Fixed Combination CP-529,414/Atorvastatin, Administered Orally, Once Daily (QD) for 24 Months, Compared With Atorvastatin Alone, in Subjects With Mixed Hyperlipidemia Terminated NCT00134238 Torcetrapib 3
A Coronary IVUS Study to Compare Torcetrapib/Atorvastatin to Atorvastatin Alone in Subjects With Coronary Heart Disease (ILLUSTRATE) Phase 3, Multi-Center, Double-Blind, Randomized, Parallel Group, Coronary Artery Intravascular Ultrasound Evaluation of the Anti-Atherosclerotic Efficacy, Safety, and Tolerability of Fixed Combination CP-529,414/Atorvastatin, Administered Orally, Once Daily (QD) for 24 Months, Compared With Atorvastatin Alone, in Subjects With Angiographically Documented Coronary Heart Disease. Completed NCT00134173 Torcetrapib 3
Safety FollowUp Study Of Cardiovascular Events In Subjects Who Participated In Selected Torcetrapib/Atorvastatin Studies An Observational Safety Follow Up Trial Of The Occurrence Of Major Cardiovascular Events And All Cause Mortality In Subjects Who Participated In Selected Torcetrapib/Atorvastatin Clinical Trials. Terminated NCT00452842 Torcetrapib Observational
Lipitor Trial To Study The Effect Of Torcetrpib/Atorvastatin To Atorvastatin Alone. A Phase 3, Double-Blind, Randomized, Multisite Trial Of The Efficacy, Safety, And Tolerability Of The Fixed Combination Torcetrapib/Atorvastatin Administered Orally, Once Daily For 12 Months, Compared To Atorvastatin Alone, Titrated Based On NCEP ATP-III LDL-C Goals In Subjects With Fredrickson Types IIa And IIb Dyslipidemias Completed NCT00137462 Torcetrapib 3
Carotid B-Mode Ultrasound Study to Compare Anti-Atherosclerotic Effect of Torcetrpib/Atorvastatin to Atorvastatin Alone. (RADIANCE 1) Phase 3 Multi-Center, Double-Blind, Randomized, Parallel Group, Carotid B-Mode Ultrasound Evaluation of the Anti-Atherosclerotic Efficacy, Safety and Tolerability of Fixed Combination CP-529,414/Atorvastatin, Administered Orally, Once Daily (QD) for 24 Months, Compared With Maximally Tolerated Atorvastatin Therapy Alone, in Subjects With Heterozygous Familial Hypercholesterolemia. Completed NCT00136981 Torcetrapib 3

Niacin

Name of the Trial Official Title Status ClinicalTrials.gov Identifier Drug name Trial phase
Niacin Plus Statin to Prevent Vascular Events (AIM-HIGH Trial) AIM HIGH: Niacin Plus Statin to Prevent Vascular Events Terminated NCT00120289 Niacin Phase 3
Carotid Plaque Characteristics by MRI in AIM-HIGH (Carotid MRI Substudy) (AIM-HIGH Trial) Carotid Plaque Characteristics by MRI in AIM-HIGH Ongoing NCT01178320 Simvastatin +Niacin Observational
Plaque Inflammation and Dysfunctional HDL Cholesterol in Participants Receiving Niacin and Statins in the AIM-HIGH Study (The HDL Proteomics Study) (AIM-HIGH Trial) Plaque Inflammation and Dysfunctional HDL in AIM-HIGH Completed NCT00880178 Simvastatin +Niacin Observational
ARBITER 2 Trial
ARBITER 3 Trial
Comparative Study of the Effect of Ezetimibe Versus Extended-Release Niacin on Atherosclerosis (ARBITER 6-HALTS Trial) ARBITER 6: ARterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 6 - HDL and LDL Treatment Strategies in Atherosclerosis (HALTS) Terminated NCT00397657 Ezetimibe, Niacin Phase 4
CLAS Trial
HDL-Atherosclerosis Treatment Study (HATS) HDL-Atherosclerosis Treatment Study (HATS) Completed NCT00000553 Simvastatin, Niacin, Antioxidants Phase 3
Oxford Niaspan Study Oxford Niaspan Study: Effects of Niaspan on Atherosclerosis and Endothelial Function Cardiovascular Magnetic Resonance Evaluation of the Effects of Niaspan on Regression of Atherosclerosis and Restoration of Endothelial Function Unknown NCT00232531 Interventional (study phase not provided)

Fibrate

VA-HIT Trial
BECAIT Trial
BIP Trial

Statin

ASTEROID Trial
SATURN Trial
4S Trial
CORONA Trial

Multiple Lipid Lowering Drugs

HARP Study
AFREGS Trial



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