View source for Chronic stable angina treatment angiotensin converting enzyme inhibitors (ACEI) and renin angiotensin aldosterone system blockers (RAAS blockers)

__NOTOC__
{{Chronic stable angina}}

'''Editor-In-Chief:''' [[C. Michael Gibson, M.S., M.D.]] [mailto:charlesmichaelgibson@gmail.com] Phone:617-632-7753; '''Associate Editor(s)-In-Chief:''' [[Lakshmi Gopalakrishnan|Lakshmi Gopalakrishnan, M.B.B.S.]]

==Overview==
Patients diagnosed with [[syndrome X]] and [[hypertension]] may have microvascular angina characterized by a reduced coronary vasodilator reserve and increased sympathetic drive. [[ACE inhibitors|ACE inhibition]] in such patients may attenuate sympathetic coronary vasoconstriction, normalize [[Chronic stable angina myocardial perfusion scintigraphy|thallium perfusion defects]] and reduce [[Chronic stable angina exercise electrocardiography|exercise-induced ischemia]] with subsequent increased myocardial oxygen supply.<ref name="pmid8113548">Kaski JC, Rosano G, Gavrielides S, Chen L (1994) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=8113548 Effects of angiotensin-converting enzyme inhibition on exercise-induced angina and ST segment depression in patients with microvascular angina.] ''J Am Coll Cardiol'' 23 (3):652-7. PMID: [http://pubmed.gov/8113548 8113548]</ref><ref name="pmid11216965">van den Heuvel AF, Dunselman PH, Kingma T, Verhorst P, Boomsma F, van Gilst WH et al. (2001) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11216965 Reduction of exercise-induced myocardial ischemia during add-on treatment with the angiotensin-converting enzyme inhibitor enalapril in patients with normal left ventricular function and optimal beta blockade.] ''J Am Coll Cardiol'' 37 (2):470-4. PMID: [http://pubmed.gov/11216965 11216965]</ref> Based on the recent [[ACC AHA guidelines classification scheme|AHA]] and [[European society of cardiology|ESC]] guidelines, the recommended goal [[blood pressure]] in patients with [[CAD|atherosclerotic coronary vascular disease]] is less than 130/80 mm Hg.<ref name="pmid17998462">Fraker TD, Fihn SD, Gibbons RJ, Abrams J, Chatterjee K, Daley J et al. (2007)[http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17998462 2007 chronic angina focused update of the ACC/AHA 2002 Guidelines for the management of patients with chronic stable angina: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines Writing Group to develop the focused update of the 2002 Guidelines for the management of patients with chronic stable angina.] ''Circulation'' 116 (23):2762-72.[http://content.onlinejacc.org/cgi/reprint/50/23/2264.pdf] PMID: [http://pubmed.gov/17998462 17998462]</ref><ref name="pmid16735367">{{cite journal| author=Fox K, Garcia MA, Ardissino D, Buszman P, Camici PG, Crea F et al.| title=Guidelines on the management of stable angina pectoris: executive summary: The Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology. | journal=Eur Heart J | year= 2006 | volume= 27 | issue= 11 | pages= 1341-81 | pmid=16735367 | doi=10.1093/eurheartj/ehl001 | pmc= |url=url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16735367 [http://www.escardio.org/guidelines-surveys/esc-guidelines/GuidelinesDocuments/guidelines-angina-FT.pdf]}} </ref><ref name="pmid17502569">Rosendorff C, Black HR, Cannon CP, Gersh BJ, Gore J, Izzo JL et al. (2007) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17502569 Treatment of hypertension in the prevention and management of ischemic heart disease: a scientific statement from the American Heart Association Council for High Blood Pressure Research and the Councils on Clinical Cardiology and Epidemiology and Prevention.] ''Circulation'' 115 (21):2761-88. [http://dx.doi.org/10.1161/CIRCULATIONAHA.107.183885 DOI:10.1161/CIRCULATIONAHA.107.183885] PMID: [http://pubmed.gov/17502569 17502569]</ref>

==ACEI/RAAS Blockers==
===Mechanisms of Benefit===
*[[ACEIs|ACE inhibition]] in patients with [[syndrome X]] and [[hypertension]] may attenuate sympathetic coronary vasoconstriction and reduce [[Chronic stable angina exercise electrocardiography|exercise-induced ischemia]] with subsequent increased myocardial oxygen supply.<ref name="pmid8113548">Kaski JC, Rosano G, Gavrielides S, Chen L (1994) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=8113548 Effects of angiotensin-converting enzyme inhibition on exercise-induced angina and ST segment depression in patients with microvascular angina.] ''J Am Coll Cardiol'' 23 (3):652-7. PMID: [http://pubmed.gov/8113548 8113548]</ref><ref name="pmid11216965">van den Heuvel AF, Dunselman PH, Kingma T, Verhorst P, Boomsma F, van Gilst WH et al. (2001) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11216965 Reduction of exercise-induced myocardial ischemia during add-on treatment with the angiotensin-converting enzyme inhibitor enalapril in patients with normal left ventricular function and optimal beta blockade.] ''J Am Coll Cardiol'' 37 (2):470-4. PMID: [http://pubmed.gov/11216965 11216965]</ref>

*In one meta-analysis, researchers found that high blood pressure was strongly and directly related to overall mortality. Therefore, lowering blood pressure provides a greater benefit in the reduction of cardiovascular mortality and improves prognosis.<ref name="pmid12493255">Lewington S, Clarke R, Qizilbash N, Peto R, Collins R, Prospective Studies Collaboration (2002) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12493255 Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies.] ''Lancet'' 360 (9349):1903-13. PMID: [http://pubmed.gov/12493255 12493255]</ref> However, blood pressure lowering effects were found to be similar among [[angiotensin converting enzyme inhibitors]] ([[ACEIs]]), [[angiotensin receptor blockers]] ([[ARB|ARBs]]) and [[Chronic stable angina treatment calcium channel blockers|calcium channel blockers]].<ref name="pmid14615107">Turnbull F, Blood Pressure Lowering Treatment Trialists' Collaboration (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=14615107 Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials.] ''Lancet'' 362 (9395):1527-35. PMID: [http://pubmed.gov/14615107 14615107]</ref><ref name="pmid12777939">Staessen JA, Wang JG, Thijs L (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12777939 Cardiovascular prevention and blood pressure reduction: a quantitative overview updated until 1 March 2003.] ''J Hypertens'' 21 (6):1055-76. [http://dx.doi.org/10.1097/01.hjh.0000059044.65882.db DOI:10.1097/01.hjh.0000059044.65882.db] PMID: [http://pubmed.gov/12777939 12777939]</ref>

*The relative risk reduction for composite primary end-points with [[ACEIs|ACE inhibition]] was significant in the ''HOPE'' (26%; 95% CI 13–36) and ''EUROPA'' trials (14%; 95% CI 23 to 28); however, the ''PEACE'' study (5%; 95% CI 219 to 24) found no significant risk reduction. These differences in cardiovascular outcomes were attributed to the difference in non-study related therapies such as [[Chronic stable angina treatment beta blockers|beta-blocker]], [[Chronic stable angina treatment calcium channel blockers|CCBs]] or [[Chronic stable angina treatment anti-lipid agents|lipid-lowering agents]] received at baseline.<ref name="pmid11479247">Dagenais GR, Yusuf S, Bourassa MG, Yi Q, Bosch J, Lonn EM et al. (2001) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11479247 Effects of ramipril on coronary events in high-risk persons: results of the Heart Outcomes Prevention Evaluation Study.] ''Circulation'' 104 (5):522-6. PMID: [http://pubmed.gov/11479247 11479247]</ref><ref name="pmid13678872">Fox KM, EURopean trial On reduction of cardiac events with Perindopril in stable coronary Artery disease Investigators (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=13678872 Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study).] ''Lancet'' 362 (9386):782-8. PMID: [http://pubmed.gov/13678872 13678872]</ref><ref name="pmid15531767">Braunwald E, Domanski MJ, Fowler SE, Geller NL, Gersh BJ, Hsia J et al. (2004) [http://www.ncbi.nlm.nih.gov/entrez/eutils/eink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15531767 Angiotensin-converting-enzyme inhibition in stable coronary artery disease.] ''N Engl J Med'' 351 (20):2058-68. [http://dx.doi.org/10.1056/NEJMoa042739 DOI:10.1056/NEJMoa042739] PMID: [http://pubmed.gov/15531767 15531767]</ref>
:*A significant reduction in the incidence of [[heart failure]] was a common benefit observed in all the three trials.
:*In the ''MICROHOPE'' study, a substudy with a different focus that did not involve primary [[blood pressure]]-lowering study, reported similar benefits with [[ACEIs|angiotensin converting enzyme inhibition]] in [[diabetic patients]] as observed in the ''HOPE'' trial. Similar [[Chronic stable angina prognosis|prognosis]] was also observed in the high-risk and intermediate risk groups with the use of [[ramipril]] and [[perindopril]] respectively.<ref name="pmid11276395">Luft FC (2001) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11276395 Recent clinical trial highlights in hypertension.] ''Curr Hypertens Rep'' 3 (2):133-8. PMID: [http://pubmed.gov/11276395 11276395]</ref>

*In [[diabetics]] with [[MI|post-MI]], [[ACEI|ACE inhibition]] may slow the rate of progression of [[Chronic renal failure|proteinuric chronic renal failure]].<ref name="pmid12777938">European Society of Hypertension-European Society of Cardiology Guidelines Committee (2003)[http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12777938 2003 European Society of Hypertension-European Society of Cardiology guidelines for the management of arterial hypertension.] ''J Hypertens'' 21 (6):1011-53.[http://dx.doi.org/10.1097/01.hjh.0000059051.65882.32 DOI:10.1097/01.hjh.0000059051.65882.32]PMID: [http://pubmed.gov/12777938 12777938]</ref><ref name="pmid12502618">American Diabetes Association (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12502618 Standards of medical care for patients with diabetes mellitus.] ''Diabetes Care'' 26 Suppl 1 ():S33-50. PMID: [http://pubmed.gov/1250261812502618]</ref>

===Indications===
*[[ACEIs|ACE inhibition]] has been shown to be effective in the treatment of [[Chronic stable angina definition|stable angina]] only with co-existing [[hypertension]], [[diabetes]], [[heart failure]], [[LV dysfunction|asymptomatic LV dysfunction]], or [[MI|post-MI]]. Efficacy has not been shown otherwise.<ref name="pmid12502618">American Diabetes Association (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12502618 Standards of medical care for patients with diabetes mellitus.] ''Diabetes Care'' 26 Suppl 1 ():S33-50. PMID: [http://pubmed.gov/12502618 12502618]</ref><ref name="pmid10523396">Faggiotto A, Paoletti R (1999) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=10523396 State-of-the-Art lecture. Statins and blockers of the renin-angiotensin system: vascular protection beyond their primary mode of action.] ''Hypertension'' 34 (4 Pt 2):987-96. PMID: [http://pubmed.gov/10523396 10523396]</ref><ref name="pmid7923694">Lonn EM, Yusuf S, Jha P, Montague TJ, Teo KK, Benedict CR et al. (1994) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=7923694 Emerging role of angiotensin-converting enzyme inhibitors in cardiac and vascular protection.] ''Circulation'' 90 (4):2056-69. PMID: [http://pubmed.gov/7923694 7923694]</ref>

*In patients with [[coronary artery disease]] and preserved left ventricular function, [[ACEIs]] may be indicated for secondary preventive therapy.<ref name="pmid13678872">Fox KM, EURopean trial On reduction of cardiac events with Perindopril in stable coronary Artery disease Investigators (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=13678872 Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study).] ''Lancet'' 362 (9386):782-8. PMID: [http://pubmed.gov/13678872 13678872]</ref><ref name="pmid15531767">Braunwald E, Domanski MJ, Fowler SE, Geller NL, Gersh BJ, Hsia J et al. (2004) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15531767 Angiotensin-converting-enzyme inhibition in stable coronary artery disease.] ''N Engl J Med'' 351 (20):2058-68. [http://dx.doi.org/10.1056/NEJMoa042739 DOI:10.1056/NEJMoa042739] PMID: [http://pubmed.gov/15531767 15531767]</ref><ref name="pmid10639539">Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G (2000) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=10639539 Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators.] ''N Engl J Med'' 342 (3):145-53. [http://dx.doi.org/10.1056/NEJM200001203420301 DOI:10.1056/NEJM200001203420301] PMID: [http://pubmed.gov/10639539 10639539]</ref>

*[[ACEIs]] or [[ARB|ARBs]] has shown to prevent the progression of [[renal dysfunction]] and hence are used as the first-line of agents in the management of [[hypertension]] in [[diabetics]] with [[microalbuminuria]].<ref name="pmid12777938">European Society of Hypertension-European Society of Cardiology Guidelines Committee (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12777938 2003 European Society of Hypertension-European Society of Cardiology guidelines for the management of arterial hypertension.] ''J Hypertens'' 21 (6):1011-53. [http://dx.doi.org/10.1097/01.hjh.0000059051.65882.32 DOI:10.1097/01.hjh.0000059051.65882.32] PMID: [http://pubmed.gov/12777938 12777938]</ref><ref name="pmid12502618">American Diabetes Association (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12502618 Standards of medical care for patients with diabetes mellitus.] ''Diabetes Care'' 26 Suppl 1 ():S33-50. PMID: [http://pubmed.gov/12502618 12502618]</ref>

*[[ARB|ARBs]] may be used in patients who are intolerant to [[ACEIs]] and are indicated in [[Chronic stable angina definition|stable angina]] patients with concomitant [[heart failure]], [[hypertension]] or [[diabetes|diabetic renal dysfunction]]. However, [[ARB|ARBs]] may not be indicated in patients with preserved LV function as a secondary preventive therapy.<ref name="pmid13678871">Yusuf S, Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ et al. (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=13678871 Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial.] ''Lancet'' 362 (9386):777-81. [http://dx.doi.org/10.1016/S0140-6736(03)14285-7 DOI:10.1016/S0140-6736(03)14285-7] PMID: [http://pubmed.gov/13678871 13678871]</ref>

===Adverse Effects===
In comparison to other anti-hypertensive drugs, [[ACEIs]] although remain the standard drug of choice for [[hypertension]] and [[heart failure]], it has not been shown to confer overall protection against cardiovascular complications.<ref name="pmid14615107">Turnbull F, Blood Pressure Lowering Treatment Trialists' Collaboration (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=14615107 Effects of different blood-pressure-lowering regimens on major cardiovascular events: results of prospectively-designed overviews of randomised trials.] ''Lancet'' 362 (9395):1527-35. PMID: [http://pubmed.gov/14615107 14615107]</ref><ref name="pmid12777939">Staessen JA, Wang JG, Thijs L (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12777939 Cardiovascular prevention and blood pressure reduction: a quantitative overview updated until 1 March 2003.] ''J Hypertens'' 21 (6):1055-76. [http://dx.doi.org/10.1097/01.hjh.0000059044.65882.db DOI:10.1097/01.hjh.0000059044.65882.db] PMID: [http://pubmed.gov/12777939 12777939]</ref><ref name="pmid12759325">Psaty BM, Lumley T, Furberg CD, Schellenbaum G, Pahor M, Alderman MH et al. (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12759325 Health outcomes associated with various antihypertensive therapies used as first-line agents: a network meta-analysis.] ''JAMA'' 289 (19):2534-44. [http://dx.doi.org/10.1001/jama.289.19.2534 DOI:10.1001/jama.289.19.2534] PMID: [http://pubmed.gov/12759325 12759325]</ref>

===Supportive Trial Data Demonstrating Significant Benefit with the use of ACEIs or ARBs===
*In the ''HOPE'' trial, 9,297 [[Chronic stable angina assessing the pretest probability of coronary artery disease|high-risk]] patients with evidence of vascular disease or [[diabetes]] plus one other cardiovascular risk factor in the absence of [[heart failure]] were randomized to receive either [[ramipril]] (10 mg/day) or placebo. The goal of the trial was to assess the role of [[ACEIs|angiotensin-converting-enzyme inhibitor]] in the management of patients who were at increased risk for cardiovascular events and with [[EF|preserved left ventricular function]]. The primary end-points from cardiovascular causes of mortality (6.1% in the ramipril group vs. 8.1% in the placebo group; relative risk, 0.74; P<0.001), [[MI|non-fatal MI]] (9.9% vs. 12.3%; relative risk, 0.80; P<0.001), [[stroke]] (3.4% vs. 4.9%; relative risk, 0.68; P<0.001) and complications related to [[diabetes]] (6.4% vs. 7.6%; relative risk, 0.84; P=0.03) were significantly reduced in the [[ramipril]] group as observed during a mean follow-up time of 5 years. The 22% relative risk reduction in cardiovascular death, [[myocardial infarction]], or [[stroke]] observed with [[ramipril]] was independent of other therapies such as [[Chronic stable angina treatment aspirin|aspirin]], [[Chronic stable angina treatment beta blockers|beta-blockers]] and [[Chronic stable angina treatment anti-lipid agents|anti-lipid agents]].<ref name="pmid11479247">Dagenais GR, Yusuf S, Bourassa MG, Yi Q, Bosch J, Lonn EM et al. (2001) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11479247 Effects of ramipril on coronary events in high-risk persons: results of the Heart Outcomes Prevention Evaluation Study.] ''Circulation'' 104 (5):522-6. PMID: [http://pubmed.gov/11479247 11479247]</ref><ref name="pmid11909785">Bosch J, Yusuf S, Pogue J, Sleight P, Lonn E, Rangoonwala B et al. (2002) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11909785 Use of ramipril in preventing stroke: double blind randomised trial.] ''BMJ'' 324 (7339):699-702. PMID: [http://pubmed.gov/11909785 11909785]</ref> Thus, the study was prematurely terminated after a 5-year follow-up, as [[ramipril]] was associated with a significant reduction in the mortality, [[MI]] and [[stroke]] in high-risk patients with preserved ejection fraction.<ref name="pmid10639539">Yusuf S, Sleight P, Pogue J, Bosch J, Davies R, Dagenais G (2000) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=10639539 Effects of an angiotensin-converting-enzyme inhibitor, ramipril, on cardiovascular events in high-risk patients. The Heart Outcomes Prevention Evaluation Study Investigators.] ''N Engl J Med'' 342 (3):145-53. [http://dx.doi.org/10.1056/NEJM200001203420301 DOI:10.1056/NEJM200001203420301] PMID: [http://pubmed.gov/10639539 10639539]</ref><ref name="pmid12204499">Lonn E, Roccaforte R, Yi Q, Dagenais G, Sleight P, Bosch J et al. (2002) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12204499 Effect of long-term therapy with ramipril in high-risk women.] ''J Am Coll Cardiol'' 40 (4):693-702. PMID: [http://pubmed.gov/12204499 12204499]</ref><ref name="pmid10675071"> (2000) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=10675071 Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: results of the HOPE study and MICRO-HOPE substudy. Heart Outcomes Prevention Evaluation Study Investigators.] ''Lancet'' 355 (9200):253-9. PMID: [http://pubmed.gov/10675071 10675071]</ref>

:*In a sub-study, that hypothesized the benefits of [[ramipril]] use was not confined to the reduction in blood pressure alone, researchers calculated the blood-pressure-related risk estimates from the placebo group of the ''HOPE'' trial and from earlier studies. The study concluded that the benefits associated with [[ramipril]] were additive in patients with normal or higher than normal [[blood pressure|baseline blood pressure]].<ref name="pmid11784631">Sleight P, Yusuf S, Pogue J, Tsuyuki R, Diaz R, Probstfield J et al. (2001) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11784631 Blood-pressure reduction and cardiovascular risk in HOPE study.] ''Lancet'' 358 (9299):2130-1. [http://dx.doi.org/10.1016/S0140-6736(01)07186-0 DOI:10.1016/S0140-6736(01)07186-0] PMID: [http://pubmed.gov/11784631 11784631]</ref>

:*In another substudy, that assessed the comparative effects of [[ramipril]] on [[blood pressure|ambulatory (ABP)]] and [[blood pressure|office blood pressures (OBP)]], researchers observed that [[ramipril]] did not significantly reduce the [[blood pressure|OBP]] (8/2 mm Hg, P=not significant) or [[blood pressure|ABP]] (6/2 mm Hg, P=not significant) after 1 year. However, the 24-hour ABP was significantly reduced (10/4 mm Hg, P=0.03), as a consequent of a more pronounced blood pressure lowering effect occurring during nighttime (17/8 mm Hg, P<0.001).<ref name="pmid11751742">Svensson P, de Faire U, Sleight P, Yusuf S, Ostergren J (2001) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=11751742 Comparative effects of ramipril on ambulatory and office blood pressures: a HOPE Substudy.] ''Hypertension'' 38 (6):E28-32. PMID: [http://pubmed.gov/11751742 11751742]</ref>

*In the ''EUROPA'' trial, 13,655 patients with previous [[myocardial infarction]] (64%), angiographic evidence of [[coronary artery disease]] (61%), [[revascularization|coronary revascularisation]] (55%), or a [[Chronic stable angina risk assessment in patients with an intermediate or high probability of coronary artery disease|positive stress test]] (5%), were randomized to receive either [[perindopril]] (8 mg/day) or placebo. The goal of the study was to assess the effect of [[ACEI|ACE inhibition]] in the reduction of cardiovascular risk in patients with [[Chronic stable angina definition|stable coronary artery disease]] in the absence of [[heart failure]]. The study designs of both the ''HOPE'' and ''EUROPA'' trials were similar; however, the ''EUROPA'' trial involved patients with lower rates of [[hypertension]], [[diabetes]] and [[peripheral artery disease]] (27% in the ''EUROPA'' trial vs. 47% in the ''HOPE'' trial). Approximately, a 20% relative reduction in the primary endpoint of all cardiovascular causes of mortality including [[MI]] or [[cardiac arrest]] during a mean follow-up of 4.2 years was observed in the [[perindopril]] group (8% vs. 10%, 95% CI 9-29, p=0.0003). Thus, the study concluded that in patients with [[Chronic stable angina definition|stable coronary heart disease]] without apparent [[heart failure]], [[perindopril]] significantly improved outcomes.<ref name="pmid13678872">Fox KM, EURopean trial On reduction of cardiac events with Perindopril in stable coronary Artery disease Investigators (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=13678872 Efficacy of perindopril in reduction of cardiovascular events among patients with stable coronary artery disease: randomised, double-blind, placebo-controlled, multicentre trial (the EUROPA study).] ''Lancet'' 362 (9386):782-8. PMID: [http://pubmed.gov/13678872 13678872]</ref>

:*Data collected from the ''PERSUADE'' substudy further strengthened the benefit of [[perindopril]] in the reduction of major cardiovascular events in [[DM|diabetic]] patients with [[CAD|coronary disease]].<ref name="pmid15860521">Daly CA, Fox KM, Remme WJ, Bertrand ME, Ferrari R, Simoons ML et al. (2005) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15860521 The effect of perindopril on cardiovascular morbidity and mortality in patients with diabetes in the EUROPA study: results from the PERSUADE substudy.] ''Eur Heart J'' 26 (14):1369-78. [http://dx.doi.org/10.1093/eurheartj/ehi225 DOI:10.1093/eurheartj/ehi225] PMID: [http://pubmed.gov/15860521 15860521]</ref>

:*In another substudy, involving 12,056 patients with [[Chronic stable angina definition|stable coronary artery disease]] without [[heart failure]] which assessed the benefit of [[ACEIs|ACE inhibition]] in patients with mild to moderate [[renal insufficiency]], researchers reported similar benefits of [[perindopril]] consistent with the ''EUROPA'' trial. Researchers also stated that the effects of [[ACEIs|ACE inhibition]] were not modified by the presence of mild to moderate [[renal insufficiency]].<ref name="pmid18036453">Brugts JJ, Boersma E, Chonchol M, Deckers JW, Bertrand M, Remme WJ et al. (2007) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=18036453 The cardioprotective effects of the angiotensin-converting enzyme inhibitor perindopril in patients with stable coronary artery disease are not modified by mild to moderate renal insufficiency: insights from the EUROPA trial.] ''J Am Coll Cardiol'' 50 (22):2148-55. [http://dx.doi.org/10.1016/j.jacc.2007.08.029 DOI:10.1016/j.jacc.2007.08.029] PMID: [http://pubmed.gov/18036453 18036453]</ref>

*In the ''CAMELOT'' trial, 1991 patients with angiographically documented [[CAD]] and [[Blood pressure|diastolic blood pressure]] less than 100 mm Hg, were randomized to receive either [[amlodipine]] (10mg), [[enalapril]] (20 mg), or placebo; to compare the effects of [[amlodipine]] or [[enalapril]] vs placebo on cardiovascular events in patients with [[CAD]]. The mean baseline [[blood pressure]] was 129/78 mm Hg and both [[amlodipine]] and [[enalapril]] caused significant reductions in the blood pressure (4.8/2.5 and 4.9/2.4 vs. 0.7/0.6 mmHg; p<0.001 for both vs. placebo). At 1-year follow-up, a 16% significant reduction in the primary end-point of all cardiovascular causes of mortality and incidence of cardiovascular events was observed in the [[amlodipine]] group (hazard ratio 0.69; 95% CI, 0.54-0.88; p=0.003). However, no significant difference was observed with the other two groups: 23.1% in the placebo group and 20.2% in the [[enalapril]] group (hazard ratio 0.85; 95% CI, 0.67-1.07; p=0.16). Thus, the study concluded in patients with [[CAD]] and normal blood pressure, the administration of [[amlodipine]] resulted in reduced cardiovascular events; however, similar smaller and non-significant benefits were observed with [[enalapril]].<ref name="pmid15536108">Nissen SE, Tuzcu EM, Libby P, Thompson PD, Ghali M, Garza D et al. (2004) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15536108 Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure: the CAMELOT study: a randomized controlled trial.] ''JAMA'' 292 (18):2217-25. [http://dx.doi.org/10.1001/jama.292.18.2217 DOI:10.1001/jama.292.18.2217] PMID: [http://pubmed.gov/15536108 15536108]</ref>

:*The ''IVUS'' substudy, involving 274 patients with normal [[blood pressure]] at baseline, reported a significant correlation between the progression of [[atherosclerosis]] and the reduction in blood pressure with the administration of [[amlodipine]].<ref name="pmid15536108">Nissen SE, Tuzcu EM, Libby P, Thompson PD, Ghali M, Garza D et al. (2004) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15536108 Effect of antihypertensive agents on cardiovascular events in patients with coronary disease and normal blood pressure: the CAMELOT study: a randomized controlled trial.] ''JAMA'' 292 (18):2217-25. [http://dx.doi.org/10.1001/jama.292.18.2217 DOI:10.1001/jama.292.18.2217] PMID: [http://pubmed.gov/15536108 15536108]</ref>

:*The ''VALUE'' study, involving 15,245 [[hypertension|hypertensive]] patients with high cardiovascular risk (46% patients had [[CAD]]) who were randomized to receive either [[amlodipine]] or [[valsartan]]. At 4.2 year follow-up, no significant difference in the primary composite endpoint was observed between the two groups. Thus, the study emphasized the importance of prompt [[blood pressure]] control to reduce the incidence of cardiac mortality and morbidity, irrespective of the type of anti-hypertensive agent being used.<ref name="pmid15207952">Julius S, Kjeldsen SE, Weber M, Brunner HR, Ekman S, Hansson L et al. (2004) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15207952 Outcomes in hypertensive patients at high cardiovascular risk treated with regimens based on valsartan or amlodipine: the VALUE randomised trial.] ''Lancet'' 363 (9426):2022-31. [http://dx.doi.org/10.1016/S0140-6736(04)16451-9 DOI:10.1016/S0140-6736(04)16451-9] PMID: [http://pubmed.gov/15207952 15207952]</ref>

*In the ''VALIANT'' trial, 14,703 [[MI|post-MI]] patients with [[heart failure]], reported no significant difference in the prognosis of [[ischemic heart disease]] between the [[valsartan]] and [[captopril]] groups.<ref name="pmid19576338">Califf RM, Lokhnygina Y, Velazquez EJ, McMurray JJ, Leimberger JD, Lewis EF et al. (2009) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=19576338 Usefulness of beta blockers in high-risk patients after myocardial infarction in conjunction with captopril and/or valsartan (from the VALsartan In Acute Myocardial Infarction [VALIANT] trial).] ''Am J Cardiol'' 104 (2):151-7. [http://dx.doi.org/10.1016/j.amjcard.2009.03.020 DOI:10.1016/j.amjcard.2009.03.020] PMID: [http://pubmed.gov/19576338 19576338]</ref>

*A recent 2011 meta-analysis, reviewed 25 randomized controlled trials involving 63,000 patients to evaluate the effect of anti-hypertensive agents such as [[ACEIs]], [[ARB|ARBs]], [[beta-blockers]], [[CCB|calcium channel blockers]] on the secondary prevention of cardiovascular events and all-cause mortality among patients without clinically defined [[hypertension]]. The relative risk ratios in comparison to control group was: 0.85 for composite cardiovascular events, 0.83 for cardiovascular mortality, 0.87 for all-cause mortality, 0.80 for [[MI]], 0.71 for [[CHF]] and 0.77 for [[stroke]], with the corresponding [[Absolute risk reduction|ARR]] per 1000 persons treated was -27.1 (95% CI, -40.3 to -13.9) for composite cardiovascular events, -15.4 (95% CI, -32.5 to 1.7) for cardiovascular mortality, -13.7 (95% CI, -24.6 to -2.8) for all-cause mortality, -13.3 (95% CI, -28.4 to 1.7) for [[MI]], -43.6 (95% CI, -65.2 to -22.0) for [[CHF]] and -7.7 (95% CI, -15.2 to -0.3) for [[stroke]]. Thus, the study concluded that in patients with documented cardiovascular disease without [[hypertension]], there was a significant reduction in the risk of composite cardiovascular events and all-cause mortality associated with anti-hypertensive therapy. Researchers suggested that no specific benefit was achieved with the use of [[ACEIs]] or [[ARBs]] in comparison to other anti-hypertensive agents.<ref name="pmid21364140">Thompson AM, Hu T, Eshelbrenner CL, Reynolds K, He J, Bazzano LA (2011) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=21364140 Antihypertensive treatment and secondary prevention of cardiovascular disease events among persons without hypertension: a meta-analysis.] ''JAMA'' 305 (9):913-22. [http://dx.doi.org/10.1001/jama.2011.250 DOI:10.1001/jama.2011.250] PMID: [http://pubmed.gov/21364140 21364140]</ref>

===Supportive Trial Data Demonstrating No Benefit with the use of ACEIs or ARBs===
*In the ''PEACE'' trial, 8,290 patients with a mean baseline blood pressure 133/78, were randomized to receive either [[trandolapril]] (4mg/day) or placebo. Researchers hypothesized that patients with [[Chronic stable angina definition|stable coronary artery disease]] without [[heart failure]] derive therapeutic benefit from the addition of [[ACEIs|ACE inhibitors]] to conventional therapy. The primary end point from all causes of mortality, [[MI]], [[revascularization|coronary revascularization]] during a median 4.8 year follow-up did not differ between the two groups: 21.9% in the [[trandolapril]] group and 22.5% in the placebo group (p=0.43). Thus, the study concluded that the addition of an [[ACEIs|ACE inhibitor]] provided no further benefit in terms of death from cardiovascular causes, [[myocardial infarction]], or [[revascularization|coronary revascularization]].<ref name="pmid15531767">Braunwald E, Domanski MJ, Fowler SE, Geller NL, Gersh BJ, Hsia J et al. (2004) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=15531767 Angiotensin-converting-enzyme inhibition in stable coronary artery disease.] ''N Engl J Med'' 351 (20):2058-68. [http://dx.doi.org/10.1056/NEJMoa042739 DOI:10.1056/NEJMoa042739] PMID: [http://pubmed.gov/15531767 15531767]</ref>

*In the ''TRACE'' study, a consequent to ''PEACE'' trial which involved 1,749 [[diabetic]] [[MI|post-MI]] patients with [[LV dysfunction]] who were assessed for the efficacy of long-term treatment with the [[ACEIs|angiotensin-converting enzyme inhibitor]], researchers reported a non-significant reduction in [[MI|non-fatal MI]] observed at 26-month follow-up. However, [[trandolapril]] markedly reduced the risk of progression to [[heart failure|severe heart failure]].<ref name="pmid10399995">Gustafsson I, Torp-Pedersen C, Køber L, Gustafsson F, Hildebrandt P (1999) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=10399995 Effect of the angiotensin-converting enzyme inhibitor trandolapril on mortality and morbidity in diabetic patients with left ventricular dysfunction after acute myocardial infarction. Trace Study Group.] ''J Am Coll Cardiol'' 34 (1):83-9. PMID: [http://pubmed.gov/10399995 10399995]</ref>

*In the ''CHARM-preserved'' study, 3023 patients with [[New york heart association functional classification|class II-IV CHF]] and [[EF|LVEF]] greater than 40% at baseline were randomized to receive either [[candesartan]] (32 mg/day) or placebo. Researchers assessed the effect of addition of an [[ARB]] to the current regimen. It was reported that the primary end-point of cardiovascular causes of mortality during a median follow-up of 36.6 months did not differ significantly between the two groups: 22% in the [[candesartan]] group and 24% in the placebo group (p=0.118). Thus, the study reported no significant benefit observed with the use of [[candesartan]] in patients with preserved LV function.<ref name="pmid13678871">Yusuf S, Pfeffer MA, Swedberg K, Granger CB, Held P, McMurray JJ et al. (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=13678871 Effects of candesartan in patients with chronic heart failure and preserved left-ventricular ejection fraction: the CHARM-Preserved Trial.] ''Lancet'' 362 (9386):777-81. [http://dx.doi.org/10.1016/S0140-6736(03)14285-7 DOI:10.1016/S0140-6736(03)14285-7] PMID: [http://pubmed.gov/13678871 13678871]</ref>

==2007 Chronic Angina Focused Update of the ACC/AHA 2002 Guidelines and the 2002 Guideline Update for the Management of Patients With Chronic Stable Angina (DO NOT EDIT) <ref name="pmid17998462">Fraker TD, Fihn SD, Gibbons RJ, Abrams J, Chatterjee K, Daley J et al. (2007)[http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17998462 2007 chronic angina focused update of the ACC/AHA 2002 Guidelines for the management of patients with chronic stable angina: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines Writing Group to develop the focused update of the 2002 Guidelines for the management of patients with chronic stable angina.] ''Circulation'' 116 (23):2762-72.[http://content.onlinejacc.org/cgi/reprint/50/23/2264.pdf] PMID: [http://pubmed.gov/17998462 17998462]</ref><ref name="pmid12515758">Gibbons RJ, Abrams J, Chatterjee K, Daley J, Deedwania PC, Douglas JS et al. (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12515758 ACC/AHA 2002 guideline update for the management of patients with chronic stable angina--summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Chronic Stable Angina).] ''Circulation'' 107 (1):149-58.[http://content.onlinejacc.org/cgi/reprint/41/1/159.pdf] PMID: [http://pubmed.gov/12515758 12515758]</ref>==

===Renin-Angiotensin-Aldosterone Receptor Blockers (DO NOT EDIT)<ref name="pmid17998462">Fraker TD, Fihn SD, Gibbons RJ, Abrams J, Chatterjee K, Daley J et al. (2007)[http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=17998462 2007 chronic angina focused update of the ACC/AHA 2002 Guidelines for the management of patients with chronic stable angina: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines Writing Group to develop the focused update of the 2002 Guidelines for the management of patients with chronic stable angina.] ''Circulation'' 116 (23):2762-72.[http://content.onlinejacc.org/cgi/reprint/50/23/2264.pdf] PMID: [http://pubmed.gov/17998462 17998462]</ref><ref name="pmid12515758">Gibbons RJ, Abrams J, Chatterjee K, Daley J, Deedwania PC, Douglas JS et al. (2003) [http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&retmode=ref&cmd=prlinks&id=12515758 ACC/AHA 2002 guideline update for the management of patients with chronic stable angina--summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Chronic Stable Angina).] ''Circulation'' 107 (1):149-58.[http://content.onlinejacc.org/cgi/reprint/41/1/159.pdf] PMID: [http://pubmed.gov/12515758 12515758]</ref>===

{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LightGreen"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' [[ACE inhibitors]] should be started and continued indefinitely in all patients with [[EF|left ventricular ejection fraction]] less than or equal to 40% and in those with [[hypertension]], [[diabetes]], or [[chronic kidney disease]] unless contraindicated. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])'' <nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''2.''' [[ACE inhibitors]] should be started and continued indefinitely in patients who are not lower risk (lower risk defined as those with normal [[EF|left ventricular ejection fraction]] in whom cardiovascular risk factors are well controlled and [[Chronic stable angina revascularization percutaneous coronary intervention(PCI)|revascularization]] has been performed), unless contraindicated. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''3.''' [[Angiotensin receptor blockers]] are recommended for patients who have [[hypertension]], have indications for but are intolerant of [[ACE inhibitors]], have [[heart failure]], or have had a [[myocardial infarction]] with [[EF|left ventricular ejection fraction]] less than or equal to 40%. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])'' <nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''4.''' [[Aldosterone antagonist|Aldosterone blockade]] is recommended for use in [[MI|post-MI]] patients without significant [[Renal insufficiency|renal dysfunction]] (creatinine should be less than 2.5 mg per dL in men and less than 2.0 mg per dL in women) or [[hyperkalemia]] (potassium should be less than 5.0 mEq per L) who are already receiving therapeutic doses of an [[ACE inhibitor]] and a [[Chronic stable angina treatment beta blockers|beta blocker]], have a [[EF|left ventricular ejection fraction]] less than or equal to 40%, and have either [[diabetes]] or [[heart failure]]. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])'' <nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''5.''' [[ACE inhibitor]] in patients with [[coronary artery disease|CAD]]<nowiki>*</nowiki> who also have [[diabetes]] and/or [[left ventricular dysfunction|left ventricular systolic dysfunction]]. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])'' <nowiki>"</nowiki>
|}
{{cquote| <nowiki>*</nowiki> Significant [[Coronary artery disease|CAD]] by [[angiography]] or previous [[Myocardial infarction|MI]]. 
}}

{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LemonChiffon"| [[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIa]]
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' It is reasonable to use [[ACE inhibitors]] among lower-risk patients with mildly reduced or normal [[EF|left ventricular ejection fraction]] in whom cardiovascular risk factors are well controlled and [[Chronic stable angina revascularization percutaneous coronary intervention(PCI)|revascularization]] has been performed. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''2.''' [[ACE inhibitor]] in all patients with [[Coronary artery disease|CAD]]<nowiki>*</nowiki> or other vascular disease.''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
|}
{{cquote| <nowiki> *</nowiki> Significant [[Coronary artery disease|CAD]] by [[angiography]] or previous [[Myocardial infarction|MI]].
}}

{|class="wikitable"
|-
| colspan="1" style="text-align:center; background:LemonChiffon"| [[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIb]]
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' [[Angiotensin receptor blockers]] may be considered in combination with [[ACE inhibitors]] for [[heart failure]] due to [[Left ventricular dysfunction|left ventricular systolic dysfunction]]. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
|}

==ESC Guidelines- Pharmacological Therapy to Improve Prognosis in Patients with Stable Angina (DO NOT EDIT)<ref name="pmid16735367">{{cite journal| author=Fox K, Garcia MA, Ardissino D, Buszman P, Camici PG, Crea F et al.| title=Guidelines on the management of stable angina pectoris: executive summary: The Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology. | journal=Eur Heart J | year= 2006 | volume= 27 | issue= 11 | pages= 1341-81 | pmid=16735367 | doi=10.1093/eurheartj/ehl001 | pmc= |url=url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16735367 [http://www.escardio.org/guidelines-surveys/esc-guidelines/GuidelinesDocuments/guidelines-angina-FT.pdf]}} </ref>==

===Renin-Angiotensin-Aldosterone Receptor Blockers (DO NOT EDIT)<ref name="pmid16735367">{{cite journal| author=Fox K, Garcia MA, Ardissino D, Buszman P, Camici PG, Crea F et al.| title=Guidelines on the management of stable angina pectoris: executive summary: The Task Force on the Management of Stable Angina Pectoris of the European Society of Cardiology. | journal=Eur Heart J | year= 2006 | volume= 27 | issue= 11 | pages= 1341-81 | pmid=16735367 | doi=10.1093/eurheartj/ehl001 | pmc= |url=url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16735367 [http://www.escardio.org/guidelines-surveys/esc-guidelines/GuidelinesDocuments/guidelines-angina-FT.pdf]}} </ref>===

{| class="wikitable"
|-
| colspan="1" style="text-align:center; background:LightGreen"|[[European society of cardiology#Classes of Recommendations|Class I]]
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' [[ACE inhibitors|ACE-inhibitor therapy]] in patients with coincident indications for ACE-inhibition, such as [[hypertension]], [[heart failure]], [[Left ventricular dysfunction|LV dysfunction]], [[MI|prior MI]] with LV dysfunction, or [[diabetes]].  ''([[European society of cardiology#Level of Evidence|Level of Evidence: A]])'' <nowiki>"</nowiki>
|}

{| class="wikitable"
|-
| colspan="1" style="text-align:center; background:LemonChiffon"| [[European society of cardiology#Classes of Recommendations|Class IIa]]
|-
| bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' [[ACE inhibitors|ACE-inhibitor therapy]] in all patients with [[Chronic stable angina|angina]] and proven [[CAD|coronary disease]]. ''([[European society of cardiology#Level of Evidence|Level of Evidence: B]])'' <nowiki>"</nowiki>
|}

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