Unstable angina non ST elevation myocardial infarction anticoagulant therapy: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
mNo edit summary
 
(41 intermediate revisions by 8 users not shown)
Line 1: Line 1:
{{SI}}
__NOTOC__
{{WikiDoc Cardiology Network Infobox}}
{| class="infobox" style="float:right;"
{{CMG}}
|-
 
| [[File:Siren.gif|30px|link=Unstable angina/ NSTEMI resident survival guide]]|| <br> || <br>
'''Associate Editor-in-Chief:''' Smita Kohli, M.D.; [[Varun Kumar]], M.B.B.S.; [[Lakshmi Gopalakrishnan]], M.B.B.S.
| [[Unstable angina/ NSTEMI resident survival guide|'''Resident'''<br>'''Survival'''<br>'''Guide''']]
 
|}
{{Editor Join}}
{{Unstable angina / NSTEMI}}
{{CMG}}; '''Associate Editors-in-Chief:''' [[Varun Kumar]], M.B.B.S.; [[Lakshmi Gopalakrishnan]], M.B.B.S.; Smita Kohli, M.D.


==Overview==
==Overview==
Anticoagulation, traditionally with [[unfractionated heparin]] (UFH), is a cornerstone of therapy for patients with [[Unstable angina]]/[[NSTEMI]].  
Anticoagulation, traditionally with [[unfractionated heparin]] (UFH), is a cornerstone of therapy for patients with unstable angina]]/[[NSTEMI.  
Some of the agents available in this category include:
Some of the agents available in this category include [[unfractionated heparin]], [[low molecular weight heparin]], direct thrombin inhibitors (e.g., [[bivalirudin]]) factor Xa Inhibitors (e.g., [[fondaparinux]]),  and [[warfarin]]. These agents are also sometimes referred to as [[antithrombin]]s, although, it should be noted that they often inhibit one or more proteins in the coagulation cascade before [[thrombin]].
*[[unfractionated heparin]],  
*[[low molecular weight heparin]],
*Direct Thrombin Inhibitors (e.g.,[[bivalirudin]])
*Factor Xa Inhibitors (e.g.,[[fondaparinux]]),  and  
*[[warfarin]].  
These agents are also sometimes referred to as [[antithrombin]]s, although, it should be noted that they often inhibit one or more proteins in the coagulation cascade before [[thrombin]].


==Unfractionated Heparin(UFH)==
==Anticoagulant Therapy in UA/NSTEMI==
'''Mechanism of action:'''
You can read in greater detail about each of the therapies specifically in relation to unstable angina and NSTEMI, by clicking on the link for that therapy:
*[[Unfractionated heparin]] exerts its anticoagulant effect by potentiating the action of circulating [[antithrombin]], a proteolytic enzyme that inactivates factor IIa ([[thrombin]]), factor IXa, and factor Xa.
*[[Unstable angina / NSTEMI unfractionated heparin therapy |Unfractionated heparin]]  
*It prevents thrombus propagation but does not lyse existing thrombi.
*[[Unstable angina / NSTEMI low molecular weight heparin therapy |Low molecular weight heparin]]
*[[Unstable angina / NSTEMI direct thrombin inhibitors therapy |Direct thrombin inhibitors]]  
*[[Unstable angina / NSTEMI factor Xa inhibitors therapy |Factor Xa inhibitors]]
*[[Unstable angina / NSTEMI long term anticoagulation therapy |Long-term anticoagulation]]'''


'''Clinical trial data:'''
==2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes (DO NOT EDIT) <ref name=Guidelines> Ezra A. Amsterdam, MD, FACC; Nanette K. Wenger, MD et al.2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes.  A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. JACC. September 2014 (ahead of print) </ref>==
*A meta-analysis showed that in [[aspirin]]-treated patients with [[acute coronary syndrome]] without ST elevation, short-term [[unfractionated heparin]] or [[LMWH]] halves the risk of [[myocardial infarction]] or death<ref name="pmid10859038">{{cite journal | author = Eikelboom JW, Anand SS, Malmberg K, Weitz JI, Ginsberg JS, Yusuf S | title = Unfractionated heparin and low-molecular-weight heparin in acute coronary syndrome without ST elevation: a meta-analysis | journal = [[Lancet]] | volume = 355 | issue = 9219 | pages = 1936–42 | year = 2000 | month = June | pmid = 10859038 | doi = 10.1016/S0140-6736(00)02324-2 | url = http://linkinghub.elsevier.com/retrieve/pii/S0140-6736(00)02324-2 | accessdate = 2011-04-11}}</ref>.


'''Dosing:'''
===Initial Parenteral Anticoagulant Therapy in Patients With Definite NSTE-ACS===
*This is a short acting drug with an anticoagulation half life of 1.5hrs. Hence, frequent monitoring of the anticoagulant response using [[activated partial thromboplastin time]] (APTT) is recommended with titrations made according to a standardized nomogram aiming for an APTT range between 1.5 to 2 times control or 50 to 70 seconds .


'''Adverse effects:'''
{|class="wikitable"
*bleeding(specially with elevated [[APTT]])
|-
*[[heparin induced thrombocytopenia]]
| colspan="1" style="text-align:center; background:LightGreen"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]
|-
| bgcolor="LightGreen"|
<nowiki>"</nowiki>'''1.'''In patients with NSTE-ACS, anticoagulation, in addition to antiplatelet therapy, is recommended for all patients irrespective of initial treatment strategy. Treatment options include:


* [[Enoxaparin]]: 1 mg/kg subcutaneous (SC) every 12 hours (reduce dose to 1 mg/kg SC once daily in patients with [[creatinine]] clearance [CrCl] <30 mL/min), continued for the duration of hospitalization or until [[PCI]] is performed. An initial intravenous loading dose is 30 mg. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])''


==Low Molecular Weight Heparin(LMWH)==
* [[Bivalirudin]]: 0.10 mg/kg loading dose followed by 0.25 mg/kg per hour (only in patients managed with an early invasive strategy), continued until diagnostic [[angiography]] or [[PCI]], with only provisional use of GP IIb/IIIa inhibitor, provided the patient is also treated with DAPT. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''
'''Mechanism of benefit:'''
*[[LMWH]] combine factor IIa and factor Xa inhibition and thus inhibit both the action and generation of thrombin.  
*It has a number of advantages over [[UFH]] such as its greater anti-factor Xa activity inhibits thrombin generation more effectively, lower rate of [[thrombocytopenia]], high bioavailabiltiy, more consistent anticoagulant effect and no requirement of intensive lab monitoring.


'''Clinical trial data:'''
* [[Fondaparinux]]: 2.5 mg SC daily, continued for the duration of hospitalization or until [[PCI]] is performed. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''
*Results from TIMI 11B study<ref name="pmid10517729">{{cite journal |author=Antman EM, McCabe CH, Gurfinkel EP, Turpie AG, Bernink PJ, Salein D, Bayes De Luna A, Fox K, Lablanche JM, Radley D, Premmereur J, Braunwald E |title=Enoxaparin prevents death and cardiac ischemic events in unstable angina/non-Q-wave myocardial infarction. Results of the thrombolysis in myocardial infarction (TIMI) 11B trial |journal=[[Circulation]] |volume=100 |issue=15 |pages=1593–601 |year=1999 |month=October |pmid=10517729 |doi= |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=10517729 |accessdate=2011-04-11}}</ref> showed superiority of [[LMWH]] over [[UFH]] for reducing a composite of death and serious cardiac ischemic events during the acute management of [[Unstable angina]]/NQMI patients without causing a significant increase in the rate of major [[hemorrhage]].
*Results from SYNERGY trial<ref name="pmid15238590">{{cite journal |author=Ferguson JJ, Califf RM, Antman EM, Cohen M, Grines CL, Goodman S, Kereiakes DJ, Langer A, Mahaffey KW, Nessel CC, Armstrong PW, Avezum A, Aylward P, Becker RC, Biasucci L, Borzak S, Col J, Frey MJ, Fry E, Gulba DC, Guneri S, Gurfinkel E, Harrington R, Hochman JS, Kleiman NS, Leon MB, Lopez-Sendon JL, Pepine CJ, Ruzyllo W, Steinhubl SR, Teirstein PS, Toro-Figueroa L, White H |title=Enoxaparin vs unfractionated heparin in high-risk patients with non-ST-segment elevation acute coronary syndromes managed with an intended early invasive strategy: primary results of the SYNERGY randomized trial |journal=[[JAMA : the Journal of the American Medical Association]] |volume=292 |issue=1 |pages=45–54 |year=2004 |month=July |pmid=15238590 |doi=10.1001/jama.292.1.45 |url=http://jama.ama-assn.org/cgi/pmidlookup?view=long&pmid=15238590 |accessdate=2011-04-11}}</ref> revealed noninferiority of [[LMWH]] over [[UFH]] for the treatment of high-risk patients with non-ST-segment elevation [[ACS]]. However, both trials did show increased risk of major bleeding with [[LMWH]].
*A prospective analysis of the A to Z trial<ref name="pmid15451146">{{cite journal |author=de Lemos JA, Blazing MA, Wiviott SD, Brady WE, White HD, Fox KA, Palmisano J, Ramsey KE, Bilheimer DW, Lewis EF, Pfeffer M, Califf RM, Braunwald E |title=Enoxaparin versus unfractionated heparin in patients treated with tirofiban, aspirin and an early conservative initial management strategy: results from the A phase of the A-to-Z trial |journal=[[European Heart Journal]] |volume=25 |issue=19 |pages=1688–94 |year=2004 |month=October |pmid=15451146 |doi=10.1016/j.ehj.2004.06.028 |url=http://eurheartj.oxfordjournals.org/cgi/pmidlookup?view=long&pmid=15451146 |accessdate=2011-04-11}}</ref> showed that [[enoxaparin]] provided significant benefit over [[UFH]] in patients managed conservatively (who are typically on [[heparin]]/[[LMWH]] for at least 48 hours) but not in those with early invasive approach(who are taken to the catheterization laboratory within 48 hours and have their [[heparin]] discontinued thereafter).


'''Disadvantages of LMWH:'''
* If [[PCI]] is performed while the patient is on [[fondaparinux]], an additional anticoagulant with anti-IIa activity (either UFH or bivalirudin) should be administered because of the risk of catheter thrombosis. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''
*[[LMWH]] are more affected by renal dysfunction than [[UFH]], and the dose should be reduced in patients with a creatinine clearance <30 mL/min.
*Also, in the event of bleeding, the anticoagulant effect of [[UFH]] can be reversed more effectively with [[protamine]].


* [[UFH]] IV: initial loading dose of 60 IU/kg (maximum 4,000 IU) with initial infusion of 12 IU/kg per hour (maximum 1,000 IU/h) adjusted per activated partial thromboplastin time to maintain therapeutic anticoagulation according to the specific hospital protocol, continued for 48 hours or until PCI is performed. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowikI>
|}


==Direct Thrombin Inhibitors==
===PCI—General Considerations===
[[Hirudin]] which is the prototype of this class of drugs has been studied in multiple trials with mixed results. Other drugs in this class include [[bivalirudin]], [[argatroban]], efegatran and inogatran. [[Bivalirudin]] is a synthetic analog of [[hirudin]] that binds reversibly to [[thrombin]] and inhibits clot-bound thrombin.
====Anticoagulant Therapy in Patients Undergoing PCI====


'''Indications:'''
{|class="wikitable"
*Hirudin (lepirudin) is presently indicated by the US Food and Drug Administration only for anticoagulation in patients with [[heparin-induced thrombocytopenia]] and for the prophylaxis of [[deep vein thrombosis]] in patients undergoing hip replacement surgery.
|-
| colspan="1" style="text-align:center; background:LightGreen"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class I]]
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''1.''' An anticoagulant should be administered to patients with NSTE-ACS undergoing [[PCI]] to reduce the risk of intracoronary and catheter [[thrombus]] formation. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''2.''' Intravenous [[UFH]] is useful in patients with NSTE-ACS undergoing [[PCI]]. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''3.''' [[Bivalirudin]] is useful as an anticoagulant with or without prior treatment with [[UFH]] in patients with NSTE-ACS undergoing [[PCI]]. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''4.''' An additional dose of 0.3 mg/kg IV enoxaparin should be administered at the time of [[PCI]] to patients with NSTE-ACS who have received fewer than 2 therapeutic subcutaneous doses (e.g., 1 mg/kg SC) or received the last subcutaneous [[enoxaparin]] dose 8 to 12 hours before [[PCI]]. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''5.''' If [[PCI]] is performed while the patient is on [[fondaparinux]], an additional 85 IU/kg of [[UFH]] should be given intravenously immediately before [[PCI]] because of the risk of catheter [[thrombosis]] (60 IU/kg IV if a GP IIb/IIIa inhibitor used with [[UFH]] dosing based on the target-activated clotting time). ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''6.''' In patients with NSTE-ACS, anticoagulant therapy should be discontinued after [[PCI]] unless there is a compelling reason to continue such therapy. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|}


*[[Argatroban]] is another direct thrombin inhibitor that is approved for the management of patients with [[heparin-induced thrombocytopenia]].
{|class="wikitable"
|-
|colspan="1" style="text-align:center; background:LightCoral"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class III]] (No Benefit)
|-
|bgcolor="LightCoral"|<nowiki>"</nowiki>'''1.''' [[Fondaparinux]] should not be used as the sole anticoagulant to support [[PCI]] in patients with NSTEACS due to an increased risk of catheter [[thrombosis]]. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|}


'''Clinical trial data:'''
{|class="wikitable"
*The relative benefits of [[hirudin]] versus [[UFH]] in [[ACS]] patients was evaluated in the 12,142 patient in GUSTO-IIb trial<ref name="pmid8778585">{{cite journal |author= |title=A comparison of recombinant hirudin with heparin for the treatment of acute coronary syndromes. The Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) IIb investigators |journal=[[The New England Journal of Medicine]] |volume=335 |issue=11 |pages=775–82 |year=1996 |month=September |pmid=8778585 |doi=10.1056/NEJM199609123351103 |url=http://dx.doi.org/10.1056/NEJM199609123351103 |accessdate=2011-04-11}}</ref>. A reduction in risk for nonfatal [[MI]] was seen without increased risk of major bleeding.
|-
*TIMI 9B study failed to show any difference in outcomes in [[Hirudin]] verus [[heparin]] treated patients getting [[TPA]].
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIa]]
*The Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) trial<ref name="pmid17124018">{{cite journal |author=Stone GW, McLaurin BT, Cox DA, Bertrand ME, Lincoff AM, Moses JW, White HD, Pocock SJ, Ware JH, Feit F, Colombo A, Aylward PE, Cequier AR, Darius H, Desmet W, Ebrahimi R, Hamon M, Rasmussen LH, Rupprecht HJ, Hoekstra J, Mehran R, Ohman EM |title=Bivalirudin for patients with acute coronary syndromes |journal=[[The New England Journal of Medicine]] |volume=355 |issue=21 |pages=2203–16 |year=2006 |month=November |pmid=17124018 |doi=10.1056/NEJMoa062437 |url=http://dx.doi.org/10.1056/NEJMoa062437 |accessdate=2011-04-11}}</ref> randomized 13,819 patients with [[Unstable angina]]/[[NSTEMI]] to one of three treatments: [[UFH]], or [[enoxaparin]] plus a [[GP IIb/IIIa inhibitor]], or [[bivalirudin]] plus a [[GP IIb/IIIa inhibitor]], or [[bivalirudin]] alone. Patients were managed with an early invasive strategy and the primary endpoint was the composite of death, [[myocardial infarction]], unplanned revascularization for [[ischemia]], and major bleeding at 30 days. No differences were observed in the direct comparison of the anticoagulants i.e., between bivalirudin plus GP IIb/IIIa inhibitor and UFH/enoxaparin plus a GP IIb/IIIa inhibitor or bivalirudin alone. But for the bivalirudin alone group, when compared with the group receiving UFH/enoxaparin plus a GP IIb/IIIa inhibitor, there was decrease risk for bleeding. 
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' In patients with NSTE-ACS undergoing [[PCI]] who are at high risk of bleeding, it is reasonable to use [[bivalirudin]] monotherapy in preference to the combination of UFH and a GP IIb/IIIa receptor antagonist. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|}


'''Disadvantage of Direct Thrombin Inhibitors:'''
{|class="wikitable"
*Direct thrombin inhibitors lack a protamine-binding domain, hence it is not possible to reverse the effect with [[protamine]]. In the event of bleeding,discontinuation of their administration and, if needed, transfusion of coagulation factors (e.g., [[fresh frozen plasma]])is required.
|-
*In [[ACS]], the monovalent direct thrombin inhibitors(including argatroban) are ineffective anti-thrombotic agents compared with [[UFH]], and thus, [[argatroban]] should generally not be used in management of [[ACS]].
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIb]]
|-
|bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' Performance of [[PCI]] with [[enoxaparin]] may be reasonable in patients treated with upstream subcutaneous [[enoxaparin]] for NSTE-ACS. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|}


===Medical Regimen and Use of Medications at Discharge===
====Combined Oral Anticoagulant Therapy and Antiplatelet Therapy in Patients With NSTEACS====
{|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.''' The duration of triple antithrombotic therapy with a [[vitamin K antagonist]], [[aspirin]], and a P2Y12 receptor inhibitor in patients with NSTE-ACS should be minimized to the extent possible to limit the risk of [[bleeding]]. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|-
| bgcolor="LightGreen"|<nowiki>"</nowiki>'''2.''' [[Proton pump inhibitor]]s should be prescribed in patients with NSTE-ACS with a history of gastrointestinal bleeding who require triple antithrombotic therapy with a [[vitamin K antagonist]], [[aspirin]], and a P2Y12 receptor inhibitor. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|-
|}


==Factor Xa Inhibitors==
{|class="wikitable"
[[Fondaparinux]] is the prototype in this class of drug which is an indirect Xa inhibitor that requires antithrombin for its action.  
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIa]]
|-
| bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' [[Proton pump inhibitor]] use is reasonable in patients with NSTE-ACS without a known history of [[gastrointestinal bleeding]] who require triple antithrombotic therapy with a vitamin K antagonist, aspirin, and a P2Y12 receptor inhibitor. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|-
|}


'''Clinical trial data:'''
{|class="wikitable"
*The OASIS 5 and 6 trials<ref name="pmid18955665">{{cite journal |author=Mehta SR, Boden WE, Eikelboom JW, Flather M, Steg PG, Avezum A, Afzal R, Piegas LS, Faxon DP, Widimsky P, Budaj A, Chrolavicius S, Rupprecht HJ, Jolly S, Granger CB, Fox KA, Bassand JP, Yusuf S |title=Antithrombotic therapy with fondaparinux in relation to interventional management strategy in patients with ST- and non-ST-segment elevation acute coronary syndromes: an individual patient-level combined analysis of the Fifth and Sixth Organization to Assess Strategies in Ischemic Syndromes (OASIS 5 and 6) randomized trials |journal=[[Circulation]] |volume=118 |issue=20 |pages=2038–46 |year=2008 |month=November |pmid=18955665 |doi=10.1161/CIRCULATIONAHA.108.789479 |url=http://circ.ahajournals.org/cgi/pmidlookup?view=long&pmid=18955665 |accessdate=2011-04-11}}</ref> evaluated the use of [[fondaparinux]] in [[ACS]] and compared it with a [[heparin]]-based strategy. Results showed that compared to heparin based strategy, fondaparinux reduced mortality, ischemic events, and major bleeding across the full spectrum of [[acute coronary syndromes]] and was associated with a more favorable net clinical outcome in patients undergoing either an invasive or a conservative management strategy.
|-
*The OASIS-5 trial<ref name="pmid17964037">{{cite journal |author=Mehta SR, Granger CB, Eikelboom JW, Bassand JP, Wallentin L, Faxon DP, Peters RJ, Budaj A, Afzal R, Chrolavicius S, Fox KA, Yusuf S |title=Efficacy and safety of fondaparinux versus enoxaparin in patients with acute coronary syndromes undergoing percutaneous coronary intervention: results from the OASIS-5 trial |journal=[[Journal of the American College of Cardiology]] |volume=50 |issue=18 |pages=1742–51 |year=2007 |month=October |pmid=17964037 |doi=10.1016/j.jacc.2007.07.042 |url=http://linkinghub.elsevier.com/retrieve/pii/S0735-1097(07)02494-1 |accessdate=2011-04-11}}</ref> specifically compared [[fondaparinux]], administered at a relatively low dose, 2.5 mg subcutaneously, once daily with standard-dose [[enoxaparin]] in 20,078 patients with high-risk [[UA]]/[[NSTEMI]]. The rates of death, [[MI]], or refractory [[ischemia]] throughout the first 9 days were similar with [[fondaparinux]] and [[enoxaparin]]. Of note, however, the rate of major bleeding was almost 50 percent lower in the fondaparinux arm. By 30 days, mortality was significantly lower in the fondaparinux arm. However, in the subset of patients undergoing [[PCI]], fondaparinux was associated with more than a threefold increased risk of catheter-related thrombi.
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIb]]
|-
| bgcolor="LemonChiffon"|<nowiki>"</nowiki>'''1.''' Targeting oral anticoagulant therapy to a lower [[international normalized ratio]] (INR) (e.g., 2.0 to 2.5) may be reasonable in patients with NSTE-ACS managed with aspirin and a P2Y12 inhibitor. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: C]])''<nowiki>"</nowiki>
|-
|}


'''Disadvantage of Factor Xa Inhibitors:'''
==2011 ACCF/AHA Focused Update Incorporated Into the ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non -ST-Elevation Myocardial Infarction (DO NOT EDIT)<ref name="pmid21444888">{{cite journal| author=Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE et al.| title=2011 ACCF/AHA Focused Update Incorporated Into the ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. | journal=Circulation | year= 2011 | volume= 123 | issue= 18 | pages= e426-579 | pmid=21444888 | doi=10.1161/CIR.0b013e318212bb8b | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21444888  }} </ref>==
*[[fondaparinux]] lacks a protamine-binding domain, hence it is not possible to reverse the effect with [[protamine]]. In the event of bleeding,discontinuation of their administration and, if needed, transfusion of coagulation factors (e.g., [[fresh-frozen plasma]])is required.
===Anticoagulant Therapy (DO NOT EDIT)<ref name="pmid21444888">{{cite journal| author=Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE et al.| title=2011 ACCF/AHA Focused Update Incorporated Into the ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. | journal=Circulation | year= 2011 | volume= 123 | issue= 18 | pages= e426-579 | pmid=21444888 | doi=10.1161/CIR.0b013e318212bb8b | pmc= | url=http://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=21444888  }} </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.''' Anticoagulant therapy should be added to antiplatelet therapy in [[UA]] / [[NSTEMI]] patients as soon as possible after presentation.
|-
| bgcolor="LightGreen"|
'''a)''' For patients in whom an invasive strategy is selected, regimens with established efficacy at a ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])'' include [[enoxaparin]] and [[UFH]], and those with established efficacy at a ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' include [[bivalirudin]] and [[fondaparinux]].
|-
| bgcolor="LightGreen"|
'''b)''' For patients in whom a conservative strategy is selected, regimens using either [[enoxaparin]]<sup><nowiki>‡</nowiki></sup> or [[UFH]] ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: A]])'' or [[fondaparinux]] ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])'' have established efficacy. See also Class IIa recommendation below.
|-
| bgcolor="LightGreen"|
'''c)''' In patients in whom a conservative strategy is selected and who have an increased risk of bleeding, [[fondaparinux]] is preferable. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|}


==Long Term Anticoagulation==
{|class="wikitable"
[[Warfarin]] is the typical drug used for long term anticoagulation. However, its role, if any, in patients with [[UA]]/[[NSTEMI]] has not been clearly defined.  
|-
| colspan="1" style="text-align:center; background:LemonChiffon"|[[ACC AHA guidelines classification scheme#Classification of Recommendations|Class IIa]]
|-
| bgcolor="LemonChiffon"|
<nowiki>"</nowiki>'''1.''' For [[UA]] / [[NSTEMI]] patients in whom an initial conservative strategy is selected, [[enoxaparin]]<sup><nowiki>‡</nowiki></sup> or [[fondaparinux]] is preferable to [[UFH]] as [[anticoagulant therapy]], unless [[CABG]] is planned within 24 h. ''([[ACC AHA guidelines classification scheme#Level of Evidence|Level of Evidence: B]])''<nowiki>"</nowiki>
|}


'''Clinical trial data:'''
{{cquote|
*ASPECT 2 trial<ref name="pmid12126819">{{cite journal |author=van Es RF, Jonker JJ, Verheugt FW, Deckers JW, Grobbee DE |title=Aspirin and coumadin after acute coronary syndromes (the ASPECT-2 study): a randomised controlled trial |journal=Lancet |volume=360 |issue=9327 |pages=109–13 |year=2002 |month=July |pmid=12126819 |doi=10.1016/S0140-6736(02)09409-6 |url=}}</ref> showed that in patients recently admitted with [[ACS]], treatment with high-intensity oral anticoagulants or [[aspirin]] with medium-intensity oral anticoagulants was more effective than aspirin alone in reduction of subsequent cardiovascular events and death. However, similar benefit is seen with [[clopidogrel]] plus aspirin over aspirin alone, the lack of need for monitoring of the [[INR]], and the frequent use of [[PCI]] and stenting in the patient population in whom the need for clopidogrel is well established, the clinical use of aspirin plus warfarin is limited. Among patients without a coronary stent but with another indication for warfarin, such as chronic [[atrial fibrillation]], mechanical valve or severe [[left ventricular dysfunction]] who are at high risk of systemic [[embolization]], the combination of aspirin plus warfarin would be preferable as the long-term antithrombotic strategy.
<sup><nowiki>‡</nowiki></sup> Limited data are available for the use of other LMWHs (e.g., dalteparin) in UA/NSTEMI.}}
 
 
 
==ACC / AHA Guidelines for Anticoagulation Therapy (DO NOT EDIT)==
 
{{cquote| 
===Class I===
 
# Anticoagulant therapy should be added to [[antiplatelet therapy]] in [[UA]] / [[NSTEMI]] patients as soon as possible after presentation.
::a. For patients in whom an invasive strategy is selected, regimens with established efficacy at a ''Level of Evidence: A'' include [[enoxaparin]] and [[UFH]], and those with established efficacy at a ''Level of Evidence: B'' include [[bivalirudin]] and [[fondaparinux]].
::b. For patients in whom a conservative strategy is selected, regimens using either [[enoxaparin]] or [[UFH]] (Level of Evidence: A) or [[fondaparinux]] (Level of Evidence: B) have established efficacy.  
::c. In patients in whom a conservative strategy is selected and who have an increased risk of bleeding, [[fondaparinux]] is preferable. (Level of Evidence: B)  
 
===Class IIa===
 
# For [[UA]] / [[NSTEMI]] patients in whom an initial conservative strategy is selected, [[enoxaparin]] or [[fondaparinux]] is preferable to [[UFH]] as [[anticoagulant therapy]], unless [[CABG]] is planned within 24 h. (Level of Evidence: B)}}
 
 
==See Also==
* [[The Living Guidelines: UA/NSTEMI | The UA / NSTEMI Living Guidelines: Vote on current recommendations and suggest revisions to the guidelines]]
 
==Sources==
*The ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction <ref name="pmid17692738">{{cite journal |author=Anderson JL, Adams CD, Antman EM, ''et al'' |title=ACC/AHA 2007 guidelines for the management of patients with unstable angina/non-ST-Elevation myocardial infarction: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 2002 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction) developed in collaboration with the American College of Emergency Physicians, the Society for Cardiovascular Angiography and Interventions, and the Society of Thoracic Surgeons endorsed by the American Association of Cardiovascular and Pulmonary Rehabilitation and the Society for Academic Emergency Medicine |journal=JACC |volume=50 |issue=7 |pages=e1–e157 |year=2007 |month=August |pmid=17692738 |doi:10.1016/j.jacc.2007.02.013 |url=}}</ref>


==References==
==References==
{{reflist|2}}
{{Reflist|2}}
 
{{WH}}
{{SIB}}
{{WS}}


[[Category:Ischemic heart diseases]]
[[Category:Intensive care medicine]]
[[Category:Disease]]
[[Category:Cardiology]]
[[Category:Cardiology]]
{{WH}}
[[Category:Emergency medicine]]
{{WS}}
[[Category:Mature chapter]]
[[Category:Up-To-Date]]
[[Category:Up-To-Date cardiology]]
[[Category:Best pages]]

Latest revision as of 21:13, 5 December 2022
Resident
Survival
Guide

Acute Coronary Syndrome Main Page

Unstable angina / NSTEMI Microchapters

Home

Patient Information

Overview

Classification

Pathophysiology

Unstable Angina
Non-ST Elevation Myocardial Infarction

Differentiating Unstable Angina/Non-ST Elevation Myocardial Infarction from other Disorders

Epidemiology and Demographics

Risk Stratification

Natural History, Complications and Prognosis

Special Groups

Women
Heart Failure and Cardiogenic Shock
Perioperative NSTE-ACS Related to Noncardiac Surgery
Stress (Takotsubo) Cardiomyopathy
Diabetes Mellitus
Post CABG Patients
Older Adults
Chronic Kidney Disease
Angiographically Normal Coronary Arteries
Variant (Prinzmetal's) Angina
Substance Abuse
Cardiovascular "Syndrome X"

Diagnosis

History and Symptoms

Physical Examination

Laboratory Findings

Blood Studies
Biomarkers

Electrocardiogram

Chest X Ray

Echocardiography

Coronary Angiography

Treatment

Primary Prevention

Immediate Management

Anti-Ischemic and Analgesic Therapy

Cholesterol Management

Antitplatelet Therapy

Antiplatelet therapy recommendations
Aspirin
Thienopyridines
Glycoprotein IIb/IIIa Inhibitor

Anticoagulant Therapy

Additional Management Considerations for Antiplatelet and Anticoagulant Therapy

Risk Stratification Before Discharge for Patients With an Ischemia-Guided Strategy of NSTE-ACS

Mechanical Reperfusion

Initial Conservative Versus Initial Invasive Strategies
PCI
CABG

Complications of Bleeding and Transfusion

Discharge Care

Medical Regimen
Post-Discharge Follow-Up
Cardiac Rehabilitation

Long-Term Medical Therapy and Secondary Prevention

ICD implantation within 40 days of myocardial infarction

ICD within 90 days of revascularization

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Unstable angina non ST elevation myocardial infarction anticoagulant therapy On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Unstable angina non ST elevation myocardial infarction anticoagulant therapy

CDC onUnstable angina non ST elevation myocardial infarction anticoagulant therapy

Unstable angina non ST elevation myocardial infarction anticoagulant therapy in the news

Blogs on Unstable angina non ST elevation myocardial infarction anticoagulant therapy

to Hospitals Treating Unstable angina non ST elevation myocardial infarction anticoagulant therapy

Risk calculators and risk factors for Unstable angina non ST elevation myocardial infarction anticoagulant therapy

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editors-in-Chief: Varun Kumar, M.B.B.S.; Lakshmi Gopalakrishnan, M.B.B.S.; Smita Kohli, M.D.

Overview

Anticoagulation, traditionally with unfractionated heparin (UFH), is a cornerstone of therapy for patients with unstable angina]]/[[NSTEMI. Some of the agents available in this category include unfractionated heparin, low molecular weight heparin, direct thrombin inhibitors (e.g., bivalirudin) factor Xa Inhibitors (e.g., fondaparinux), and warfarin. These agents are also sometimes referred to as antithrombins, although, it should be noted that they often inhibit one or more proteins in the coagulation cascade before thrombin.

Anticoagulant Therapy in UA/NSTEMI

You can read in greater detail about each of the therapies specifically in relation to unstable angina and NSTEMI, by clicking on the link for that therapy:

2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes (DO NOT EDIT) [1]

Initial Parenteral Anticoagulant Therapy in Patients With Definite NSTE-ACS

Class I

"1.In patients with NSTE-ACS, anticoagulation, in addition to antiplatelet therapy, is recommended for all patients irrespective of initial treatment strategy. Treatment options include:

  • Enoxaparin: 1 mg/kg subcutaneous (SC) every 12 hours (reduce dose to 1 mg/kg SC once daily in patients with creatinine clearance [CrCl] <30 mL/min), continued for the duration of hospitalization or until PCI is performed. An initial intravenous loading dose is 30 mg. (Level of Evidence: A)
  • Bivalirudin: 0.10 mg/kg loading dose followed by 0.25 mg/kg per hour (only in patients managed with an early invasive strategy), continued until diagnostic angiography or PCI, with only provisional use of GP IIb/IIIa inhibitor, provided the patient is also treated with DAPT. (Level of Evidence: B)
  • If PCI is performed while the patient is on fondaparinux, an additional anticoagulant with anti-IIa activity (either UFH or bivalirudin) should be administered because of the risk of catheter thrombosis. (Level of Evidence: B)
  • UFH IV: initial loading dose of 60 IU/kg (maximum 4,000 IU) with initial infusion of 12 IU/kg per hour (maximum 1,000 IU/h) adjusted per activated partial thromboplastin time to maintain therapeutic anticoagulation according to the specific hospital protocol, continued for 48 hours or until PCI is performed. (Level of Evidence: B)"

PCI—General Considerations

Anticoagulant Therapy in Patients Undergoing PCI

Class I
"1. An anticoagulant should be administered to patients with NSTE-ACS undergoing PCI to reduce the risk of intracoronary and catheter thrombus formation. (Level of Evidence: C)"
"2. Intravenous UFH is useful in patients with NSTE-ACS undergoing PCI. (Level of Evidence: C)"
"3. Bivalirudin is useful as an anticoagulant with or without prior treatment with UFH in patients with NSTE-ACS undergoing PCI. (Level of Evidence: B)"
"4. An additional dose of 0.3 mg/kg IV enoxaparin should be administered at the time of PCI to patients with NSTE-ACS who have received fewer than 2 therapeutic subcutaneous doses (e.g., 1 mg/kg SC) or received the last subcutaneous enoxaparin dose 8 to 12 hours before PCI. (Level of Evidence: B)"
"5. If PCI is performed while the patient is on fondaparinux, an additional 85 IU/kg of UFH should be given intravenously immediately before PCI because of the risk of catheter thrombosis (60 IU/kg IV if a GP IIb/IIIa inhibitor used with UFH dosing based on the target-activated clotting time). (Level of Evidence: B)"
"6. In patients with NSTE-ACS, anticoagulant therapy should be discontinued after PCI unless there is a compelling reason to continue such therapy. (Level of Evidence: C)"
Class III (No Benefit)
"1. Fondaparinux should not be used as the sole anticoagulant to support PCI in patients with NSTEACS due to an increased risk of catheter thrombosis. (Level of Evidence: B)"
Class IIa
"1. In patients with NSTE-ACS undergoing PCI who are at high risk of bleeding, it is reasonable to use bivalirudin monotherapy in preference to the combination of UFH and a GP IIb/IIIa receptor antagonist. (Level of Evidence: B)"
Class IIb
"1. Performance of PCI with enoxaparin may be reasonable in patients treated with upstream subcutaneous enoxaparin for NSTE-ACS. (Level of Evidence: B)"

Medical Regimen and Use of Medications at Discharge

Combined Oral Anticoagulant Therapy and Antiplatelet Therapy in Patients With NSTEACS

Class I
"1. The duration of triple antithrombotic therapy with a vitamin K antagonist, aspirin, and a P2Y12 receptor inhibitor in patients with NSTE-ACS should be minimized to the extent possible to limit the risk of bleeding. (Level of Evidence: C)"
"2. Proton pump inhibitors should be prescribed in patients with NSTE-ACS with a history of gastrointestinal bleeding who require triple antithrombotic therapy with a vitamin K antagonist, aspirin, and a P2Y12 receptor inhibitor. (Level of Evidence: C)"
Class IIa
"1. Proton pump inhibitor use is reasonable in patients with NSTE-ACS without a known history of gastrointestinal bleeding who require triple antithrombotic therapy with a vitamin K antagonist, aspirin, and a P2Y12 receptor inhibitor. (Level of Evidence: C)"
Class IIb
"1. Targeting oral anticoagulant therapy to a lower international normalized ratio (INR) (e.g., 2.0 to 2.5) may be reasonable in patients with NSTE-ACS managed with aspirin and a P2Y12 inhibitor. (Level of Evidence: C)"

2011 ACCF/AHA Focused Update Incorporated Into the ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non -ST-Elevation Myocardial Infarction (DO NOT EDIT)[2]

Anticoagulant Therapy (DO NOT EDIT)[2]

Class I

"1. Anticoagulant therapy should be added to antiplatelet therapy in UA / NSTEMI patients as soon as possible after presentation.

a) For patients in whom an invasive strategy is selected, regimens with established efficacy at a (Level of Evidence: A) include enoxaparin and UFH, and those with established efficacy at a (Level of Evidence: B) include bivalirudin and fondaparinux.

b) For patients in whom a conservative strategy is selected, regimens using either enoxaparin‡ or UFH (Level of Evidence: A) or fondaparinux (Level of Evidence: B) have established efficacy. See also Class IIa recommendation below.

c) In patients in whom a conservative strategy is selected and who have an increased risk of bleeding, fondaparinux is preferable. (Level of Evidence: B)"

Class IIa

"1. For UA / NSTEMI patients in whom an initial conservative strategy is selected, enoxaparin‡ or fondaparinux is preferable to UFH as anticoagulant therapy, unless CABG is planned within 24 h. (Level of Evidence: B)"

“

‡ Limited data are available for the use of other LMWHs (e.g., dalteparin) in UA/NSTEMI.

”

References

  1. ↑ Ezra A. Amsterdam, MD, FACC; Nanette K. Wenger, MD et al.2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes. A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. JACC. September 2014 (ahead of print)
  2. ↑ 2.0 2.1 Anderson JL, Adams CD, Antman EM, Bridges CR, Califf RM, Casey DE; et al. (2011). "2011 ACCF/AHA Focused Update Incorporated Into the ACC/AHA 2007 Guidelines for the Management of Patients With Unstable Angina/Non-ST-Elevation Myocardial Infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines". Circulation. 123 (18): e426–579. doi:10.1161/CIR.0b013e318212bb8b. PMID 21444888.

Template:WH Template:WS

Retrieved from "https://www.wikidoc.org/index.php?title=Unstable_angina_non_ST_elevation_myocardial_infarction_anticoagulant_therapy&oldid=1731688"