Chronic anticoagulation after acute coronary syndromes
- Gregory YH Lip, MD, FRCPE, FESC, FACC
Gregory YH Lip, MD, FRCPE, FESC, FACC
- Professor of Cardiovascular Medicine
- The University of Birmingham, UK
- Section Editors
- Freek Verheugt, MD, FACC, FESC
Freek Verheugt, MD, FACC, FESC
- Section Editor — Coronary Heart Disease
- Onze Lieve Vrouwe Gasthuis, Netherlands
- Christopher P Cannon, MD
Christopher P Cannon, MD
- Section Editor — Coronary Heart Disease
- Professor of Medicine
- Harvard Medical School
In some patients with an acute coronary syndrome (ACS) (see "Criteria for the diagnosis of acute myocardial infarction", section on 'Acute coronary syndrome'), chronic oral anticoagulation is required to lower the risk of systemic (arterial) thromboembolism, such as those with atrial fibrillation, left ventricular systolic dysfunction or thrombus, or prosthetic heart valves. (See "Atrial fibrillation: Anticoagulant therapy to prevent embolization" and "Antithrombotic therapy in patients with heart failure" and "Antithrombotic therapy for prosthetic heart valves: Indications" and "Left ventricular thrombus after acute myocardial infarction", section on 'Prevention of embolic events'.)
ACS patients are routinely treated with aspirin and a P2Y12 receptor blocker (eg, clopidogrel, prasugrel, or ticagrelor) to decrease the risk of recurrent events (See "Antiplatelet agents in acute non-ST elevation acute coronary syndromes", section on 'Summary and recommendations' and "Antiplatelet agents in acute ST elevation myocardial infarction", section on 'Summary and recommendations'.) Thus, those who also require oral anticoagulation are discharged on triple oral anticoagulant therapy (TOAT). (See "Antithrombotic therapy after coronary stenting in patients receiving long-term anticoagulation".)
The issue of whether chronic anticoagulant therapy reduces the risk of recurrent cardiovascular events, such as myocardial infarction (MI) or cardiac death, after ACS has been evaluated in clinical trials. The rationale for a potential role of chronic anticoagulant therapy in this setting is based on the following two pieces of information:
●The high rates of recurrent ischemic events after ACS due, at least in part, to a persistent thrombotic risk within the coronary circulation. This thrombotic risk stems from heightened platelet reactivity, an increase in activity of some or all of the elements of the coagulation cascade, or both. (See "Overview of hemostasis".)
●The proven efficacy of long-term antithrombotic therapy with dual antiplatelet therapy in reducing recurrent ischemic events in most patients with an ACS. (See "Overview of the acute management of non-ST elevation acute coronary syndromes" and "Overview of the acute management of ST-elevation myocardial infarction".)To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Williams MJ, Morison IM, Parker JH, Stewart RA. Progression of the culprit lesion in unstable coronary artery disease with warfarin and aspirin versus aspirin alone: preliminary study. J Am Coll Cardiol 1997; 30:364.
- Merlini PA, Bauer KA, Oltrona L, et al. Persistent activation of coagulation mechanism in unstable angina and myocardial infarction. Circulation 1994; 90:61.
- Ueda Y, Asakura M, Yamaguchi O, et al. The healing process of infarct-related plaques. Insights from 18 months of serial angioscopic follow-up. J Am Coll Cardiol 2001; 38:1916.
- Borissoff JI, Spronk HM, ten Cate H. The hemostatic system as a modulator of atherosclerosis. N Engl J Med 2011; 364:1746.
- Williams MJ, Stewart RA. Coronary artery flow ten weeks after myocardial infarction or unstable angina: effects of combined warfarin and aspirin therapy. Int J Cardiol 1999; 69:19.
- Andreotti F, Testa L, Biondi-Zoccai GG, Crea F. Aspirin plus warfarin compared to aspirin alone after acute coronary syndromes: an updated and comprehensive meta-analysis of 25,307 patients. Eur Heart J 2006; 27:519.
- Rothberg MB, Celestin C, Fiore LD, et al. Warfarin plus aspirin after myocardial infarction or the acute coronary syndrome: meta-analysis with estimates of risk and benefit. Ann Intern Med 2005; 143:241.
- E.P.S.I.M. Research Group. A controlled comparison of aspirin and oral anticoagulants in prevention of death after myocardial infarction. N Engl J Med 1982; 307:701.
- Breddin K, Loew D, Lechner K, et al. The German-Austrian aspirin trial: a comparison of acetylsalicylic acid, placebo and phenprocoumon in secondary prevention of myocardial infarction. On behalf of the German-Austrian Study Group. Circulation 1980; 62:V63.
- Effect of long-term oral anticoagulant treatment on mortality and cardiovascular morbidity after myocardial infarction. Anticoagulants in the Secondary Prevention of Events in Coronary Thrombosis (ASPECT) Research Group. Lancet 1994; 343:499.
- Smith P, Arnesen H, Holme I. The effect of warfarin on mortality and reinfarction after myocardial infarction. N Engl J Med 1990; 323:147.
- A double-blind trial to assess long-term oral anticoagulant therapy in elderly patients after myocardial infarction. Report of the Sixty Plus Reinfarction Study Research Group. Lancet 1980; 2:989.
- Hurlen M, Abdelnoor M, Smith P, et al. Warfarin, aspirin, or both after myocardial infarction. N Engl J Med 2002; 347:969.
- van Es RF, Jonker JJ, Verheugt FW, et al. Aspirin and coumadin after acute coronary syndromes (the ASPECT-2 study): a randomised controlled trial. Lancet 2002; 360:109.
- Meijer A, Verheugt FW, Werter CJ, et al. Aspirin versus coumadin in the prevention of reocclusion and recurrent ischemia after successful thrombolysis: a prospective placebo-controlled angiographic study. Results of the APRICOT Study. Circulation 1993; 87:1524.
- Julian DG, Chamberlain DA, Pocock SJ. A comparison of aspirin and anticoagulation following thrombolysis for myocardial infarction (the AFTER study): a multicentre unblinded randomised clinical trial. BMJ 1996; 313:1429.
- Fiore LD, Ezekowitz MD, Brophy MT, et al. Department of Veterans Affairs Cooperative Studies Program Clinical Trial comparing combined warfarin and aspirin with aspirin alone in survivors of acute myocardial infarction: primary results of the CHAMP study. Circulation 2002; 105:557.
- Brouwer MA, van den Bergh PJ, Aengevaeren WR, et al. Aspirin plus coumarin versus aspirin alone in the prevention of reocclusion after fibrinolysis for acute myocardial infarction: results of the Antithrombotics in the Prevention of Reocclusion In Coronary Thrombolysis (APRICOT)-2 Trial. Circulation 2002; 106:659.
- Randomised double-blind trial of fixed low-dose warfarin with aspirin after myocardial infarction. Coumadin Aspirin Reinfarction Study (CARS) Investigators. Lancet 1997; 350:389.
- Herlitz J, Holm J, Peterson M, et al. Effect of fixed low-dose warfarin added to aspirin in the long term after acute myocardial infarction; the LoWASA Study. Eur Heart J 2004; 25:232.
- Effects of long-term, moderate-intensity oral anticoagulation in addition to aspirin in unstable angina. The Organization to Assess Strategies for Ischemic Syndromes (OASIS) Investigators. J Am Coll Cardiol 2001; 37:475.
- Oldgren J, Budaj A, Granger CB, et al. Dabigatran vs. placebo in patients with acute coronary syndromes on dual antiplatelet therapy: a randomized, double-blind, phase II trial. Eur Heart J 2011; 32:2781.
- Alexander JH, Lopes RD, James S, et al. Apixaban with antiplatelet therapy after acute coronary syndrome. N Engl J Med 2011; 365:699.
- Chesebro JH, Knatterud G, Roberts R, et al. Thrombolysis in Myocardial Infarction (TIMI) Trial, Phase I: A comparison between intravenous tissue plasminogen activator and intravenous streptokinase. Clinical findings through hospital discharge. Circulation 1987; 76:142.
- Mega JL, Braunwald E, Wiviott SD, et al. Rivaroxaban in patients with a recent acute coronary syndrome. N Engl J Med 2012; 366:9.
- Mega JL, Braunwald E, Murphy SA, et al. Rivaroxaban in patients stabilized after a ST-segment elevation myocardial infarction: results from the ATLAS ACS-2-TIMI-51 trial (Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects with Acute Coronary Syndrome-Thrombolysis In Myocardial Infarction-51). J Am Coll Cardiol 2013; 61:1853.
- Gibson CM, Chakrabarti AK, Mega J, et al. Reduction of stent thrombosis in patients with acute coronary syndromes treated with rivaroxaban in ATLAS-ACS 2 TIMI 51. J Am Coll Cardiol 2013; 62:286.
- Gibson CM, Mehran R, Bode C, et al. Prevention of Bleeding in Patients with Atrial Fibrillation Undergoing PCI. N Engl J Med 2016; 375:2423.
- Dewilde WJ, Oirbans T, Verheugt FW, et al. Use of clopidogrel with or without aspirin in patients taking oral anticoagulant therapy and undergoing percutaneous coronary intervention: an open-label, randomised, controlled trial. Lancet 2013; 381:1107.
- Ohman EM, Roe MT, Steg PG, et al. Clinically significant bleeding with low-dose rivaroxaban versus aspirin, in addition to P2Y12 inhibition, in acute coronary syndromes (GEMINI-ACS-1): a double-blind, multicentre, randomised trial. Lancet 2017.
- Komócsi A, Vorobcsuk A, Kehl D, Aradi D. Use of new-generation oral anticoagulant agents in patients receiving antiplatelet therapy after an acute coronary syndrome: systematic review and meta-analysis of randomized controlled trials. Arch Intern Med 2012; 172:1537.
- Mega JL, Braunwald E, Mohanavelu S, et al. Rivaroxaban versus placebo in patients with acute coronary syndromes (ATLAS ACS-TIMI 46): a randomised, double-blind, phase II trial. Lancet 2009; 374:29.
- Lip GY, Windecker S, Huber K, et al. Management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary or valve interventions: a joint consensus document of the European Society of Cardiology Working Group on Thrombosis, European Heart Rhythm Association (EHRA), European Association of Percutaneous Cardiovascular Interventions (EAPCI) and European Association of Acute Cardiac Care (ACCA) endorsed by the Heart Rhythm Society (HRS) and Asia-Pacific Heart Rhythm Society (APHRS). Eur Heart J 2014; 35:3155.
- 2012 Writing Committee Members, Jneid H, Anderson JL, et al. 2012 ACCF/AHA focused update of the guideline for the management of patients with unstable angina/Non-ST-elevation myocardial infarction (updating the 2007 guideline and replacing the 2011 focused update): a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. Circulation 2012; 126:875.
- Vandvik PO, Lincoff AM, Gore JM, et al. Primary and secondary prevention of cardiovascular disease: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest 2012; 141:e637S.
- O'Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2013; 127:529.
- O'Gara PT, Kushner FG, Ascheim DD, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Circulation 2013; 127:e362.
- BIOLOGIC PLAUSIBILITY
- PATIENTS WITHOUT OTHER INDICATIONS FOR CHRONIC ANTICOAGULATION
- - Meta-analyses
- - Randomized trials
- - Patients taking dual antiplatelet therapy
- - Patients not taking a platelet P2Y12 receptor blocker
- PATIENTS WITH INDICATIONS FOR CHRONIC ANTICOAGULATION
- Stented patients
- Non-stented patients
- RECOMMENDATIONS OF OTHERS
- BLEEDING RISK
- SOCIETY GUIDELINE LINKS
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS