Anticoagulant therapy in non-ST elevation acute coronary syndromes
- Donald Cutlip, MD
Donald Cutlip, MD
- Section Editor — Interventional Cardiology
- Professor of Medicine
- Harvard Medical School
- Beth Israel Deaconess Medical Center
- A Michael Lincoff, MD
A Michael Lincoff, MD
- Director, Center for Clinical Research
- Professor of Medicine
- Cleveland Clinic Lerner College of Medicine of Case Western Reserve University
- Section Editors
- Christopher P Cannon, MD
Christopher P Cannon, MD
- Section Editor — Coronary Heart Disease
- Professor of Medicine
- Harvard Medical School
- Freek Verheugt, MD, FACC, FESC
Freek Verheugt, MD, FACC, FESC
- Section Editor — Coronary Heart Disease
- Onze Lieve Vrouwe Gasthuis, Netherlands
Acute myocardial infarction results from rupture of an atherosclerotic plaque, which leads to intraluminal thrombosis. Intraluminal thrombus impairs distal blood flow and may lead to myocardial ischemia or infarction. Intraluminal hemostasis is a dynamic process involving both clot formation and intrinsic fibrinolysis. The goal of antithrombotic therapy (the combination of anticoagulant and antiplatelet therapy) is to prevent clot extension and reformation in cases where the clot has undergone fibrinolysis either by intrinsic mechanisms, fibrinolytic treatment, or mechanical means. (See "The role of the vulnerable plaque in acute coronary syndromes" and "Overview of hemostasis".)
This topic will review the evidence that supports the use of parenteral anticoagulant therapy in all patients with acute non-ST elevation acute coronary syndromes (NSTEACS), which include both unstable angina and acute non-ST elevation myocardial infarction. The topic will provide recommendations for its use according to whether the patient receives reperfusion with percutaneous coronary intervention or no reperfusion therapy. Information regarding anticoagulant agents in ST-elevation myocardial infarction and the role of antiplatelet therapy in NSTEACS is found elsewhere. (See "Anticoagulant therapy in acute ST elevation myocardial infarction" and "Antiplatelet agents in acute non-ST elevation acute coronary syndromes".)
CLASSIFICATION OF ANTICOAGULANT AGENTS
There are three classes of anticoagulants that have been evaluated in the management of acute coronary syndromes:
●The heparins, including unfractionated heparin (UFH) and the low molecular weight heparins (LMWH), are indirect thrombin inhibitors that complex with antithrombin (AT, formerly known as AT III) and convert AT from a slow to a rapid inactivator of thrombin, factor Xa, and to a lesser extent, factors XIIa, XIa, and IXa. (See "Overview of hemostasis" and "Heparin and LMW heparin: Dosing and adverse effects".)
There are a few limitations to UFH therapy in patients with acute myocardial infarction. One potential issue is binding to circulating plasma proteins, which renders inter- and intra-patient dosing unpredictable and requires continuous intravenous rather than subcutaneous dosing for consistent anticoagulant effect. The propensity to develop heparin-induced thrombocytopenia is another limitation. (See "Clinical presentation and diagnosis of heparin-induced thrombocytopenia".)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:
- Comparison of two treatment durations (6 days and 14 days) of a low molecular weight heparin with a 6-day treatment of unfractionated heparin in the initial management of unstable angina or non-Q wave myocardial infarction: FRAX.I.S. (FRAxiparine in Ischaemic Syndrome). Eur Heart J 1999; 20:1553.
- Michalis LK, Katsouras CS, Papamichael N, et al. Enoxaparin versus tinzaparin in non-ST-segment elevation acute coronary syndromes: the EVET trial. Am Heart J 2003; 146:304.
- Katsouras C, Michalis LK, Papamichael N, et al. Enoxaparin versus tinzaparin in non-ST-segment elevation acute coronary syndromes: results of the enoxaparin versus tinzaparin (EVET) trial at 6 months. Am Heart J 2005; 150:385.
- Klein W, Buchwald A, Hillis SE, et al. Comparison of low-molecular-weight heparin with unfractionated heparin acutely and with placebo for 6 weeks in the management of unstable coronary artery disease. Fragmin in unstable coronary artery disease study (FRIC). Circulation 1997; 96:61.
- Long-term low-molecular-mass heparin in unstable coronary-artery disease: FRISC II prospective randomised multicentre study. FRagmin and Fast Revascularisation during InStability in Coronary artery disease. Investigators. Lancet 1999; 354:701.
- Lefkovits J, Topol EJ. Direct thrombin inhibitors in cardiovascular medicine. Circulation 1994; 90:1522.
- Direct Thrombin Inhibitor Trialists' Collaborative Group. Direct thrombin inhibitors in acute coronary syndromes: principal results of a meta-analysis based on individual patients' data. Lancet 2002; 359:294.
- Eikelboom JW, Anand SS, Malmberg K, et al. Unfractionated heparin and low-molecular-weight heparin in acute coronary syndrome without ST elevation: a meta-analysis. Lancet 2000; 355:1936.
- Low-molecular-weight heparin during instability in coronary artery disease, Fragmin during Instability in Coronary Artery Disease (FRISC) study group. Lancet 1996; 347:561.
- Cohen M, Demers C, Gurfinkel EP, et al. A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study Group. N Engl J Med 1997; 337:447.
- Berkowitz SD, Stinnett S, Cohen M, et al. Prospective comparison of hemorrhagic complications after treatment with enoxaparin versus unfractionated heparin for unstable angina pectoris or non-ST-segment elevation acute myocardial infarction. Am J Cardiol 2001; 88:1230.
- Goodman SG, Cohen M, Bigonzi F, et al. Randomized trial of low molecular weight heparin (enoxaparin) versus unfractionated heparin for unstable coronary artery disease: one-year results of the ESSENCE Study. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q Wave Coronary Events. J Am Coll Cardiol 2000; 36:693.
- Antman EM, McCabe CH, Gurfinkel EP, et al. 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. Circulation 1999; 100:1593.
- Morrow DA, Antman EM, Tanasijevic M, et al. Cardiac troponin I for stratification of early outcomes and the efficacy of enoxaparin in unstable angina: a TIMI-11B substudy. J Am Coll Cardiol 2000; 36:1812.
- Blazing MA, de Lemos JA, White HD, et al. Safety and efficacy of enoxaparin vs unfractionated heparin in patients with non-ST-segment elevation acute coronary syndromes who receive tirofiban and aspirin: a randomized controlled trial. JAMA 2004; 292:55.
- Ferguson JJ, Califf RM, Antman EM, et al. 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. JAMA 2004; 292:45.
- Mahaffey KW, Cohen M, Garg J, et al. High-risk patients with acute coronary syndromes treated with low-molecular-weight or unfractionated heparin: outcomes at 6 months and 1 year in the SYNERGY trial. JAMA 2005; 294:2594.
- Erlinge D, Omerovic E, Fröbert O, et al. Bivalirudin versus Heparin Monotherapy in Myocardial Infarction. N Engl J Med 2017; 377:1132.
- Stone GW, McLaurin BT, Cox DA, et al. Bivalirudin for patients with acute coronary syndromes. N Engl J Med 2006; 355:2203.
- Stone GW, White HD, Ohman EM, et al. Bivalirudin in patients with acute coronary syndromes undergoing percutaneous coronary intervention: a subgroup analysis from the Acute Catheterization and Urgent Intervention Triage strategy (ACUITY) trial. Lancet 2007; 369:907.
- Kastrati A, Neumann FJ, Schulz S, et al. Abciximab and heparin versus bivalirudin for non-ST-elevation myocardial infarction. N Engl J Med 2011; 365:1980.
- Valgimigli M, Frigoli E, Leonardi S, et al. Bivalirudin or Unfractionated Heparin in Acute Coronary Syndromes. N Engl J Med 2015; 373:997.
- Fifth Organization to Assess Strategies in Acute Ischemic Syndromes Investigators, Yusuf S, Mehta SR, et al. Comparison of fondaparinux and enoxaparin in acute coronary syndromes. N Engl J Med 2006; 354:1464.
- Fox KA, Bassand JP, Mehta SR, et al. Influence of renal function on the efficacy and safety of fondaparinux relative to enoxaparin in non ST-segment elevation acute coronary syndromes. Ann Intern Med 2007; 147:304.
- Mehta SR, Granger CB, Eikelboom JW, et al. Efficacy and safety of fondaparinux versus enoxaparin in patients with acute coronary syndromes undergoing percutaneous coronary intervention: results from the OASIS-5 trial. J Am Coll Cardiol 2007; 50:1742.
- Jolly SS, Faxon DP, Fox KA, et al. Efficacy and safety of fondaparinux versus enoxaparin in patients with acute coronary syndromes treated with glycoprotein IIb/IIIa inhibitors or thienopyridines: results from the OASIS 5 (Fifth Organization to Assess Strategies in Ischemic Syndromes) trial. J Am Coll Cardiol 2009; 54:468.
- FUTURA/OASIS-8 Trial Group, Steg PG, Jolly SS, et al. Low-dose vs standard-dose unfractionated heparin for percutaneous coronary intervention in acute coronary syndromes treated with fondaparinux: the FUTURA/OASIS-8 randomized trial. JAMA 2010; 304:1339.
- Bittl JA, Strony J, Brinker JA, et al. Treatment with bivalirudin (Hirulog) as compared with heparin during coronary angioplasty for unstable or postinfarction angina. Hirulog Angioplasty Study Investigators. N Engl J Med 1995; 333:764.
- Stone GW, Witzenbichler B, Guagliumi G, et al. Bivalirudin during primary PCI in acute myocardial infarction. N Engl J Med 2008; 358:2218.
- Lincoff AM, Bittl JA, Harrington RA, et al. Bivalirudin and provisional glycoprotein IIb/IIIa blockade compared with heparin and planned glycoprotein IIb/IIIa blockade during percutaneous coronary intervention: REPLACE-2 randomized trial. JAMA 2003; 289:853.
- Martel N, Lee J, Wells PS. Risk for heparin-induced thrombocytopenia with unfractionated and low-molecular-weight heparin thromboprophylaxis: a meta-analysis. Blood 2005; 106:2710.
- Amsterdam EA, Wenger NK, Brindis RG, et al. 2014 AHA/ACC guideline for the management of patients with non-ST-elevation acute coronary syndromes: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation 2014; 130:2354.
- Roffi M, Patrono C, Collet JP, et al. 2015 ESC Guidelines for the management of acute coronary syndromes in patients presenting without persistent ST-segment elevation: Task Force for the Management of Acute Coronary Syndromes in Patients Presenting without Persistent ST-Segment Elevation of the European Society of Cardiology (ESC). Eur Heart J 2016; 37:267.
- CLASSIFICATION OF ANTICOAGULANT AGENTS
- OUR APPROACH
- CONSERVATIVE APPROACH
- INVASIVE APPROACH
- UFH compared with enoxaparin
- UFH compared with bivalirudin
- ANTICOAGULANT USE
- Heparin-induced thrombocytopenia
- RECOMMENDATIONS OF OTHERS
- SOCIETY GUIDELINE LINKS
- SUMMARY AND RECOMMENDATIONS