Warfarin and Aspirin Versus Aspirin Alone in Patients with Acute Myocardial Infarction: A Pilot Study

Abstract

The benefits of anticoagulant therapy and antiplatelet agents in secondary prevention of myocardial infarction (MI) are well known. Administration of combined warfarin and aspirin (ASA) has not been well studied. The objective of this study was to compare the effect of coadministration of warfarin and ASA with administration of ASA alone on outcome of patients after MI. One hundred forty age- and sex-matched survivors of MI were randomized to receive either 100 mg/day ASA plus enough warfarin to reach a target: international normalized ratio of 2.5 (range: 2-3) (group A, n = 70), or only 100 mg/day ASA (group B, n = 70). The patients were examined for several variables including development of hemorrhage, reinfarction, and rehospitalization for 1 year post MI. Of the variables studied, minor hemorrhagic episodes were observed significantly (p = 0.002) more in group A than in group B patients. Rehospitalization and reinfarction rates, although occurring with lower frequencies in group A than in group B, did not reach the statistical significance level. In postmyocardial infarction patients, warfarin plus ASA did not provide a clinical benefit beyond that achievable with aspirin monotherapy, and for the observed markedly higher incidence of minor hemorrhage in combination therapy, antiplatelet therapy alone seems to be a more reasonable approach.

Get full access to this article

View all access options for this article.

References

American Heart Association : Heart and Stroke Facts: 2000 Statistical Supplement Dallas: American Heart Association, 2000.

Braunwald E. , Fauci A. , Kasper D., et al : Acute myocardial infarction In: Harrison's Principles of Internal Medicine, ed. 15, ed. by Antman EM, et al. New York: McGraw-Hill, 2001, pp 1386-1399.

Randomised double-blind trial of fixed low-dose warfarin with aspirin after myocardial infarction.

Coumadin Aspirin Reinfarction Study (CARS) Investigators

Lancet 350:389-396, 1997.

Collaborative overview of randomised trials of antiplatelet therapy. I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients.

Antiplatelet Trialists' Collaboration

Br Med J 308:81-106, 1994.

Van Es RF , Jonker JJ , Verheugt FW, et al : Aspirin and coumadin after acute coronary syndromes (the ASPECT-2 study) : A randomized controlled trial Lancet 360:109-113, 2002.

Fiore LD , Ezekowitz MD , Brophy MT, et al : Clinical trial comparing combined warfarin and aspirin with aspirin alone in survivors of acute myocardial infarction : Primary results of the CHAMP study Circulation 105:557-563, 2002.

Huynh T. , Theroux P. , Bogaty P., et al : Aspirin, warfarin, or the combination for secondary prevention of coronary events in patients with acute coronary syndromes and prior coronary artery bypass surgery Circulation 103:3069-3074, 2001.

Braunwald E. , Zipes D. , Libby P. : Hemostasis, thrombosis, fibrinolysis and cardiovascular disease In: Heart Disease, ed. 5, ed. by Fuster V, Verstrate M. Philadelphia : WB Saunders , 1997, p 1827.

Smith P. , Arnesen H. , Holme I., et al : The effect of warfarin on mortality and reinfarction after myocardial infarction N Engl J Med 323:147-152, 1990.

10.

Effect of long-term oral anticoagulant treatment on mortality and cardiovascular morbidity after myocardial infarction.

The ASPECT Research Group

Lancet 343:499-503, 1994.

11.

Goodman SG , Langer A. , Durica SS, et al : Safety and anticoagulation effect of low-dose combination of warfarin and aspirin in clinically stable coronary artery disease. Coumadin Aspirin Reinfarction Study (CARS) Group Am J Cardiol 74:657-661, 1994.

12.

O'Connor CM , Gattis WA , Hellkamp AS, et al : Comparison of two aspirin doses on ischemic stroke in post-myocardial infarction patients in the warfarin (Coumadin) Aspirin Reinfarction study (CARS) Am J Cardiol 88:541-546, 2001.

13.

Brouwer MA , van den Bergh PJ , Aengevaeran 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 106:659-665, 2002.