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Circulation. 2002;106:659-665
Published online before print July 15, 2002, doi: 10.1161/01.CIR.0000024408.81821.32
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(Circulation. 2002;106:659.)
© 2002 American Heart Association, Inc.

Clinical Investigation and Reports

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

Marc A. Brouwer, MD; Paul J.P.C. van den Bergh, MD; Wim R.M. Aengevaeren, MD, PhD; Gerrit Veen, MD, PhD; Hans E. Luijten, MD; Don P. Hertzberger, MD; Ad J. van Boven, MD, PhD; Ralf P.J.W. Vromans, MD; Gérard J.H. Uijen, PhD; Freek W.A. Verheugt, MD, PhD

From the Interuniversity Cardiology Institute of the Netherlands, Nijmegen.

Correspondence to Freek W.A. Verheugt, MD, PhD, University Medical Center Nijmegen, Heartcenter, 540 Cardiology, PO Box 9101, Nijmegen, The Netherlands 6500 HB. E-mail f.verheugt{at}cardio.umcn.nl

Background— Despite the use of aspirin, reocclusion of the infarct-related artery occurs in {approx}30% of patients within the first year after successful fibrinolysis, with impaired clinical outcome. This study sought to assess the impact of a prolonged anticoagulation regimen as adjunctive to aspirin in the prevention of reocclusion and recurrent ischemic events after fibrinolysis for ST-elevation myocardial infarction.

Methods and Results— At coronary angiography <48 hours after fibrinolytic therapy, 308 patients receiving aspirin and intravenous heparin had a patent infarct-related artery (Thrombolysis In Myocardial Infarction [TIMI] grade 3 flow). They were randomly assigned to standard heparinization and continuation of aspirin alone or to a 3-month combination of aspirin with moderate-intensity coumarin, including continued heparinization until a target international normalized ratio (INR) of 2.0 to 3.0. Angiographic and clinical follow-up were assessed at 3 months. Median INR was 2.6 (25 to 75th percentiles 2.1 to 3.1). Reocclusion (<=TIMI grade 2 flow) was observed in 15% of patients receiving aspirin and coumarin compared with 28% in those receiving aspirin alone (relative risk [RR], 0.55; 95% CI 0.33 to 0.90; P<0.02). TIMI grade 0 to 1 flow rates were 9% and 20%, respectively (RR, 0.46; 95% CI, 0.24 to 0.89; P<0.02). Survival rates free from reinfarction and revascularization were 86% and 66%, respectively (P<0.01). Bleeding (TIMI major and minor) was infrequent: 5% versus 3% (P=NS).

Conclusions— As adjunctive to aspirin, a 3-month-regimen of moderate-intensity coumarin, including heparinization until the target INR is reached, markedly reduces reocclusion and recurrent events after successful fibrinolysis. This conceptual study provides a mechanistic rationale to further investigate the role of prolonged anticoagulation after fibrinolytic therapy.


Key Words: fibrinolysis • anticoagulants • aspirin




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