Patients with thrombolysis in myocardial infarction (TIMI) 3 flow c;48 hours after fibrinolysis for ST-elevation myocardial infarction were randomized to aspirin plus coumarin, with prolonged heparinization until the target international normalized ratio (2-3) was reached, or aspirin with standard heparinization. Three-month follow-up angiography (reocclusion rates 15 % vs 28 % ) and long-term clinical follow-up (median 7.3 years, interquartile range 5.9-8.6 years) were performed.
Patients randomized to adjunctive anticoagulation (n = 123) received coumarin for a median of 280 days (113-387 days). Survival was 94 % versus 88 % in patients on aspirin alone (n = 128, P = .12). Infarct-free survival was 86 % versus 71 % (P = .01). Thrombolysis in myocardial infarction bleeding was 4 % in both groups. Patients with reocclusion had impaired survival: 80 % versus 94 % (P c; .01). In a multivariable model without reocclusion, combination therapy independently predicted survival (hazard ratio [HR] 0.36, 95 % confidence interval [CI] 0.13-1.00) and infarct-free survival (HR 0.51, 95 % CI 0.28-0.95). When adjusted for reocclusion, combination therapy did not predict outcome. Reocclusion independently predicted death (HR 2.56, 95 % CI 1.02-6.43) and reinfarction.
Moderate-intensity oral anticoagulation added to aspirin improved 8-year clinical outcome after successful fibrinolysis. The beneficial effect was largely attributed to a reduction in reocclusion, which independently predicted death and reinfarction. This study provides a mechanistic rationale for prolonged adjunctive anticoagulation after fibrinolysis.