Long-term effect of chronic oral anticoagulation with warfarin after acute myocardial infarction

Abstract

Background: Antiplatelet therapy is the principal component of the antithrombotic regimen after acute myocardial infarction. It remains unclear whether additional chronic oral anticoagulation (OAC) improves outcomes. We set out to evaluate the risk and benefit of long-term OAC after myocardial infarction.

Methods: We pooled 10 randomized clinical trials comparing warfarin-containing regimens (OAC) with or without aspirin with non-OAC regimens with or without aspirin (No OAC) for patients with recent infarction. The primary endpoint was all-cause mortality. Other endpoints included recurrent infarction, stroke, and major bleeding. We calculated the odds ratio (OR) (fixed effect, OR <1 indicates benefit for OAC) for death and other ischemic and hemorrhagic complications at the longest interval of follow-up available.

Results: Among 24,542 patients, 14,062 were assigned to OAC and 10,480 to no OAC. The patients were followed for 3-63 months, for 89,562 patient-years. Death occurred in 2424 patients (9.9%), 1279 OAC patients, and 1145 in the no OAC group, OR 0.97 (95% confidence interval [CI], 0.88-1.05), P=.43. Similarly, there was no effect on recurrent infarction. Stroke occurred in 578 patients (2.4%), 271 in the OAC group and 307 in the no OAC group, OR 0.75 (95% CI, 0.63-0.89), P=.001. There was substantially more major bleeding (OR 1.83 [95% CI, 1.50-2.23], P <.001) in the OAC group. Separate analyses, performed for patients (n=11,920) randomized to aspirin versus aspirin and OAC yielded very similar results.

Conclusion: As compared with placebo or aspirin, OAC with or without aspirin does not reduce mortality or reinfarction, reduces stroke, but is associated with significantly more major bleeding.