Aspirin plus warfarin therapy: Better alternatives available

The study by Andreotti and Testa from Rome, Italy, was a retrospective literature review and meta-analysis of treatment with aspirin and warfarin (Coumadin) in survivors of acute coronary syndromes. Although the number of patients studied is impressive—25,307—it is difficult to decide how to use the information.

First and foremost, because we now have additional antiplatelet drugs available and the most common regimen for post—acute coronary syndrome is double antiplatelet therapy, I doubt whether this study will convince many physicians to switch to a regimen of aspirin and warfarin, especially because clopidogrel (Plavix) is so well tolerated. In addition, the increased risk of major bleeding is also a deterrent to using this regimen, especially because intracranial bleeding occurred in this group. Finally, the “workload” for the patient and treating physician for using warfarin, with dose adjustments and recurrent blood testing, makes it even more unlikely that this would be a choice of treatment unless there was striking evidence of benefit. This brings me to what this study actually did show.

The meta-analysis included 14 studies worldwide, in which unstable angina and non—ST-segment elevation myocardial infarction patients were treated within 1 to 8 weeks after onset and followed for from 3 months to 5 years. Different studies used different targeted international normalized ratio (INR) ranges. In the overall analysis, there was no cardiac benefit to aspirin plus warfarin, but there was an increase in major bleeding. The only benefit was that the combination regimen reduced the overall risk of nonfatal thromboembolic stroke—1.6% for combination treatment vs 2.1% for aspirin alone.

In the restricted analysis of only those studies that used an INR of 2 to 3, there was a reduction in major adverse events, from 12.3% to 9.4% for aspirin alone. However, all-cause mortality was the same for both groups.

To summarize, I think the data were excessively stretched to come up with some benefit for combination therapy with aspirin and warfarin, but not convincingly enough to persuade me that further studies for this regimen should be funded, especially in light of the good alternatives we have available to us. In addition, in the United States, most patients with this syndrome are treated with coronary intervention and then with double antiplatelet therapy. In this drug-eluting stent era, double antiplatelet therapy is frequently given for an indefinite period because of the fear of late stent thrombosis.