Aspirin plus warfarin compared to aspirin alone after acute coronary syndromes: an updated and comprehensive meta-analysis of 25 307 patients

Aims In patients recovering from acute coronary syndromes (ACS) the role of oral anticoagulation (and its intensity) in addition to aspirin remains controversial. We conducted a specific meta-analysis of randomized trials comparing aspirin plus warfarin (A+W) with aspirin alone in such patients. Methods and results MEDLINE and Cochrane databases yielded 14 (of 148 potentially relevant) articles enrolling 25 307 patients. Follow-up ranged from 3 months to 5 years. Irrespective of International normalized ratio (INR), A+W did not significantly affect the risk of major adverse events (MAE: all cause death, non-fatal myocardial infarction, and non-fatal thrombo-embolic stroke) when compared with aspirin alone [OR 0.96 (0.90-1.03), P=0.30], but increased the risk of major bleeds (MB): OR 1.77 (1.47-2.13), P < 0.00001. However, in studies with INR of 2-3, A+W was associated with a significant reduction of MAE [OR 0.73 (0.63-0.84), P < 0.0001, number needed to treat to avoid one MAE=33], albeit at an increased risk of MB [OR 2.32 (1.63-3.29), P < 0.00001; number needed to harm by causing one MB=100]. In both analyses, intracranial bleeding was not significantly increased by A+W when compared with aspirin alone. Conclusion For patients recovering from ACS, a combined strategy of A+W at INR values of 2-3 doubles the risk of MB, but is nonetheless superior to aspirin alone in preventing MAE. Whether this combined regimen is also superior to a 'double' anti-platelet strategy or to newer evolving treatments warrants further investigation.