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

Andreotti, Felicita
Testa, Luca
Biondi-Zoccai, Giuseppe G.L.
Crea, Filippo

Institute of Cardiology, Catholic University, Largo F. Vito, 00168, Rome, Italy

Received 16 June 2005; revised 4 August 2005; accepted 11 August 2005; online publish-ahead-of-print 5 September 2005

^*Corresponding author. Tel: +39 0 6 30154187; fax: +39 0 6 3055535. E-mail address: [email protected]

European Heart Journal 27(5):p 519-526, March 2006.

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.