Abstract 2040: Incidence of Severe Bleeding with Long-Term Clopidogrel-Aspirin combination: comparison with Chronic Warfarin Therapy
Background Warfarin use is associated with severe bleeding (2 to 3%/yr). This is one reason physicians are reluctant to prescribe warfarin in atrial fibrillation (AF). But severe bleeding is also seen in cardiovascular patients on chronic dual antiplatelet therapy with clopidogrel-aspirin. Major clopidogrel trials have shown severe bleeding rates of nearly 2%/yr. In the randomized ACTIVE-W study in AF bleeding with clopidogrel-aspirin exceeded that of warfarin. This disturbing finding urged us to study the severe bleeding rate in the megatrials published after 1996 on either dual antiplatelet therapy alone, in those on warfarin alone, and in ACTIVE-W.
Methods and Results We analyzed the severe bleeding rate/yr with the combination clopidogrel-aspirin in the 4 major studies CURE, CREDO, MATCH and CHARISMA with 40,707 patient-years. This was also calculated for warfarin in the 3 major AF trials SPAF-III and SPORTIF III & V with 11,921 patient-years. Finally, we compared these observational results with those of the randomized ACTIVE-W trial for clopidogrel-aspirin (C): 2.4% and for warfarin (W): 2.2% (figure⇓). Dual antiplatelet therapy (mean 1.8%) seems safer than warfarin (mean 2.5%) in the observational data, but the mean patients’ age was 64 yrs in the C trials and 71 yrs in the W trials.
Conclusion Long-term combination therapy with clopidogrel-aspirin in cardiovascular patients is associated with a severe bleeding rate of 1.8%/yr, which comes close to that of chronic warfarin therapy in AF. Physicians are worried of bleeding with warfarin, but should also be aware of the enhanced risk with long-term dual antiplatelet therapy, especially when using drug-eluting stents.