Combined use of aspirin and warfarin in primary prevention of ischemic heart disease in men at high risk.

The combination of aspirin and warfarin is likely to be more effective than either agent alone in the prevention of ischemic heart disease (IHD), but its practical value also crucially depends on a low incidence of serious bleeding. The occurrence of bleeding of different degrees of severity is being established in the Thrombosis Prevention Trial of primary prevention in men aged 45-69 years at increased risk of IHD, in which 75 mg aspirin and warfarin dosed to an international normalized ratio of 1.5 are used in a factorial design. The annual risk of serious bleeding, i.e., requiring transfusion or surgery, may be about 1 in 500 for those on active treatment, whether this consists of both aspirin and warfarin or either alone. Less serious degrees of bleeding are significantly increased by the combination of aspirin and warfarin compared with either alone and by either alone compared with placebo. The risk of serious bleeding is probably acceptable if low dosages are used.