Low-dose warfarin and low-dose aspirin in the primary prevention of ischemic heart disease.

The thrombotic component in ischemic heart disease (IHD) is now universally recognized. It is therefore logical to consider modifying both fibrin formation and platelet function in primary (as well as secondary) prevention. The scientific case for evaluating lower-dose warfarin in primary prevention rests on the implications of the secondary prevention trials, increasing evidence of an association between the level of factor VII coagulant activity, VIIc, and the incidence of IHD, and the results of short-term lower-dose trials for the prevention of venous thrombosis and thromboembolism. The general case for considering aspirin in primary prevention is well known, but the potential value of low-dose aspirin in men at high risk needs to be established. Currently available evidence suggests that the combination of lower doses of both warfarin and aspirin in primary prevention may be effective and safe. The objective of the factorial Thrombosis Prevention Trial is to demonstrate a reduction in the incidence of IHD in men at high risk attributable to low-dose warfarin or low-dose aspirin, or both, with 1 group receiving both active treatments. The feasibility of this trial has been demonstrated. An International Normalized Ratio of about 1.5, achieved with an average daily dose of 4.6 mg warfarin, has resulted in no increase in the number of men ever reporting minor bleeding episodes, although rectal bleeding occurs more frequently in those men who do report this symptom.