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Meta-analysis of several previous clinical trials, most of which were inconclusive, has recently ascertained the benefit of antiplatelet drugs in secondary prevention of myocardial infarction. This evidence has reoriented both pathogenetic and pharmacological views regarding, on the one hand, the relative role of platelets in thrombosis and in ischemic cardiovascular disease, and, on the other hand, the doubtful impact of inhibition of specific biochemical platelet targets on cardiovascular mortality. Data from meta-analysis and from more recent trials suggest that the clinical efficacy of antiplatelet drugs is likely related to their ability to interfere with thrombus formation. Although not dispelling the possibility of a concomitant antiatherosclerotic protection by antiplatelet treatment, this suggestion provides a useful guideline for the approach to primary prevention of cardiovascular mortality, in terms of treatment benefit expectancy, kind and size of population to test it, and type of drug to choose.