BACKGROUND: Aspirin is widely used as an antiplatelet drug in patients with coronary heart disease. Despite documented clinical benefit, many patients on aspirin still experience severe cardiovascular events. Several laboratory reports have shown lack of platelet inhibition in 5-40% of aspirin-treated patients, and the term aspirin resistance has been introduced. The clinical relevance of these laboratory findings is, however, still unknown. New antiplatelet drugs have been developed, and the adenosin diphosphate (ADP) receptor inhibitor clopidogrel has at least the same efficacy as aspirin with an acceptable safety profile. Laboratory methods for determination of platelet reactivity and treatment efficacy have been complicated and time consuming. New methodologies, like the PFA-100 system, have made such analyses more suitable for clinical use. DESIGN: In the ASCET study, 1000 patients with documented coronary heart disease will be randomized to either continued treatment with aspirin 160 mg/d or change to clopidogrel 75 mg/d after initial determination of their platelet reactivity while on aspirin treatment. Clinical endpoints will be recorded for at least 2 years and related to the initial aspirin response.