Platelets have a central role in the development of arterial thrombosis and subsequent cardiovascular events. An appreciation of this complex process has made antiplatelet therapy the cornerstone of cardiovascular disease management. Dual antiplatelet therapy with aspirin and clopidogrel has been approved for the secondary prevention of cardiovascular events and is currently part of the postpercutaneous coronary intervention treatment regimen. However, subacute stent thrombosis continues to occur in 1% to 2% of patients despite dual antiplatelet therapy. Studies have shown interindividual variations in response to clopidogrel, where a cohort of patients seems to be resistant to the antithrombotic effects of clopidogrel. Furthermore, there is an apparent link between clopidogrel resistance and clinical outcomes. Currently, there is neither a universally accepted definition of clopidogrel resistance nor an agreement on the phenomenon's mechanism. This review highlights the origins of clopidogrel resistance, the current problems that exist with its definition, and discusses the future implications and relevant challenges it poses for the clinician.
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