Variability in Responsiveness to Oral Antiplatelet Therapy

Patients who have acute coronary syndromes or are undergoing percutaneous coronary intervention receive antiplatelet therapy to reduce the risk of atherothrombotic complications. Current guidelines favor the use of aspirin in combination with clopidogrel based on the results of a number of large-scale clinical trials. Aspirin alone is a relatively weak antiplatelet agent because it inhibits only one of many paths to platelet activation. By blockade of an adjunctive signaling pathway, the addition of clopidogrel to aspirin leads to synergistic platelet inhibitory effects. Dual antiplatelet therapy reduces the number of patients who experience adverse cardiovascular outcomes by 20% over aspirin alone. Nevertheless, approximately 10% of patients experience further atherothrombotic events, even while receiving dual antiplatelet therapy. Variability in individual responsiveness, including “resistance,” has been attributed to the occurrence of these events. This article discusses variability in individual responses to oral antiplatelet therapy and its implications for clinical outcomes.