Testing of CYP2C19 Variants and Platelet Reactivity for Guiding Antiplatelet Treatment (in English)
Synopsis "Testing of CYP2C19 Variants and Platelet Reactivity for Guiding Antiplatelet Treatment (in English)"
Platelets play a role in the development of atherosclerotic vascular diseases such as acute and chronic coronary artery disease, ischemic cerebrovascular disease (i.e., ischemic stroke or transient ischemic attack), and peripheral arterial disease. Specifically, platelet activation and aggregation, and the interaction of platelets with blood cells and the endothelium, contribute to the pathophysiology of these diseases. Furthermore, platelets participate in thrombus formation in the setting of atrial fibrillation. Because of the importance of platelets in disease processes that often culminate in major adverse clinical events (e.g., myocardial infarction, ischemic stroke, or cardiovascular death), there is a strong rationale for the development of therapies specifically targeting platelet function for the primary and secondary prevention of cardiovascular disease. Because patient response to antiplatelet treatments is variable, there is also great interest in developing biomarkers to predict treatment response and guide treatment selection. Approximately 82 million Americans currently suffer from some form of cardiovascular disease. Randomized controlled trials have established dual antiplatelet treatment with clopidogrel and aspirin as the current standard of care for medical and interventional management of acute coronary syndromes. Dual antiplatelet treatment is also recommended for patients undergoing PCI with placement of stents (either bare metal or drug eluting). Randomized controlled trials support the use of clopidogrel in patients who have experienced acute cardiovascular events (e.g., stroke) and those with peripheral arterial disease. For patients with atrial fibrillation and contraindications to vitamin K antagonists, the ACTIVE A (Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events) trial suggested that the combination of clopidogrel and aspirin is more effective than aspirin alone for preventing thromboembolic disease. Since the approval of clopidogrel by the U.S. Food and Drug Administration (FDA) for routine clinical use, the drug has become one of the most commonly prescribed agents in the United States. However, patient response to clopidogrel-based antiplatelet therapy is variable both between patients and across multiple measurements within a patient, with some patients showing no or minimal platelet response to clopidogrel administration (often termed clopidogrel "nonresponsiveness" or "resistance"). Alternatives to standard clopidogrel treatment include higher dose clopidogrel regimens and the use of other antiplatelet agents, such as prasugrel or ticagrelor. Given the availability of alternative antiplatelet strategies and concern about adverse clinical outcomes in clopidogrel nonresponders, research has focused on methods to identify patients who are unlikely to benefit from clopidogrel-based treatment. The question of identifying the optimal antiplatelet therapy may also carry cost implications because generic clopidogrel products are now available in the United States.
