The role of clopidogrel in the management of ischemic heart disease

Abstract

Placebo-controlled randomized trials have demonstrated the efficacy of clopidogrel in combination with aspirin across a broad range of clinical presentations. Recent trials have addressed several remaining issues regarding clopidogrel therapy. Three randomized trials examined the role of platelet function testing (PFT) in clopidogrel-treated patients. The results do not support the use of PFT to adjust clopidogrel dose after percutaneous coronary intervention (PCI), particularly in patients with stable angina or ischemia, in whom event rates are low irrespective of on-treatment reactivity. Doses greater than clopidogrel 150 mg daily are required to sufficiently overcome high reactivity in CYP2C19 loss-of-function (LOF) allele carriers. Clopidogrel response variability also influences the time to platelet recovery after drug discontinuation, and a proof-of-principle study supports the concept of using PFT for surgical timing. Unlike its efficacy in the setting of acute coronary syndrome (ACS) and PCI, prasugrel was not superior to clopidogrel in medically treated patients recovering from ACS. Current data do not support routine PFT to guide antiplatelet therapy in patients undergoing nonurgent PCI. The role of PFT to optimize therapy in ACS patients remains unaddressed, and further study is needed to confirm its promise in guiding surgical timing in patients who have discontinued therapy. Clopidogrel remains an important therapeutic option for patients presenting after an ACS who did not undergo initial revascularization.