Standard- vs High-Dose Clopidogrel Based on Platelet Function Testing After Percutaneous Coronary Intervention: The GRAVITAS Randomized Trial
Do patients with high on-treatment platelet reactivity after percutaneous coronary intervention (PCI) derive clinical benefit from high-dose clopidogrel?
GRAVITAS is a randomized, double-blind, active-control trial of 2,214 patients with high on-treatment reactivity 12-24 hours after PCI with drug-eluting stents (DES) receiving high-dose clopidogrel (600 mg initial dose, 150 mg daily thereafter) or standard-dose clopidogrel (no additional loading dose, 75 mg daily) for 6 months. The primary endpoint was the 6-month incidence of death from cardiovascular causes, nonfatal myocardial infarction (MI), or stent thrombosis. The key safety endpoint was severe or moderate bleeding.
At 6 months, the primary endpoint had occurred in 2.3% receiving high-dose clopidogrel compared with 2.3% receiving standard-dose clopidogrel (hazard ratio [HR], 1.01; p = 0.97). Severe or moderate bleeding was not increased with the high-dose regimen (1.4% vs. 2.3%; HR, 0.59; p = 0.10). Compared with standard-dose clopidogrel, high-dose clopidogrel provided a 22% absolute reduction in the rate of high on-treatment reactivity at 30 days (62 vs. 40%; p < 0.001).
Among patients with high on-treatment reactivity after PCI with DES, the use of high-dose clopidogrel compared with standard-dose clopidogrel did not reduce the incidence of death from cardiovascular causes, nonfatal MI, or stent thrombosis.
Previous studies have demonstrated that high platelet reactivity, while on clopidogrel treatment, is associated with a higher rate of adverse events following revascularization procedures. Even though a higher dose of clopidogrel can reduce this platelet reactivity, it has not been shown that this will lead to a reduction in adverse vascular outcomes. Pending additional clinical trials to test different treatment strategies (i.e., prasugrel), the clinical utility of routine platelet function testing after PCI remains dubious.
Clinical Topics: Invasive Cardiovascular Angiography and Intervention
Keywords: Myocardial Infarction, Biological Markers, Platelet Function Tests, Thrombosis, Drug-Eluting Stents, Thiophenes, Blood Platelets, Piperazines, Percutaneous Coronary Intervention
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