Standard- vs High-Dose Clopidogrel Based on Platelet Function Testing After Percutaneous Coronary Intervention: The GRAVITAS Randomized Trial

Study Questions:

Do patients with high on-treatment platelet reactivity after percutaneous coronary intervention (PCI) derive clinical benefit from high-dose clopidogrel?

Methods:

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.

Results:

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).

Conclusions:

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.

Perspective:

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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