High-dose clopidogrel does not reduce mortality after PCI

The use of high-dose clopidogrel compared with use of standard-dose clopidogrel does not reduce the incidence of death from cardiovascular causes, nonfatal myocardial infarction (MI), or stent thrombosis among patients with high on-treatment reactivity after percutaneous coronary intervention (PCI) with drug-eluting stents, according to a recent multicenter study published in the March 16, 2011, issue of the Journal of the American Medical Association.

Researchers compared high-dose clopidogrel (600-mg initial dose, 150-mg thereafter) with standard-dose clopidogrel (no additional loading dose, 75-mg daily) for 6 months in 2,214 patients participating in the Gauging Responsiveness with A VerifyNow assay -Impact on Thrombosis And Safety (GRAVITAS) study. The patients had high on-treatment reactivity 12 to 24 hours after PCI with drug-eluting stents.

At 6 months, 25 of 1,109 patients (2.3%) receiving high-dose clopidogrel compared with 25 of 1,105 patients (2.3%) receiving standard-dose clopidogrel died from cardiovascular causes, had a nonfatal MI, or had stent thrombosis. High-dose clopidogrel provided a 22% absolute reduction in the rate of high on-treatment reactivity at 30 days compared with standard-dose treatment. In addition, severe or moderate bleeding was not associated with the high-dose regimen.

"The results of GRAVITAS do not support a uniform treatment strategy of high-dose clopidogrel in patients with high on-treatment reactivity identified by a single platelet function test after PCI," concluded the researchers.