High-Dose Clopidogrel Does Not Reduce Mortality Incidence
No mortality reduction over standard dose after percutaneous coronary intervention
WEDNESDAY, March 16 (HealthDay News) -- A higher dose of clopidogrel does not reduce the incidence of death from cardiovascular causes, nonfatal myocardial infarction (MI), or stent thrombosis in patients with high platelet reactivity after percutaneous coronary intervention (PCI) with drug eluting stents, according to a study published in the March 16 issue of the Journal of the American Medical Association.
Matthew J. Price, M.D., from the Scripps Clinic in La Jolla, Calif., and colleagues compared the effect of high-dose versus standard-dose clopidogrel in participants of the Gauging Responsiveness with A VerifyNow assay -- Impact on Thrombosis And Safety (GRAVITAS) trial with high platelet reactivity 12 to 24 hours after PCI with drug-eluting stents. A total of 1,109 participants received high-dose clopidogrel (initial dose 600 mg, then 150 mg daily) and 1,105 received standard-dose clopidogrel (75 mg daily) for six months. The pharmacodynamic end point was a persistently high rate of on-treatment reactivity at 30 days, and the safety end point was severe or moderate bleeding. Primary study end points were incidence of death from cardiovascular causes, nonfatal MI, or stent thrombosis.
The investigators found that 2.3 percent of the participants in both clopidogrel groups died from cardiovascular causes, had a nonfatal MI, or had stent thrombosis (hazard ratio [HR], 1.01). There was a 22 percent absolute reduction in the rate of high on-treatment reactivity at 30 days and no increase in bleeding (HR, 0.59) in the high-dose group compared with the standard dose.
"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," the authors write.
Several of the study authors disclosed financial ties with the pharmaceutical and medical device industries.