Evaluation of individualized clopidogrel therapy after drug-eluting stent implantation in patients with high residual platelet reactivity: design and rationale of the GRAVITAS trial.
Author(s): Price MJ, Berger PB, Angiolillo DJ, Teirstein PS, Tanguay JF, Kandzari DE, Cannon CP, Topol EJ
Affiliation(s): Division of Cardiovascular Diseases, Scripps Clinic and Scripps Advanced Clinical Trials, La Jolla, CA, USA. email@example.com
Publication date & source: 2009-05, Am Heart J., 157(5):818-24, 824.e1.
Publication type: Comparative Study; Multicenter Study; Randomized Controlled Trial
BACKGROUND: The inhibitory response to clopidogrel varies widely among individuals. Data suggest that patients with high residual platelet reactivity despite clopidogrel therapy are at greater risk for thrombotic events after percutaneous coronary intervention (PCI) with drug-eluting stents (DES). The Gauging Responsiveness with A VerifyNow assay--Impact on Thrombosis And Safety (GRAVITAS) trial is designed to evaluate whether tailored clopidogrel therapy using a point-of-care platelet function assay reduces major adverse cardiovascular events after DES implantation. STUDY DESIGN: GRAVITAS is an international, randomized, multicenter, double-blinded, placebo-controlled, clinical trial. Approximately 2,800 patients with stable angina/ischemia or non-ST-elevation acute coronary syndrome undergoing PCI with DES will be enrolled. Patients with high residual platelet reactivity on clopidogrel therapy 12 to 24 hours post-PCI will be randomized to standard maintenance clopidogrel therapy (75 mg daily) or high-dose clopidogrel therapy (additional loading dose followed by 150 mg daily) for 6 months. A random sample of patients without high residual reactivity will be followed and treated with standard clopidogrel therapy for 6 months. The primary end point is the time to first occurrence of cardiovascular death, nonfatal myocardial infarction, or definite/probable stent thrombosis. Platelet function analyses will also be performed at 30 days and 6 months. Major safety end points include GUSTO severe and moderate bleeding unrelated to coronary artery bypass surgery. CONCLUSIONS: GRAVITAS is the first large-scale clinical trial designed to examine whether adjustment of clopidogrel therapy on the basis of platelet function testing using a point-of-care assay safely improves outcomes after PCI with DES.