Evaluation of individualized clopidogrel therapy after drug-eluting stent implantation in patients with high residual platelet reactivity: design and rationale of the GRAVITAS 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.


METHODS
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.
Price
Matthew J
MJ
Division of Cardiovascular Diseases, Scripps Clinic and Scripps Advanced Clinical Trials, La Jolla, CA, USA. price.matthew@scrippshealth.org
Berger
Peter B
PB
Angiolillo
Dominick J
DJ
Teirstein
Paul S
PS
Tanguay
Jean-François
JF
Kandzari
David E
DE
Cannon
Christopher P
CP
Topol
Eric J
EJ
D000077144:Clopidogrel; D017023:Coronary Angiography; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D054855:Drug-Eluting Stents; D004562:Electrocardiography; D006083:Graft Occlusion, Vascular / Q000097:blood / Q000175:diagnosis / Q000517:prevention & control; D006801:Humans; D008297:Male; D017202:Myocardial Ischemia / Q000097:blood / Q000000981:diagnostic imaging / Q000628:therapy*; D009204:Myocardial Revascularization / Q000379:methods*; D015539:Platelet Activation / Q000187:drug effects / Q000502:physiology*; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage / Q000627:therapeutic use*; D011182:Postoperative Care / Q000379:methods*; D011446:Prospective Studies; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome
D010975:Platelet Aggregation Inhibitors; D000077144:Clopidogrel; D013988:Ticlopidine