Increasing the dose of clopidogrel, an anti-platelet drug for 6 months depending on the patient's level of platelet reactivity, the drug did not result in lower rate of non-fatal heart attack, stent thrombosis (clot) and cardiovascular death.
Current guidelines recommend treating patients undergoing percutaneous coronary intervention (PCI; procedure such as balloon angioplasty used to open narrowed coronary arteries) and drug-eluting stent implantation with a combination of aspirin and P2Y12 (compound found on the surface of blood platelet cells and an important regulator in blood clotting) antagonist for at least 1 year. But several studies have suggested that patients with high platelet reactivity during treatment with clopidogrel are at an increased risk of cardiovascular events after PCI. A treatment strategy for this issue has not been well defined, according to background information in the article. The study was published in March 16 issue of JAMA.These patients underwent a procedure known as balloon angioplasty and received a drug-releasing coronary stent.
Matthew J. Price, M.D., of Scripps Translational Science Institute, La Jolla, Calif., and colleagues conducted the Gauging Responsiveness with A VerifyNow assay-Impact on Thrombosis And Safety (GRAVITAS) trial to determine whether high-dose clopidogrel is superior to standard-dose therapy for the prevention of cardiovascular events after PCI in patients with high on-treatment reactivity. The randomized trial included 2,214 patients with high on-treatment reactivity (measured 12 to 24 hours after PCI) with drug-eluting stents at 83 centers in North America between July 2008 and April 2010. Patients received high-dose clopidogrel (600-mg initial dose, 150 mg daily thereafter) or standard-dose clopidogrel (75 mg daily) for 6 months. The primary outcome measured was the 6-month incidence of death from cardiovascular causes, nonfatal heart attack, or stent thrombosis. Safety measurements included severe or moderate bleeding.
The reduction in on-treatment reactivity at 30 days and at 6 months after randomization was significantly greater with high-dose than with standard-dose clopidogrel. High-dose clopidogrel was associated with an absolute 22 percent lower rate of high on-treatment reactivity compared with standard-dose clopidogrel at 30 days and 6 months (40 percent vs. 62 percent; and 36 percent vs. 60 percent, respectively).
Severe or moderate bleeding was not increased with the high-dose regimen.
"In conclusion, high-dose clopidogrel for 6 months in patients with high on-treatment platelet reactivity 12 to 24 hours after PCI with drug-eluting stents did not reduce the rate of death from cardiovascular causes, nonfatal myocardial infarction, or stent thrombosis compared with standard-dose clopidogrel. 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. Alternative treatment strategies incorporating platelet function testing merit further investigation," the authors write.