GRAVITAS trial results show that high-dose clopidogrel does not reduce the incidence of death, heart attack, or blood clots in high-risk patients.
Study results show that giving patients double the dose of the commonly used blood-thinner clopidogrel does not reduce the incidence of death, heart attack, or blood clots in high-risk patients implanted with drug-coated stents.
Earlier studies have shown that clopidogrel works well in some patients who have undergone percutaneous coronary intervention (PCI) to implant a stent to open a blocked artery. But some patients have high residual platelet reactivity and are still prone to clotting despite taking the drug.
Presenting data from the Gauging Responsiveness With A VerifyNow Assay — Impact on Thrombosis and Safety (GRAVITAS) trial at the American Heart Association Scientific Sessions 2010, lead investigator Matthew J. Price, MD, said that “patients with high residual platelet reactivity have a higher risk of major cardiovascular events after procedures to implant stents.”
The GRAVITAS trial was designed to determine if high-dose clopidogrel reduces cardiovascular events in patients with high residual platelet reactivity. In GRAVITAS, researchers gave a loading dose followed by a high maintenance dose of clopidogrel.
“The high dose of clopidogrel doesn’t appear to improve outcomes, so alternative treatment strategies should be tested,” said Price, director of the Cardiac Catheterization Laboratory at the Scripps Clinic, and assistant professor at the Scripps Translational Science Institute in La Jolla, CA.
Price expects this new data to change the way cardiologists treat these patients. He said that “Many physicians have been using a high dose of clopidogrel as a default strategy in patients who are nonresponsive to the drug. We have shown that this strategy is probably ineffective.”
The six-month trial, involving about 80 centers throughout the United States and Canada, randomized 2,214 patients who had a specific platelet function test after the PCI procedure that revealed they had high residual platelet activity. Those patients were randomly assigned to either receive a high dose of clopidogrel 150 mg daily, or the standard daily dose of 75 mg, with an inactive placebo.
The composite end point (the rate of death from cardiovascular causes, of heart attacks, and of blood clots in stents) at six months in patients randomized to high-dose clopidogrel was 2.3%, identical to that in patients randomized to standard dose clopidogrel. Further analysis of the GRAVITAS data is expected in early 2011.
Price said this trial serves as a model for future research into personalized therapy, which may one day reduce the need for extremely large clinical trials that include many thousands of patients. “If we can identify certain high-risk patients based upon their individual response to therapy, instead of mega trials, we can potentially find effective therapy using a much smaller trial size,” he said.
Although the proposed regimen failed to reduce the risk of dangerous events, the data showed that it didn’t cause additional bleeding, so the patients weren’t harmed at the higher dose. “GRAVITAS is addressing the question of whether personalized, selective anti-platelet therapy may have substantial benefit when treating the highest risk patients,” Price said. “Traditional trials seek the best treatment for the average patient. GRAVITAS is using a personalized approach, which seeks to identify the best treatment for a particular individual. This is a paradigm-shifting approach for evidence-based medicine.”