High-dose clopidogrel no better than standard dose in post-PCI patients at high risk of clots
Richard Philip

Compared to a standard dose of clopidogrel, a higher dose of the anti-clotting agent did not reduce mortality, heart attack or the formation of in-stent blood clots in patients with high platelet reactivity who had undergone percutaneous coronary intervention (PCI) with drug-eluting stents, according to clinical trial findings.

The Gauging Responsiveness With A VerifyNow Assay – Impact on Thrombosis and Safety (GRAVITAS) trial tested whether high-dose clopidogrel (150 mg per day) was superior to standard dose clopidogrel (75 mg per day) in post-PCI patients with high residual platelet reactivity according to a point-of-care platelet function test.

Although clopidogrel works well in some patients who have undergone PCI, the agent has not been as effective in patients with high residual platelet reactivity who have an increased propensity for developing blood clots, even after taking anti-clotting medication.

“Those with high residual platelet reactivity have a higher risk of major cardiovascular events after procedures to implant stents,” said Dr. Matthew J. Price, the study’s lead investigator.

“The high dose of clopidogrel doesn’t appear to improve outcomes, so alternative treatment strategies should be tested,” said Price, who is director of the Cardiac Catheterization Laboratory at the Scripps Clinic and assistant professor at the Scripps Translational Science Institute, both located in San Diego, California, US.

The results, Price noted, are expected to change the way cardiologists treat these high-risk patients. “Many physicians have been using a high dose of clopidogrel as a default strategy in patients who are nonresponsive to the drug,” he said. “We show that this strategy is probably ineffective.”

In the trial, 2,214 patients found to have high residual platelet activity according to a specific platelet function test (the VerifyNow® P2Y12 test developed by the company Accumetrics based in San Diego, California, US) conducted 12 to 24 hours after PCI, were randomly assigned to either a high or a standard daily dose of clopidogrel for a period of 6 months.

The primary efficacy endpoint was a composite of death from cardiovascular causes, heart attacks and stent thrombosis at 6 months of follow up.

Patients who received higher doses had identical event rates as those who received standard doses – 2.3 percent in each arm. The trial also showed that high-dose clopidogrel in patients with high platelet reactivity did not lead to an excess of bleeding events.

“It is important to apply our results to the population that we studied. And in the end, although [the trial] was open to both stable and unstable coronary artery disease [patients] the majority of patients – 84 percent – had stable coronary artery disease or low-risk unstable angina. So [the results] need to be applied to that cohort of patients,” concluded Price.