Higher Plavix Dose Won't Boost Outcomes After Stent Placement: Study
TUESDAY Nov. 16, 2010 -- Higher doses of the blood-thinner Plavix were no better at preventing heart attacks, blood clots or death than the standard lower dose in patients who had received artery-opening stents, new research shows.
The higher dose -- double the usual amount -- was tested in patients with "high platelet reactivity," meaning they failed to respond to the drug at lower doses.
Plavix (clopidogrel) helps prevent clots from forming in patients who have low platelet reactivity and who have had stents inserted to prop open blocked arteries.
But the new study "doesn't support" physicians using the higher, 150-milligram dose of Plavix after stenting, according to study lead author Dr. Matthew Price, who presented the findings Tuesday at the annual meeting of the American Heart Association in Chicago.
So, the study leaves an important question unanswered: How to treat heart patients who don't respond well to Plavix?
"It remains uncertain to some extent," said Dr. Abhiram Prasad, an interventional cardiologist with the Mayo Clinic in Rochester, Minn. "It's an important study to have done but the key issues are that a significant proportion of the patients remained with high platelet reactivity even after being on the higher dose."
Previous, smaller studies had indicated that Plavix might have more of an effect if the dose was doubled.
"Platelet reactivity varies widely," noted Price, director of the Cardiac Catheterization Laboratory at the Scripps Clinic in La Jolla, Calif. He explained that numerous studies have shown that a high reactivity level is associated with poorer outcomes after angioplasty and/or stenting. But until now, a steep rise in the dose of Plavix "has not been tested in a large randomized clinical trial," he said.
For this trial, investigators tested a large group of patients for platelet reactivity after they had undergone angioplasty to place a drug-eluting stent. Drug-eluting stents emit medicines that help ward off vessel re-closure.
Over 2,200 patients with high platelet reactivity were then randomized to receive 150 milligrams a day of Plavix or the standard 75-milligram dose.
After six months, 2.3 percent of those taking either the higher or the lower dose suffered heart attacks, experienced blood clots in their stents, or died, the researchers report.
Those taking the higher dose of the blood-thinner didn't have any worse bleeding than those taking the standard dose, indicating that the higher dose of Plavix in this group of patients wasn't any less safe.
The study was sponsored by Accumetrics, which makes VerifyNow, a test used to measure platelet function. The makers of Plavix, Sanofi-Aventis and Bristol-Myers Squibb provided the drug, and lead investigator Price also disclosed ties with pharmaceutical companies.
"The trial does not support a treatment strategy of high dose clopidogrel in . . . patients with high-risk reactivity identified by a single platelet test," Price said.
Still, Prasad said that higher risk patient populations may need to be studied before drawing any firm conclusions about dosing. "Or maybe we need a more potent drug," he said.
For more on stents, visit the U.S. National Heart, Lung, and Blood Institute.
Posted: November 2010