New Anti-Clotting Drug Shows Promise in Heart Patients

SUNDAY Nov. 4, 2007 -- A new anti-clotting drug might one day challenge Plavix, the current standard of therapy for people who have undergone procedures to open blocked coronary arteries, a new study suggests.

But a sizable subset of the heart patients studied -- notably those who had had a prior stroke, were elderly, or had a low body weight -- faced a significantly higher risk of potentially fatal bleeding on the new drug, known as prasugrel.

Experts said it's hard to tell whether prasugrel will replace Plavix as the first medication doctors turn to after angioplasty and stenting when trying to reduce the chances of clotting and its attendant risks, which include heart attack and stroke.

"This is not an FDA-approved drug," Dr. Dan Jones, president of the American Heart Association (AHA), said Sunday during a news conference at the AHA's annual meeting in Orlando. "Many of the questions today had to do with whether this data will be sufficient for FDA approval, and I just don't know."

The trial, funded by Daiichi Sankyo Co. Ltd. and Eli Lilly & Co., will also be published in the Nov. 15 issue of the New England Journal of Medicine.

To see if the standard therapy could be improved, researchers randomly chose 13,608 patients at 707 sites in 30 countries to receive either prasugrel (60 milligrams as a one-time "loading" dose, followed by a 10-milligram maintenance dose) or Plavix (300 milligrams initially, followed by a daily 75-milligram maintenance dose) for up to 15 months following angioplasty and stenting to open blocked arteries.

"We sought to test whether a regimen that is associated with higher degrees of inhibition of platelet aggregation, meaning it inhibits the ability of platelets to clot more effectively, would reduce events in patients undergoing percutaneous coronary intervention [PCI, also known as angioplasty]," said study senior author Dr. Elliott M. Antman, a professor of medicine at Harvard Medical School and director of the Samuel A. Levine Cardiac Unit at Brigham and Women's Hospital in Boston.

Only 9.9 percent of participants taking prasugrel died from cardiovascular causes, compared with 12.1 percent of patients taking Plavix, a 19 percent reduction. Prasugrel was also associated with a lower incidence of stent thrombosis, revascularization and heart attack.

On the other hand, the incidence of major bleeding was significantly higher with prasugrel -- 2.4 percent vs. 1.8 percent of patients on Plavix.

Still, Antman pointed out, prasugrel came out ahead.

"There were 24 fewer cardiovascular deaths with prasugrel and 16 more bleeding-related deaths so the net tally was nine fewer total deaths, which is not statistically significant," Antman said. "[But] what's important here is we believe we know where the majority of excess bleeding and most of the fatal bleeding occur -- those with prior stroke or TIA [transient ischemic attack] probably shouldn't get prasugrel, the elderly and those with a low body weight would probably benefit from a reduced maintenance dose."

A second study presented at the press conference found that a nuclear imaging technique that measures blood flow in the heart can identify which patients will benefit more from undergoing percutaneous coronary intervention than receiving medical therapy alone for blocked coronary arteries. The trial was supported by Bristol Myers-Squibb Medical Imaging and Astellas Healthcare.

Another trial found that Integrilin (eptifibatide) was as effective as ReoPro (abciximab) in restoring blood flow to the heart in patients undergoing PCI.

"Preliminary clinical events did not show any differences, therefore eptifibatide seems a valid alternative to abciximab in patients with primary PCI," said Uwe Zeymer, lead author of the study, which was conducted out of Ludwigshafen, Germany, and funded by GlaxoSmithKline.

Finally, a fourth study found that giving Integrilin for a shorter period of time after non-emergency PCI is both safe and effective.

"The brief and prolonged infusions showed no difference in terms of injury," said study author Dr. Anthony Fung, director of cardiac catheterization labs at Vancouver General Hospital, University of British Columbia, Canada. "We believe that eptifibatide can safely be abbreviated to less than two hours following successful non-emergency PCI without an increase in ischemic endpoints and perhaps with less major bleeding. This regimen is less costly because it only uses 37 percent of the standard dose and potentially can reduce nursing costs and potentially can reduce length of stay in the hospital."

Posted: November 2007


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