Sunday, November 4, 2007

AHA - 2007: TRITON - TIMI 38

New antiplatelet therapy improves outcomes

American Heart Association Scientific Sessions Late-Breaking News:

ORLANDO, Nov. 4 – The antiplatelet drug prasugrel offered greater benefit than current, standard therapy for patients who have undergone percutaneous coronary intervention (PCI), according to a late-breaking clinical trial presented at the American Heart Association’s Scientific Sessions 2007.

Dual antiplatelet therapy with aspirin plus a prescription antiplatelet drug is standard treatment for helping reduce complications such as heart attacks or clotting in stents in patients with acute coronary syndromes (ACS) who have undergone PCI to open blocked coronary arteries.

TRITON - TIMI 38, a large, international, double-blind phase 3 trial, compared single dosage regimens of prasugrel, a novel antiplatelet drug, and clopidogrel, a commonly used prescription antiplatelet. Both medications are in a class of drugs called thienopyridines.

At these doses, “Prasugrel was been shown to be more potent, work more quickly and have more consistent antiplatelet effects than standard, approved doses of clopidogrel,” said Elliott M. Antman, M.D., professor of medicine at Harvard Medical School and director of the Samuel A. Levine Cardiac Unit at Brigham and Women’s Hospital in Boston, Mass.

TRITON - TIMI 38 enrolled 13,608 patients with moderate to high-risk ACS who were scheduled to undergo PCI. Participants were randomized at 707 sites in 30 countries. Patients were given either prasugrel (60 mg as a one-time “loading” dose, followed by a daily 10 mg maintenance dose) or clopidogrel (300 mg loading dose and a daily 75 mg maintenance dose) for up to 15 months following PCI.

The primary efficacy endpoint (death from cardiovascular causes, heart attack or stoke) was significantly lower on prasugrel (12.1 percent of patients randomized to clopidogrel and 9.9 percent of patients randomized to prasugrel (HR 0.81[0.73-0.90], P=0.0004)), meeting the primary hypothesis of superiority. This dose of prasugrel was also associated with a significantly lower incidence of stent thrombosis (HR 0.48[0.36-0.64], P<0.0001), urgent target vessel revascularization (HR 0.66 [0.54-.081], P<0.0001) and heart attacks (HR 0.76 [0.67-.085], P<0.0001). While major bleeding was also significantly higher with prasugrel (2.4 percent of patients versus 1.8 percent of patients randomized to clopidogrel (HR 1.32 [1.03-1.68], P=0.03), the balance of efficacy and safety, net clinical benefit (all cause mortality, nonfatal MI, nonfatal stroke, or nonfatal major bleed), favored prasugrel (HR 0.87 [0.79-0.95], P=0.004).

“Although clopidogrel is a highly effective antiplatelet drug, many patients who receive it still have serious ischemic events despite reliably taking the drug,” said Antman. “The benefits of the higher degrees of inhibition of platelet aggregation achieved with the doses of prasugrel that we tested in TRITON-TIMI 38 represent the latest advance in antiplatelet therapy for patients with an acute coronary syndrome.”

Antman said there were some patients who did not do as well with this dosage of prasugrel, such as those who had a history of prior stroke, were elderly and had a low body weight. Potential modifications of the maintenance dose will be guided by ongoing analyses of a pharmacokinetic substudy in TRITON-TIMI 38.

Support for this study was provided by Daiichi Sankyo Co. Ltd and Eli Lilly & Co.

Statements and conclusions of study authors that are presented at American Heart Association scientific meetings are solely those of the study authors and do not necessarily reflect association policy or position. The American Heart Association makes no representation or warranty as to their accuracy or reliability.

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