Pharmacy and Therapeutics - January 2008 - (Page 51) Meeting Highlights American Heart Association, 2007 Scientific Sessions Walter Alexander Themes: Individualized Therapy and Balancing Bleeding with Thrombotic Risk This year’s meeting of the American Heart Association 2007 Scientific Sessions, which took place in Orlando, Florida, from November 4 to 7, 2007, welcomed a total of more than 26,000 attendees. Nearly 19,000 were medical professionals, and 9,000 of these were international guests. Among prominent themes in the overall program and in the topics reviewed in this article are pharmacology in the setting of myocardial infarction and acute coronary syndromes along with the promise of highly individualized therapies. TRITON–TIMI 38: Clopidogrel and Prasugrel Presenter: Elliott Antman, MD, Brigham and Women’s Hospital, Boston, Mass. Discussant: Eric Topol, MD, Scripps Health, La Jolla, Calif. Commentators: • William B. Hillegass, MD, University of Alabama, Birmingham, Ala. • Christoph Bode, MD, University of Freiburg, Germany Clinicians treating patients with blocked coronary arteries are always poised over the twin abysses of thrombosis and platelet aggregation on one side and bleeding on the other. The Trial to Assess Improvement in Therapeutic Occurrences by Optimizing Platelet Inhibition with Prasugrel (TRITON–TIMI 38) compared prasugrel (CS-747, Daiichi Sankyo/Lilly), a thienopyridine, with aspirin against the standard of care— clopidogrel (Plavix, Sanofi-Aventis) plus aspirin—in patients undergoing percutaneous coronary intervention (PCI). The hypothesis, stated lead investigator Dr. Antman, was that because prasugrel, a platelet receptor blocker, quickly produces higher and more consistent levels of inhibition of platelet aggregation (IPA), it would more successfully prevent clinical ischemic events in moderate-risk or high-risk patients with acute coronary syndrome (ACS) undergoing PCI. TRITON was presented as a late-breaking clinical trial. Among the 13,608 patients (mean age, 61 years) from 707 centers and 30 countries, 26% were undergoing primary PCI for ST-segment elevation myocardial infarction (STEMI); the rest (74%) had already undergone angiography. In the latter group, patients had moderate-risk to high-risk unstable angina or non-STEMI or STEMI within the previous 14 days; they also had ischemia or were receiving drug therapy. All patients received aspirin and were randomly assigned, in a double-blind fashion, to loading/maintenance doses of clopidogrel 30 mg/75 mg, respectively, or to loading/maintenance doses of prasugrel 60 mg/10 mg, respectively. The median duration of therapy was 12 months. The primary endpoint was The author is a freelance medical writer living in New York City. a combination of death from cardiovascular disease, MI, and stroke. Safety endpoints were TIMI major bleeding episodes and life-threatening bleeding. The clopidogrel group reached the primary endpoint more frequently (12.1% of the time) than the prasugrel group (9.3%); the hazard ratio (HR) was 0.81 (P = 0.004). The benefit was significant in both loading and maintenance dose periods. Stent thrombosis was significantly higher with clopidogrel (in 2.4% of the patients) than with prasugrel (in 1.1%) (HR, 0.48; P < 0.0001). However, bleeding (TIMI major plus non-bleeding from coronary artery bypass grafting [CABG]) was more common with prasugrel (1.8% vs. 2.4%; HR, 1.32; P = 0.03). Lifethreatening bleeding was also more common with prasugrel (1.4%) than with clopidogrel (0.9%) (HR, 1.52; P = 0.01). Bleeding risk was highest among patients with a history of stroke or transient ischemic attacks in those older than 75 years of age and weighing less than 60 kg. Dr. Antman concluded that with a 19% reduction in cardiovascular deaths, MI, and stroke, and a 52% reduction in stent thrombosis and a 32% increase in serious bleeding, the net clinical benefit significantly favored prasugrel. However, he cautioned that the regimen should be avoided in patients who have experienced a stroke. While hailing TRITON’s expansion of the antiplatelet armamentarium with prasugrel, Dr. Topol voiced concern over patient selection in TRITON, which he termed “artificial,” in that it is not typical for patients to have angiograms prior to study entry. His main concern was over the heightened (HR, 4.73) bleeding in patients undergoing bypass graft surgery. “There is already tremendous concern with clopidogrel,” he said. Asked whether prasugrel should be approved in light of the TRITON results, most experts were affirmative, albeit with reservations. Dr. Bode indicated that he would approve prasugrel only for patients who had a history of problems, for instance, those who had experienced stent thrombosis. Although in favor of approval, Dr. Hillegass said that until further studies show lower prasugrel doses to be safer, “a very good effort has to be made to educate clinicians to avoid prasugrel in prior stroke or low-weight patients.” Vol. 33 No. 1 • January 2008 • P&T® 51
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