Drug Topics - December 10, 2007 - (Page HSE2)

2 HSE DRUG TOPICS DECEMBER 10, 2007 www.drugtopics.com > > > Clinical Practice New trials may cut clopidogrel use Fred Gebhart trio of late-breaking clinical trials could change standard drug treatment for patients undergoing percutaneous coronary intervention, or PCI. Dual antiplatelet therapy, aspirin plus a thienopyridine, is standard to prevent thrombotic complications in patients with acute coronary syndrome (ACS) and those undergoing PCI. A phase III trial, TRITON-TIMI 38, could open the door for a new thienopyridine agent—prasugrel (Daiichi Sankyo/Lilly)—to compete with clopidogrel (Plavix, sanofiaventis/Bristol-Meyers Squibb) to reduce complications in patients who have undergone PCI. And two trials support institutions that are replacing abciximab (ReoPro, Centocor/Lilly) with eptifibatide (Integrilin, Schering-Plough) to maintain coronary perfusion following PCI. The three trials were discussed at the American Heart Association’s annual Scientific Sessions in Orlando, Fla., last month. A prior stroke or transient ischemic attack (TIA) and the frail elderly (over 75, weighing <60 kg), he added. “This is an approvable drug. But I would not give it to a patient with a prior stroke or TIA. Fully 80% of the individuals in this trial had a net clinical benefit from prasugrel.” Mixed reaction Reaction to prasugrel was not all positive. Writing in a New England Journal of Medicine editorial, Deepak Bhatt, M.D., associate director, Cleveland Clinic Cardiovascular Coordinating Center, warned that the risk of major bleeding in elderly patients with multiple comorbidities may be even higher in real-world situations than in the trial. There was less reaction to studies that supported the use of eptifibatide over abciximab for coronary reperfusion following PCI. In Europe, the EVA-AMI study found that a double bolus of eptifibatide is as effective as abciximab in reducing ischemic complications following PCI. Both drugs are glycoprotein IIb/IIIa inhibitors, which reduce clot formation by blocking platelet aggregation. The comparison of the two agents randomized 430 patients following acute ST elevation myocardial infarction (STEMI) and PCI to open blocked coronary arteries. There was no difference between the two drugs in clinical efficacy, said lead author of the study Uwe Zeymer, M.D., based in Ludwigshafen, Germany. But there is a significant difference in cost: $1,700 per patient for abciximab versus $400 for eptifibatide, said Anthony Fung, M.D., director of cardiac catheterization, University of British Columbia (UBC) Vancouver General Hospital. That difference prompted UBC to switch to eptifibatide based on observational studies. Those studies also suggested that a shorter course of eptifibatide could be as effective as the standard double bolus plus 18-hour infusion. The BRIEF-PCI study randomized 624 patients who had nonemergency PCI to either standard treatment or a double bolus plus less than two hours of infusion. The 18hour and under-two-hour infusions produced the same rates of ischemic myocardial injury following PCI, as well as death, post-PCI MI, and urgent target vessel revascularization within 30 days. The shorter infusion reduced major bleeding from 4.2% of patients to less than 1%. “Clinicians tend to favor eptifibatide just on cost,” Fung said. “This shows that infusion can safely be reduced to less than two hours. That reduces drug use to 37% of the standard dosing, which probably accounts for the lower incidence of major bleeding.” DT Head-to-head A head-to-head trial of prasugrel and clopidogrel concluded that prasugrel is more potent, works more quickly, and has more consistent antiplatelet activity. “There was an early and sustained benefit from prasugrel that started with the loading dose [LD],” said Elliott Antman, M.D., professor of medicine at Harvard Medical School. “The benefits the higher degree of inhibition of platelet aggregation achieved with prasugrel in TRITONElliott Antman (l.), Uwe Zeymer (c.), and TIMI 38 represent Anthony Fung presented new cardiovascular findings at the recent American Heart the latest advance in Association meeting. antiplatelet therapy.” The international trial enrolled 13,608 patients at 707 sites, Antman said. All of the patients had moderate- to high-risk ACS and were scheduled to undergo PCI. Patients were randomized to receive either prasugrel (60 mg LD plus 10 mg daily maintenance) or clopidogrel (300 mg LD plus 75 mg daily maintenance) following PCI. Treatment continued for up to 15 months after PCI. Prasugrel significantly reduced myocardial infarction (MI), urgent target vessel revascularization, and stent thrombosis compared with clopidogrel, Antman reported. The downside of the new drug is increased bleeding. The risk of major bleeding was concentrated in patients with Photos: Fred Gebhart http://www.drugtopics.com

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Drug Topics - December 10, 2007 Latebreakers Latebreakers in Depth Letters Health-System Edition - Cover Story Clinical Practice Professional Practice Special Report Technology Community Practice Unraveling Medicare 150 Years of American Pharmacy Rx Care In the Pipeline Cover Story: Fair or foul? Self-Care Chains and Business Government and Law Continuing Education: Natural Medicines for Bone Health New Products Advertisers Index Classified Viewpoint

Drug Topics - December 10, 2007

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