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| |  Ticagrelor Superior to Clopidogrel in Reducing Vascular Events, Death in Patients With Acute Coronary Syndrome: Presented at ESC(CARD) By Walter Alexander BARCELONA, Spain -- August 31, 2009 -- In patients with acute coronary syndrome (ACS) with or without ST-segment elevation, ticagrelor significantly reduces rates of death from vascular causes, myocardial infarction (MI), or stroke compared with clopidogrel without increasing overall major bleeding, researchers stated here at the 2009 Congress of the European Society of Cardiology (ESC(CARD)). However, non-procedure-related bleeding, including fatal intracranial bleeding, was increased, however. In a Hot Line presentation on August 30, Lars C. Wallentin, MD, Uppsala Clinical Research Center, Uppsala, Sweden, noted that current practice guidelines recommend dual antiplatelet therapy with aspirin and clopidogrel for ACS. Clopidogrel’s efficacy, however, can be diminished by slow or variable transformation of the prodrug to the active metabolite, by weak or variable platelet inhibition, increased bleeding, and in some patients with poor response, higher risks of stent thrombosis and MI. While the newer thienopyridine prodrug prasugrel inhibits platelets more strongly than clopidogrel, leading to lower MI and stent thrombosis risks, it is associated with higher major bleeding rates in ACS patients undergoing percutaneous coronary interventions. Compared with clopidogrel, it also has a faster onset of action. The multicentre, double-blind, randomised Platelet Inhibition and Patient Outcomes (PLATO) trial compared ticagrelor and clopidogrel in 18,624 patients who were admitted to the hospital with ACS (with or without ST-segment elevation). Patients received ticagrelor (n = 9,333) in a 180-mg loading dose with 90 mg twice daily thereafter or clopidogrel (n = 9,291) in a 300 to 600-mg loading dose with 75 mg daily thereafter. Treatment was scheduled to continue for 12 months. The primary endpoint was a composite of death from vascular causes, MI, or stroke. Death from vascular causes included death from cardiovascular or cerebrovascular causes and any death without another known cause. At 12 months, the primary composite endpoint was reported significantly less often in the ticagrelor group than in the clopidogrel group (9.8% vs 11.7%; hazard ratio, 0.84; 95% confidence interval, 0.77-0.92; P < .001). This treatment effect appeared within 30 days and was maintained throughout the study period. Secondary endpoints favouring ticagrelor included MI (5.8% ticagrelor vs 6.9% clopidogrel; P = .005), death from vascular causes (4.0% ticagrelor vs 5.1% clopidogrel; P = .001), and death from any cause (4.5% ticagrelor vs 5.0% clopidogrel; P < .001). Major bleeding was similar between treatment groups (11.6% ticagrelor vs 11.2% clopidogrel; P = .43). Major bleeding not related to coronary artery bypass grafting was higher with ticagrelor (4.5% vs 3.8% clopidogrel; P = .03), with more fatal intracranial bleeding but less bleeding of other types. [Presentation title: Comparison of Ticagrelor, the First Reversible Oral P2Y12 Receptor Antagonist, With Clopidogrel in Patients With Acute Coronary Syndromes: Results of the Platelet Inhibition and Patient Outcomes (PLATO) Trial]
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