Ticagrelor versus clopidogrel in ACS

Ticagrelor versus Clopidogrel in Patients with Acute Coronary Syndromes

Citation: New Eng J Med (2009-Aug-30). [Epub ahead of print].

Lars Wallentin, M.D., Ph.D., Richard C. Becker, M.D., Andrzej Budaj, M.D., Ph.D., Christopher P. Cannon, M.D., Håkan Emanuelsson, M.D., Ph.D., Claes Held, M.D., Ph.D., Jay Horrow, M.D., Steen Husted, M.D., D.Sc., Stefan James, M.D., Ph.D., Hugo Katus, M.D., Kenneth W. Mahaffey, M.D., Benjamin M. Scirica, M.D., M.P.H., Allan Skene, Ph.D., Philippe Gabriel Steg, M.D., Robert F. Storey, M.D., D.M., Robert A. Harrington, M.D., for the PLATO Investigators

ABSTRACT:

Background Ticagrelor is an oral, reversible, direct-acting inhibitor of the adenosine diphosphate receptor P2Y12 that has a more rapid onset and more pronounced platelet inhibition than clopidogrel.

Methods In this multicenter, double-blind, randomized trial, we compared ticagrelor (180-mg loading dose, 90 mg twice daily thereafter) and clopidogrel (300-to-600-mg loading dose, 75 mg daily thereafter) for the prevention of cardiovascular events in 18,624 patients admitted to the hospital with an acute coronary syndrome, with or without ST-segment elevation.

Results At 12 months, the primary end point — a composite of death from vascular causes, myocardial infarction, or stroke — had occurred in 9.8% of patients receiving ticagrelor as compared with 11.7% of those receiving clopidogrel (hazard ratio, 0.84; 95% confidence interval [CI], 0.77 to 0.92; P<0.001). Predefined hierarchical testing of secondary end points showed significant differences in the rates of other composite end points, as well as myocardial infarction alone (5.8% in the ticagrelor group vs. 6.9% in the clopidogrel group, P=0.005) and death from vascular causes (4.0% vs. 5.1%, P=0.001) but not stroke alone (1.5% vs. 1.3%, P=0.22). The rate of death from any cause was also reduced with ticagrelor (4.5%, vs. 5.9% with clopidogrel; P<0.001). No significant difference in the rates of major bleeding was found between the ticagrelor and clopidogrel groups (11.6% and 11.2%, respectively; P=0.43), but ticagrelor was associated with a higher rate of major bleeding not related to coronary-artery bypass grafting (4.5% vs. 3.8%, P=0.03), including more instances of fatal intracranial bleeding and fewer of fatal bleeding of other types.

Conclusion In patients who have an acute coronary syndrome with or without ST-segment elevation, treatment with ticagrelor as compared with clopidogrel significantly reduced the rate of death from vascular causes, myocardial infarction, or stroke without an increase in the rate of overall major bleeding but with an increase in the rate of non-procedure-related bleeding. (ClinicalTrials.gov number, NCT00391872)

Source Information From the Uppsala Clinical Research Center, Uppsala, Sweden (L.W., C.H., S.J.); Duke Clinical Research Institute, Durham, NC (R.C.B., K.W.M., R.A.H.); Grochowski Hospital, Warsaw, Poland (A.B.); Thrombolysis in Myocardial Infarction Study Group, Brigham and Women's Hospital, Boston (C.P.C., B.M.S.); AstraZeneca Research and Development, Mölndal, Sweden (H.E.), and Wilmington, DE (J.H.); Århus University Hospital, Århus, Denmark (S.H.); Universitätsklinikum Heidelberg, Heidelberg, Germany (H.K.); Worldwide Clinical Trials U.K., Nottingham, United Kingdom (A.S.); INSERM Unité 698, Assistance Publique-Hôpitaux de Paris and Université Paris 7, Paris (P.G.S.); and the University of Sheffield, Sheffield, United Kingdom (R.F.S.).

Address reprint requests to Dr. Wallentin at Uppsala Clinical Research Center, University Hospital, 75185 Uppsala, Sweden, or at lars.wallentin[at]ucr.uu.se

The abstract can be viewed at:
http://content.nejm.org/cgi/content/abstract/
361/11/1045
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