Ticagrelor versus Clopidogrel in Patients with Acute Coronary Syndromes. Wallentin, L., Becker, R. C., Budaj, A., Cannon, C. P., Emanuelsson, H., Held, C., Horrow, J., Husted, S., James, S., Katus, H., Mahaffey, K. W., Scirica, B. M., Skene, A., Steg, P. G., Storey, R. F., & Harrington, R. A. New England Journal of Medicine, 361(11):1045–1057, September, 2009.
Ticagrelor versus Clopidogrel in Patients with Acute Coronary Syndromes [link]Paper  doi  abstract   bibtex   
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\textless0.001). 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 clopid­ ogrel; P\textless0.001). 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. 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 C­ linical Research Center, University Hospital, 75185 Uppsala, Sweden, or at lars. wallentin@ucr.uu.se. *The Study of Platelet Inhibition and Patient Outcomes (PLATO) investigators are listed in the Appendix and the Supplementary Appendix, available with the full text of this article at NEJM.org. This article (10.1056/NEJMoa0904327) was published on August 30, 2009, at NEJM. org. Conclusions 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.)
@article{wallentin_ticagrelor_2009-1,
	title = {Ticagrelor versus {Clopidogrel} in {Patients} with {Acute} {Coronary} {Syndromes}},
	volume = {361},
	issn = {0028-4793, 1533-4406},
	url = {http://www.nejm.org/doi/abs/10.1056/NEJMoa0904327},
	doi = {10.1056/NEJMoa0904327},
	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{\textbackslash}textless0.001). 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 clopid­ ogrel; P{\textbackslash}textless0.001). 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. 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 C­ linical Research Center, University Hospital, 75185 Uppsala, Sweden, or at lars. wallentin@ucr.uu.se. *The Study of Platelet Inhibition and Patient Outcomes (PLATO) investigators are listed in the Appendix and the Supplementary Appendix, available with the full text of this article at NEJM.org. This article (10.1056/NEJMoa0904327) was published on August 30, 2009, at NEJM. org. Conclusions 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.)},
	language = {en},
	number = {11},
	urldate = {2020-06-19},
	journal = {New England Journal of Medicine},
	author = {Wallentin, Lars and Becker, Richard C. and Budaj, Andrzej and Cannon, Christopher P. and Emanuelsson, Håkan and Held, Claes and Horrow, Jay and Husted, Steen and James, Stefan and Katus, Hugo and Mahaffey, Kenneth W. and Scirica, Benjamin M. and Skene, Allan and Steg, Philippe Gabriel and Storey, Robert F. and Harrington, Robert A.},
	month = sep,
	year = {2009},
	pages = {1045--1057},
	file = {Wallentin et al. - 2009 - Ticagrelor versus Clopidogrel in Patients with Acu.pdf:/Users/neil.hawkins/Zotero/storage/7S2K7PLK/Wallentin et al. - 2009 - Ticagrelor versus Clopidogrel in Patients with Acu.pdf:application/pdf;Wallentin et al. - 2009 - Ticagrelor versus Clopidogrel in Patients with Acu.pdf:/Users/neil.hawkins/Zotero/storage/W8JHHEVV/Wallentin et al. - 2009 - Ticagrelor versus Clopidogrel in Patients with Acu.pdf:application/pdf},
}
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