Comparative Efficacy and Safety of Oral P2Y12Inhibitors in Acute Coronary Syndrome: Network Meta-Analysis of 52 816 Patients from 12 Randomized Trials

E.P. Navarese, S.U. Khan, M. Kołodziejczak, J. Kubica, S. Buccheri, C.P. Cannon, P.A. Gurbel, S. De Servi, A. Budaj, A. Bartorelli, D. Trabattoni, E.M. Ohman, L. Wallentin, M.T. Roe, S. James

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Background: New randomized, controlled trials have become available on oral P2Y12inhibitors in acute coronary syndrome. We aimed to evaluate current evidence comparing the efficacy and safety profile of prasugrel, ticagrelor, and clopidogrel in acute coronary syndrome by a meta-analysis of randomized controlled trials. Methods: We performed a network meta-analysis and direct pairwise comparison analysis of efficacy and safety outcomes from 12 randomized controlled trials including a total of 52 816 patients with acute coronary syndrome. Results: In comparison with clopidogrel, ticagrelor significantly reduced cardiovascular mortality (hazard ratio [HR], 0.82 [95% CI, 0.72-0.92]) and all-cause mortality (HR, 0.83 [95% CI, 0.75-0.92]), whereas there was no statistically significant mortality reduction with prasugrel (HR, 0.90 [95% CI, 0.80-1.01] and HR, 0.92 [95% CI, 0.84-1.02], respectively). In comparison with each other, there were no significant differences in mortality (HR prasugrel versus ticagrelor, 1.10 [95% CI, 0.94-1.29] and 1.12 [95% CI, 0.98-1.28]). In comparison with clopidogrel, prasugrel reduced myocardial infarction (HR, 0.81 [95% CI, 0.67-0.98]), whereas ticagrelor showed no risk reduction (HR, 0.97 [95% CI, 0.78-1.22]). Differences between prasugrel and ticagrelor were not statistically significant. Stent thrombosis risk was significantly reduced by both ticagrelor and prasugrel versus clopidogrel (28%-50% range of reduction). In comparison with clopidogrel, both prasugrel (HR, 1.26 [95% CI, 1.01-1.56]) and ticagrelor (HR, 1.27 [95% CI, 1.04-1.55]) significantly increased major bleeding. There were no significant differences between prasugrel and ticagrelor for all outcomes explored. Conclusions: Prasugrel and ticagrelor reduced ischemic events and increased bleeding in comparison with clopidogrel. A significant mortality reduction was observed with ticagrelor only. There was no efficacy and safety difference between prasugrel and ticagrelor. Registration: URL:; Unique identifier: CRD42019155648. © 2020 Lippincott Williams and Wilkins. All rights reserved.
Original languageEnglish
Pages (from-to)150-160
Number of pages11
Issue number2
Publication statusPublished - 2020


  • acute coronary syndrome
  • meta-analysis
  • P2Y12protein, human
  • clopidogrel
  • prasugrel
  • purinergic P2Y receptor antagonist
  • purinergic P2Y12 receptor
  • ticagrelor
  • all cause mortality
  • Article
  • bleeding
  • brain hemorrhage
  • brain ischemia
  • cardiovascular mortality
  • cerebrovascular accident
  • clinical outcome
  • drug efficacy
  • drug safety
  • heart infarction
  • human
  • meta analysis
  • non ST segment elevation myocardial infarction
  • platelet reactivity
  • Preferred Reporting Items for Systematic Reviews and Meta-Analyses
  • priority journal
  • quality control
  • randomized controlled trial (topic)
  • sensitivity analysis
  • ST segment elevation myocardial infarction
  • stent thrombosis
  • systematic review


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