Comparative Efficacy and Safety of Oral P2Y12 Inhibitors in Acute Coronary Syndrome: Network Meta-Analysis of 52 816 Patients From 12 Randomized Trials

Circulation. 2020 Jul 14;142(2):150-160. doi: 10.1161/CIRCULATIONAHA.120.046786. Epub 2020 May 29.

Abstract

Background: New randomized, controlled trials have become available on oral P2Y12 inhibitors 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: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42019155648.

Keywords: P2Y12 protein, human; acute coronary syndrome; meta-analysis.

Publication types

  • Meta-Analysis
  • Research Support, N.I.H., Extramural

MeSH terms

  • Acute Coronary Syndrome / complications*
  • Acute Coronary Syndrome / mortality
  • Acute Coronary Syndrome / therapy
  • Cause of Death
  • Hemorrhage
  • Humans
  • Network Meta-Analysis
  • Percutaneous Coronary Intervention
  • Platelet Aggregation Inhibitors / administration & dosage
  • Platelet Aggregation Inhibitors / adverse effects
  • Platelet Aggregation Inhibitors / therapeutic use*
  • Prognosis
  • Purinergic P2Y Receptor Antagonists / administration & dosage
  • Purinergic P2Y Receptor Antagonists / adverse effects
  • Purinergic P2Y Receptor Antagonists / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Thrombosis / etiology*
  • Thrombosis / mortality
  • Thrombosis / prevention & control*
  • Treatment Outcome

Substances

  • Platelet Aggregation Inhibitors
  • Purinergic P2Y Receptor Antagonists