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Navarese EP, Khan SU, Kolodziejczak M, et al. 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. (Systematic review)

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.

Discipline Area Score
Cardiology 7 / 7
Family Medicine (FM)/General Practice (GP) 6 / 7
General Internal Medicine-Primary Care(US) 6 / 7
Internal Medicine 6 / 7
Comments from MORE raters

Cardiology rater

There need to be caution with the results of this network (in-direct comparison) meta-analysis. The findings are somewhat discordant compared to the resent ISAR-REACT 5 trial, the largest trial comparing ticagrelor with prasugrel.

Family Medicine (FM)/General Practice (GP) rater

Primary care is typically not initiating these medications, but it's worth being aware of the comparative benefits and risks.

Internal Medicine rater

Meta-analysis looking at the major oral P2Y12 platelet inhibitors used in ACS. Both prasugrel and ticagrelor reduced stent thrombosis compared with clopidogrel at the price of increased major bleeding. Ticagrelor but not prasugrel reduced total and CV mortality compared with clopidogrel, but there was no significant difference between the two newer agents. It's speculated that the reversibility of the anti-platelet effect of ticagrelor was helpful.

Internal Medicine rater

Well done systematic review and NMA.
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