Publications of the Week, August 10


Comparison of different types of P2Y12 inhibitors in acute coronary syndrome

Navarese EP, Khan SU, Kołodziejczak 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. PMID: 32468837.

In patients with an acute coronary syndrome who are receiving acetylsalicylic acid (ASA), there are 3 oral P2Y12 inhibitors that have been studied as a complementary antiplatelet therapy: clopidogrel, prasugrel, and ticagrelor. Although clopidogrel is widely used, the newer P2Y12 inhibitors (prasugrel and ticagrelor) are more potent antiplatelet agents, have a faster onset of action, and carry a lesser potential for interindividual variability in terms of therapeutic effect. This meta-analysis compared the efficacy and safety profile of clopidogrel, prasugrel, and ticagrelor in patients with an acute coronary syndrome when added to ASA therapy.

A network meta-analysis and direct pairwise comparison analysis were done to assess the efficacy and safety outcomes from 12 randomized controlled trials that involved 52,816 patients with an acute coronary syndrome.

  1. Mortality: As compared with clopidogrel, ticagrelor was associated with a significant reduction in 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 prasugrel did not confer a reduction in cardiovascular mortality (HR, 0.90; 95% CI, 0.80-1.01) or all-cause mortality (HR, 0.92; 95% CI, 0.84-1.02).
  2. Ischemic outcomes: When compared with clopidogrel, prasugrel was associated with a significant reduction in myocardial infarction (HR, 0.81; 95% CI, 0.67-0.98), whereas ticagrelor was not associated with a reduced risk for myocardial infarction (HR, 0.97; 95% CI, 0.78-1.22). The risk for definite or probable stent thrombosis was significantly reduced by both prasugrel (HR, 0.50; 95% CI, 0.38-0.64) and ticagrelor (HR, 0.72; 95% CI, 0.58-0.90).
  3. Bleeding: Both prasugrel (HR, 1.26; 95% CI, 1.01-1.56) and ticagrelor (HR, 1.27; 95% CI, 1.04-1.55) were associated with a significantly higher risk for major bleeding than clopidogrel.

When prasugrel was compared with ticagrelor, there were no differences in efficacy and safety but prasugrel was associated with a nonsignificant higher rate of cardiovascular mortality (HR, 1.10; 95% CI, 0.94-1.29) and all-cause mortality (HR, 1.12; 95% CI, 0.98-1.28).

The authors concluded that prasugrel and ticagrelor are more effective than clopidogrel in reducing the risk for ischemic outcomes but both agents confer a higher bleeding risk than clopidogrel; as compared with clopidogrel, a greater mortality reduction was observed with ticagrelor than with prasugrel; and no significant differences were apparent between prasugrel and ticagrelor in the explored outcomes.

See also
  • Publications of the Week, July 27 A digest of noteworthy publications curated by editors from McMaster University. This week’s focus: the HALT-IT trial, investigating the use of tranexamic acid in patients with gastrointestinal bleeding.
  • Publications of the Week, July 13 A digest of noteworthy publications curated by editors from McMaster University. This week’s focus: triple vs dual therapy with or without glucocorticoids in moderate to very severe COPD.
  • Publications of the Week, June 29 A digest of noteworthy publications curated by editors from McMaster University. This week’s focus: benefits of comprehensive disease-modifying pharmacologic therapies in patients with heart failure with reduced ejection fraction.

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