Differences in relative and absolute effectiveness of oral P2Y 12 inhibition in men and women: a meta-analysis and modelling study

Heart. 2018 Apr;104(8):657-664. doi: 10.1136/heartjnl-2017-312003. Epub 2017 Oct 5.

Abstract

Objective: To estimate the absolute treatment effects of newer P2Y12 inhibitors (ticagrelor and prasugrel) compared with clopidogrel in men and women with acute coronary syndrome (ACS).

Methods: We searched Ovid MEDLINE, Embase and the Cochrane Central Register of Controlled Trials for randomised controlled trials of oral P2Y12 inhibitors for acute stroke or ACS. Age-specific and sex-specific mortality was obtained for all patients admitted to hospital with myocardial infarction in Scotland from 2006 to 2010 (prior to introduction of prasugrel or ticagrelor).

Results: From 9277 articles, nine fulfilled our inclusion criteria. Three trials compared newer P2Y12 inhibitors to clopidogrel in ACS, in which the treatment rate ratio (RR) for major adverse cardiovascular events in men was 0.80 (95% CI 0.69 to 0.93). For the same outcome, across all nine trials, the sex-treatment interaction RR was 1.08 (95% CI 0.98 to 1.19). Combining these estimates yielded a treatment RR in women of 0.86 (95% CI 0.72 to 1.04).17 842 women and 27 818 men were admitted to hospital with myocardial infarction. Mortality was higher for women than men for all-cause (5708, 32.0% vs 5891, 21.2%), cardiovascular (4032, 22.6% vs 4117, 14.8%) and bleeding (193, 1.1% vs 228, 0.8%) deaths.On applying the sex-specific RRs to this population, the absolute risk reduction for mortality at 1 year was similar for women and men for all-cause (2.30% (95% CI -0.92% to 5.22%) vs 2.47% (95% CI 0.62% to 4.10%)), cardiovascular (2.70% (95% CI -0.63% to 5.74%)) vs 2.72% (95% CI 0.92% to 4.35%)) and bleeding (-0.27% (95% CI -1.06% to 0.30%) vs -0.18% (95% CI -0.71% to 0.24%)) deaths.

Conclusion: Newer P2Y12 inhibitors may be slightly less efficacious in women than men, but the absolute risk reduction is similar in both sexes.

Keywords: acute coronary syndromes; acute myocardial infarction; epidemiology and meta-analysis.

Publication types

  • Meta-Analysis
  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Acute Coronary Syndrome / drug therapy*
  • Acute Coronary Syndrome / mortality
  • Adolescent
  • Adult
  • Aged
  • Clopidogrel / therapeutic use
  • Female
  • Humans
  • Male
  • Middle Aged
  • Myocardial Infarction / drug therapy
  • Myocardial Infarction / mortality
  • Prasugrel Hydrochloride / therapeutic use
  • Purinergic P2Y Receptor Antagonists / therapeutic use*
  • Randomized Controlled Trials as Topic
  • Risk Factors
  • Scotland / epidemiology
  • Sex Characteristics*
  • Ticagrelor / therapeutic use
  • Treatment Outcome
  • Young Adult

Substances

  • Purinergic P2Y Receptor Antagonists
  • Clopidogrel
  • Prasugrel Hydrochloride
  • Ticagrelor