Differences in relative and absolute effectiveness of oral P2Y₁₂ inhibition in men and women: a meta-analysis and modelling study

Objective
To estimate the absolute treatment effects of newer P2Y12 inhibitors (ticagrelor and prasugrel) compared to clopidogrel in men and women with acute coronary syndrome (ACS).
Methods
We searched Ovid MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (CENTRAL) for randomised controlled trials of oral P2Y12 inhibitors for acute stroke or ACS. Age 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 9,277 articles, 9 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 9 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% versus 5891,21.2%), cardiovascular
(4032, 22.6% versus 4117, 14.8%) and bleeding (193, 1.1% versus 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) versus 2.47% (95% CI 0.62 to 4.10)), cardiovascular (2.70% (95% CI -0.63 to 5.74)) versus 2.72% (95% CI 0.92 to 4.35)) and bleeding (-0.27% (95% CI -1.06 to 0.30) versus -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.