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

OBJECTIVE: To estimate the absolute treatment effects of newer P2Y(12) 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 P2Y(12) 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 P2Y(12) 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 P2Y(12) inhibitors may be slightly less efficacious in women than men, but the absolute risk reduction is similar in both sexes.