Sex related differences in efficacy and safety of antithrombotic therapy in patients with coronary artery disease: systematic review and meta-analysis

OBJECTIVE To evaluate sex related differences in the treatment effect of antithrombotic therapy in patients with established coronary artery disease. DESIGN Systematic review and meta-analysis. DATA SOURCES Ovid Medline and Embase databases from inception to April 2025. INCLUSION CRITERIA Included studies were randomised controlled trials reporting sex stratified outcomes, including ischaemic and major bleeding events, and comparing any experimental versus control antithrombotic strategy in coronary artery disease. DATA EXTRACTION AND SYNTHESIS Two reviewers extracted data and assessed the risk of bias. To avoid ecological bias, a within trial framework was developed to evaluate sex related heterogeneity in the treatment effect of antithrombotic therapies. Sex specific risk estimates were reported as hazard ratios with 95% confidence intervals, whereas trial level ratios of hazard ratios were pooled with an inverse variance model. RESULTS A total of 33 trials enrolling 274 433 participants, of which 72 601 (median proportion 25%) were women, were included. Patients were enrolled between 1999 and 2025. A total of 6018 deaths occurred in 187 580 patients across 22 trials (3064 deaths in patients using more intensive antithrombotic therapies and 2954 in those using less intensive therapies). The relative risk of all cause death was comparable for more intensive versus less intensive antithrombotic therapies in both women and men, without sex based interaction (interaction hazard ratio 1.06, 95% confidence interval 0.94 to 1.19; P for interaction=0.33; I2=0.00%; P for heterogeneity=0.76). 7558 myocardial infarctions occurred among 172 504 patients. More intensive antithrombotic therapies were associated with a reduced risk of myocardial infarction by ~15% in both men and women (interaction hazard ratio 1.05, 0.95 to 1.17; P for interaction=0.36; I2=14.05%; P for heterogeneity=0.28). Conversely, major bleeding was significantly increased by ~40% for more intensive versus less intensive antithrombotic therapies irrespective of sex (interaction hazard ratio 0.99, 0.86 to 1.15; P for interaction=0.93; I2=33.56%; P for heterogeneity=0.05). Overall, 4003 major bleeding events occurred (2384 in patients using more intensive therapies and 1619 in those using less intensive therapies). CONCLUSIONS Antithrombotic therapies in patients with established coronary artery disease provided consistent efficacy and safety outcomes in women and men.