Geographical Difference of the Interaction of Sex with Treatment Strategy in Patients with Multivessel Disease and Left Main Disease: A Meta-Analysis from SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery), PRECOMBAT (Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients with Left Main Coronary Artery Disease), and BEST (Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients with Multivessel Coronary Artery Disease) Randomized Controlled Trials

Background - The impact of sex on clinical outcomes of percutaneous coronary intervention and coronary artery bypass graft for patients with multivessel coronary disease and unprotected left main disease could be dissimilar between Western and Asian populations. Methods and Results - To assess clinical outcomes after percutaneous coronary intervention or coronary artery bypass graft in women and men with multivessel coronary disease and unprotected left main disease, a pooled analysis (n=3280) was performed using the patient-level data from 3 large randomized trials: SYNTAX (Synergy between PCI with Taxus and Cardiac Surgery), PRECOMBAT (Bypass Surgery Versus Angioplasty Using Sirolimus-Eluting Stent in Patients With Left Main Coronary Artery Disease), and BEST (Bypass Surgery and Everolimus-Eluting Stent Implantation in the Treatment of Patients with Multivessel Coronary Artery Disease) trials. The primary end point was all-cause death. Of 3280 patients, 794 patients (24.2%) were women. The median follow-up period was 1806 days (1611-1837 days). In women, a high heterogeneity of the treatment effect among the 3 trials was found for all-cause death (I²>50%), whereas in men, it was consistent across the 3 trials. In the Western trial (SYNTAX), female sex favored coronary artery bypass graft compared with percutaneous coronary intervention (hazard ratio_{(percutaneous coronary intervention)} 2.213; 95% confidence interval, 1.242-3.943; P=0.007), whereas in the Asian women (PRECOMBAT and BEST), the treatment effect was neutral between both strategies. Sex interaction with treatment strategy was evident in the Western trial (P_interaction=0.019) but not in the Asian trials (PRECOMBAT P_interaction=0.469 and BEST P_interaction=0.472; I²=58%). Conclusions - The present meta-analysis suggested the presence of the heterogeneous sex-treatment interaction across Asian and Western trials. Considering the ongoing globalization of our medical practice, the heterogeneity of the sex-treatment interaction needs to be well recognized and taken into account during the decision making of the treatment strategy. Clinical Trial Registrations - URL: https://www.clinicaltrials.gov. Unique identifiers: NCT00114972, NCT00997828, NCT00422968.