Sex-Related Differences and Predictors of Mortality in Patients Undergoing Major Orthopaedic Surgery: Insights from the ORTHO-START Registry

Sex-related differences in outcomes after major orthopaedic surgery remain under-investigated, and the prognostic relevance of a history of venous thromboembolism (VTE) is unclear. The ORTHO-START registry is a prospective, multicenter study including 1,077 consecutive adults undergoing major orthopaedic surgery (elective hip/knee arthroplasty or urgent hip fracture repair) across six Italian centers between July 2018 and March 2022. Baseline characteristics, perioperative complications, and antithrombotic therapy were collected. The primary outcome was all-cause mortality at 24 months; secondary outcomes were thromboembolic and bleeding events. Multivariable logistic regression identified predictors of mortality. Women represented 72.3% (n = 775) of the cohort and were older than men (80.6 ± 10.0 vs. 76.2 ± 13.0 years, p < 0.001). Urgent procedures comprised 65.6% (n = 706) of surgeries, predominantly involving women (n = 542). At 24 months, mortality was higher in men (31 vs. 18%, p = 0.018). Independent predictors of mortality included male sex (odds ratio [OR] = 2.6, 95% confidence interval [CI]: 1.8-4.0), older age, lower body mass index, urgent surgery (OR = 7.2, 95% CI: 4.1-12.4), and prior VTE (OR = 5.7, 95% CI: 1.4-23.9). Causes of death were known for 160/210 (76.2%): neurological complications were most frequent (25%), followed by cardiovascular disease (21.3%) and immobility-related causes (14.4%); pulmonary embolism accounted for 1.3% of deaths. Thrombotic and hemorrhagic events occurred in both sexes without significant differences. Male sex and a history of VTE are independent predictors of long-term mortality following major orthopaedic surgery. Incorporating these factors into preoperative risk assessment may improve management and postoperative outcomes.