Sex-specific benefits of thromboelastography-guided thromboprophylaxis in peripheral artery disease.

Abstract

To evaluate sex-specific differences in clinical outcomes after thromboelastography with platelet mapping (TEG-PM)-guided antiplatelet therapy compared with standard empiric dual antiplatelet therapy in patients undergoing peripheral artery disease revascularization. This prospective cohort study enrolled 443 consecutive patients undergoing lower extremity revascularization at Massachusetts General Hospital (2020-2025). Patients received either TEG-PM-guided antiplatelet adjustment (n = 147; 46 female, 101 male) or standard empiric dual antiplatelet therapy (n = 296; 102 female, 194 male). TEG-PM testing was performed preoperatively and at serial intervals post procedure (1, 3, and 6 months), with antiplatelet therapy adjusted accordingly. Clinical outcomes were followed through 12 months. The primary outcome was major amputation (above-ankle) at 12 months. Secondary outcomes included thrombotic events, all-cause mortality, and amputation-free survival. Sex-stratified analyses and treatment × sex interaction testing were performed. Women receiving TEG-guided therapy demonstrated significantly lower major amputation rates compared with men within the same treatment arm (2.2% vs 16.8%; P = .013; odds ratio, 0.110; 95% confidence interval, 0.014-0.852), representing an 87% relative risk reduction with a number needed to treat of 7. In contrast, no significant sex difference was observed in the standard care arm (18.6% vs 21.1%; P = .614). The treatment × sex interaction approached statistical significance (odds ratio, 0.129; P = .060), suggesting differential treatment response by sex. Women in the TEG-guided arm also demonstrated superior amputation-free survival compared with men (8.7% vs 22.8% events; 62% RRR). TEG-guided therapy reduced thrombotic events overall (5.4% vs 19.3%; log-rank P < .001; hazard ratio, 0.312; 95% confidence interval, 0.156-0.624), with a similar benefit observed in both sexes. Subgroup analyses demonstrated consistent female benefit across high-risk populations, including patients with diabetes, chronic kidney disease, and chronic limb-threatening ischemia. TEG-PM-guided thromboprophylaxis appears to provide greater protection against major amputation in women compared with men after peripheral revascularization. The 87% relative risk reduction in amputation observed in women, with a number needed to treat of 7, represents a clinically meaningful benefit. These findings suggest that a precision medicine approach to antiplatelet therapy may help to address the historical outcomes gap between women and men with peripheral artery disease. Routine TEG-PM monitoring should be considered, particularly in female patients undergoing lower extremity revascularization.