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Sex-specific benefits of thromboelastography-guided thromboprophylaxis in peripheral artery disease
Isabella Ferlini Cieri1, Adriana Rodriguez Alvarez1, Andrea Nurko1
1Division of Vascular and Endovascular Surgery, Massachusetts General Hospital, Boston, MA.
Objective:
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.
Methods:
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.
Results:
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.
Conclusions:
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.
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