Female patients at increased risk for adverse outcomes after acute limb ischemia

Objective: The under-representation of female patients in key trials results in a lack of sex-based guidelines regarding appropriate evaluation, diagnosis, and management of the female vascular patient. As a result, recent literature has found a difference in the amputation and mortality rates in female patients after treatment for acute limb ischemia (ALI). However, the reasons for outcome variability are unknown. The objectives of this study were to identify sex specific predictors of major amputation and mortality after intervention for ALI and sex-specific differences in the presentation, management, and outcome of patients who undergo revascularization for ALI. Methods: We included all adults who underwent revascularization for ALI at a multihospital health care system (2016-2023), excluding those who presented secondary to trauma, dissection, iatrogenic injury, popliteal aneurysms, or COVID. The terms male and female were used to delineate patient's sex assignment at birth, were obtained from electronic health records, and were assumed to be congruent with gender references. Survival and amputation were evaluated using Kaplan-Meier and multivariable Cox regression with a priori and empirically selected covariates. Comprehensive subgroup analyses were conducted to assess risk of mortality and amputation. Results: We identified 548 patients, of whom 252 (46%) were female. Male patients were younger (64.4 ± 11.5 years vs 67.0 ± 15.3 years; P = .023), more likely to have coronary artery disease (P = .014), a smoking history (P < .001), and a history of prior revascularization (P < .001). Female patients were more likely to be hypercoagulable (P = .001) and less likely to present with acute-on-chronic disease (P < .001). Female patients were less frequently on a preoperative statin (P < .001) or antiplatelet agent (P = .004). Although there was no sex-based difference in Rutherford ALI classification upon presentation, female patients were more likely to go to the operating room within 24 hours (P = .024). There were no differences in the initial surgical approach (endovascular vs open). Female patients had an increased rate of death on univariable (P = .009) and multivariable (adjusted hazard ratio, 1.6; 95% confidence interval, 1.07-2.33) analyses. On subgroup analyses, female patients who were optimized medically on presentation achieved mortality rates similar to male patients. Although there was no difference in overall amputation rates, female patients who underwent an endovascular first approach were twice as likely to undergo amputation in comparison with males (odds ratio, 2.6; P_interaction = .01). Conclusions: Female patients who presented with ALI had higher mortality after revascularization, except for those who were medically optimized. They also had notably higher amputation rates after endovascular intervention. Further exploration of these disparities may allow for tailored intervention strategies by sex.