Female Patients at Increased Risk for Adverse Outcomes after Acute Limb Ischemia.

Objective: The underrepresentation 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 following treatment for acute limb ischemia. However, the reasons for outcome variability are unknown. The objectives of this study were to identify sex specific predictors of major amputation and mortality following intervention for acute limb ischemia and sex specific differences in presentation, management and outcome of patients who undergo revascularization for acute limb ischemia.

Methods: We included all adults who underwent revascularization for ALI at a multihospital healthcare 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: 548 patients were identified, of which 252 (46%) were female. Male patients were younger (64.4±11.5 vs. 67.0 ±15.3; p=0.023), more likely to have CAD (p=0.014), smoking history (p<0.001), and prior revascularization (p<0.001). Female patients were more likely to be hypercoagulable (p=0.001) and less likely to present with acute on chronic disease (p<0.001). Female patients were less frequently on a preoperative statin (p<0.001) or antiplatelet agent (p=0.004). While there was no sex-based difference in Rutherford ALI classification upon presentation, female patients were more likely to go to the OR within 24 hours (p=0.024). 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 (aHR=1.6; 95% CI [1.07-2.33]) analysis. On subgroup analyses, female patients who were medically optimized 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 to males (OR 2.6, p=0.01).

Conclusions: Female patients who presented with ALI had higher mortality following revascularization, except for those medically optimized. They also had notably higher amputation rates following endovascular intervention. Further exploration of these disparities may allow for tailored intervention strategies by sex.