Multilevel thrombotic or embolic burden and its role in sex-related outcomes in acute limb ischemia

Objective

The impact of sex upon outcomes in acute limb ischemia (ALI) remains disputed. We aim to quantify the effect of sex upon amputation-free survival (AFS) after a percutaneous-first approach for ALI.

Methods

This was a two-center retrospective review of ALI managed via a percutaneous-first approach. Demographics, comorbidities, and clinical characteristics were analyzed. The Kaplan-Meier and Cox regression were used to estimate AFS, limb salvage, and overall survival.

Results

Over 9 years, 170 patients (n = 87, 51% males; median age, 67 [interquartile range (IQR), 59-77 years) presented with ALI. Rutherford classification was I in 56 (33%); IIa in 85 (50%); IIb in 20 (12%), and III in 9 (5%). Thirty-day mortality, major amputation rate, and fasciotomy rates were 8% (n = 13); 6.5% (n = 11), and 4.7% (n = 8), respectively. Among revascularized limbs, 92% were patent at 30 days. Length of stay was 7 days (IQR, 3-11 days). Complications included 13 bleeding episodes (8%), four cases of atrial fibrillation (2%), and three re-thrombosis/clot extension events (1.7%). No differences were noted in complication rates when stratified by sex. Females were older than males (median age, 70 [IQR, 62-79] vs 65 [IQR, 56-76 years]; P = .02) and more likely to present with atrial fibrillation (20.5% vs 8%; P = .02) and hyperlipidemia (72% vs 57%; P = .04). Females also more frequently presented with multi-level thrombotic/embolic burden compared with males (56% vs 43%; P = .03) and required both aspiration thrombectomy and thrombolysis (27% vs 14%; P = .02). Kaplan-Meier estimated median AFS, limb salvage, and overall survival were 425 days (IQR, 140-824 days); 314 days (IQR, 72-727 days); and 342 days (IQR, 112-762 days). When stratified by sex, females had worse survival (median, 270 days [IQR, 92-636 days] vs 406 days [IQR, 140-937 days]; P = .005) and limb salvage (median, 241 days [IQR, 88-636 days] vs 363 days [IQR, 49-822 days]; P = .04) compared with males. Univariate Cox regression showed female sex (hazard ratio [HR], 1.46; 95% confidence interval [CI], 1.04-2.05; P = .03), multi-level thrombotic/embolic burden (HR, 1.64; 95% CI, 1.17-2.31; P = .004), and Rutherford class (HR, 1.37; 95% CI, 1.08-1.73; P = .009) predicted major amputation/death. By multivariable Cox regression, multi-level thrombotic/embolic burden (HR, 1.54; 95% CI, 1.09-2.17; P = .01), Rutherford class (HR, 1.34; 95% CI, 1.07-1.69; P = .01), and female sex (HR, 1.45; 95% CI, 1.03-2.05; P = .03) were each independently predictive of major amputation/death.

Conclusions

A percutaneous-first strategy is safe and efficacious in the overall ALI population. Similar to prior works, female vs male patients with ALI in our cohort have higher rates of mortality and major amputation. In our multivariable model, multi-level thrombotic/embolic burden was independently associated with a greater than 45% increased hazard of major amputation/death at last follow-up. Further prospective analysis is warranted to elucidate the underlying factors contributing to the higher prevalence of multi-level thrombotic/embolic burden in female patients with ALI, and to further define the optimal percutaneous-first approach for ALI in consideration of patient sex and extent of clot burden.