Sex-Based Outcomes with Catheter-Directed and Ultrasound-Assisted Thrombolysis for Acute Limb Ischemia

Female sex has been reported as an independent risk factor negatively associated with rates of limb salvage (LS) and amputation-free survival (AFS) with acute limb ischemia (ALI). This study examines sex-based outcomes with an endovascular-first approach to ALI management.

We conducted a single-center retrospective review of all patients who underwent an endovascular-first approach to ALI between 2013 and 2020. All patients received intra-arterial recombinant tissue plasminogen activator via either catheter-directed thrombolysis infusion with or without ultrasound assistance (EKOS, EkoSonic Endovascular System, Boston Scientific, Marlborough, MA), followed by adjunctive endovascular or surgical revascularization. Primary outcomes included procedural technical success and AFS at 1- and 2-years. Secondary outcomes measured all-cause mortality and rates of LS. Patient demographic, clinical, anatomic, and procedural factors were studied. Univariate analysis was performed using χ² testing, with multivariate analysis via a Cox regression model with variables chosen a priori. Kaplan-Meier (KM) analysis was used to estimate 1- and 2-year outcomes.

During the study period, 79 patients received an endovascular-first approach to ALI. Female sex represented 29% (N = 23) of the cohort. No significant differences were noted between patient sex with respect to burden of medical comorbidities, preoperative use of antiplatelet agents, time (days) to initiation of endovascular ALI management, anatomic extent or underlying occlusive process leading to ALI, length of stay (days), or occurrence of major adverse postoperative events. Rutherford class at presentation included I (N = 28, 35.5%), IIa (N = 49, 62%), and IIb (N = 2, 2.5%); class IIa was the most common stage for each sex [female (N = 14, 61%); male (N = 35, 62.5%)]. Intra-arterial thrombolysis via an ultrasound-assisted thrombolytic device (EKOS, EkoSonic Endovascular System, Boston Scientific, Marlborough, MA) was the initial therapy in 77% of patients, as well as the dominant endovascular therapy for each patient sex [female, N = 16 (69.5%) versus male, N = 45 (80%)]. Procedural technical success was 85%, with a definitive endovascular revascularization performed in the majority of each cohort [female, N = 18 (78%) versus male, N = 50 (89%)]. Technical success of thrombolysis was worse in female patients (female, 69.5% vs male, 91%; P = 0.01), with 21.7% of female patients requiring a definitive open revascularization. Sex-based outcomes of AFS, mortality, and LS were similar at 1- and 2-years on univariate analysis and KM estimates. Female patients displayed a trend toward increased mortality at both 1 year (female, 17.4% vs male, 5.4%; P = 0.08) and 2 years (female, 21.7% vs male, 7.1%; P = 0.06). On multivariate analysis, AFS favored male patients (adjusted hazard ratio: 0.21; 95% confidence interval: 0.44-0.97; P = 0.046).

An endovascular-first approach in the management of ALI is a safe and efficacious treatment option with high rates of technical success. Intra-arterial thrombolysis as the initial endovascular therapy is associated with worse technical success in female patients, with AFS favoring male patients. Patient sex and the presence of multi-level thromboembolic occlusion should be considered when choosing the endovascular therapy for ALI management, with our institutional data supporting an adjunctive not primary role for intra-arterial thrombolysis in female patients.