High-intensity statin therapy reduces risk of amputation and reintervention among patients undergoing lower extremity bypass for chronic limb-threatening ischemia

Objective: Statins are considered standard-of-care medical therapy for patients undergoing lower extremity bypass (LEB) procedures for chronic limb-threatening ischemia (CLTI). It is unclear, however, whether up-titrating and maintaining patients on higher-intensity statin medications following LEB improves limb salvage outcomes. This study was designed to evaluate whether high-intensity statin therapy impacts the risk of amputation and reintervention following LEB for patients with CLTI. Methods: The IBM MarketScan database was used to identify adult patients (18-99 years old) who underwent a LEB for CLTI between 2008 and 2017. Patients lacking insurance covering drug reimbursement or those who already had undergone amputation before time of bypass were excluded. Using pharmacy claims and national drug codes to define statin intensity, patients were stratified into three groups: high-intensity, low-intensity, and limited statin therapy. The association between intensity of statin therapy and need for reintervention and/or major amputation after LEB was analyzed using Kaplan-Meier curves and risk-adjusted Cox proportional hazard models. Results: A total of 25,907 patients who underwent LEB for CLTI were identified, of which 6696 (26%) were maintained on high-dose statins, 9297 (36%) were on low-dose statins, and 9914 (38%) had inconsistent pharmacy claims for statin therapy after surgery. Patients on high-intensity statins were, on average, younger and more likely to be male with comorbid disease (diabetes, hypertension, hyperlipidemia, obesity, renal insufficiency, ischemic heart disease, cerebrovascular disease, and tobacco abuse) than patients on low-intensity statins or limited statin therapy (P < .001 for all comparisons). Following LEB, 6649 patients (25.6%) required a reintervention, and 2550 patients (9.8%) went on to have a major amputation during follow-up. Patients maintained on high-intensity statins after LEB had a significantly lower likelihood of requiring a reintervention (hazard ratio [HR], 0.48; 95% confidence interval [CI], 0.45-0.51; P < .001) or amputation (HR, 0.27; 95% CI, 0.24-0.30; P < .001) as compared with patients on limited statin therapy. Further, there was a dose-dependent effect for these outcomes relative to patients on low-intensity statins in risk-adjusted models, and it was independent of whether an autologous vein graft was used for the LEB. Finally, among patients who underwent a reintervention, high-dose statin therapy also significantly reduced the HR for subsequent amputation (HR, 0.21; 95% CI, 0.18-0.25; P < .001). Conclusions: Patients with CLTI on high-intensity therapy following LEB had a significantly lower risk of requiring subsequent reintervention and amputation when compared with patients on low-intensity statins or with limited statin use. These data suggest that patients with CLTI should be up-titrated and/or maintained on high-intensity statins following revascularization whenever possible.