Association of Renin-Angiotensin-Aldosterone System Inhibitor Usage Patterns with Midterm Amputation-Free Survival after Lower Extremity Bypass for Peripheral Arterial Disease

Abstract

Different renin-angiotensin-aldosterone system inhibitor (RAASI) usage patterns exist among patients undergoing lower extremity bypass (LEB) for peripheral arterial disease. We studied the association of RAASI usage patterns with LEB outcomes to determine which pattern is associated with improved survival after LEB. We evaluated peripheral arterial disease patients who underwent LEB between January 2014 and December 2018 in the Vascular Quality Initiative-Medicare matched database. Study cohorts included no RAASI use, preoperative RAASI use only, postoperative RAASI use only, and continuous RAASI use both preoperatively and postoperatively. Logistic and Cox regression was used to adjust for potential confounders. Primary outcome was 2-year amputation-free survival (AFS). Of 19,012 patients included, 1,574 (8.3%) were on RAASIs preoperatively only, 1,051 (5.5%) postoperatively only, and 8,484 (45.2%) continuously. Compared to no RAASI use, isolated preoperative RAASI use was associated with 2.8-fold increased odds of 30-day mortality (adjusted Odds Ratio, 2.75; 95% confidence interval [CI], 2.15-3.51; P<0.001) whereas continuous RAASI use had 56% lower odds of 30-day mortality (adjusted Odds Ratio, 0.44; 95% CI, 0.34-0.58; P<0.001). Two-year AFS was 63.2% for no RAASI use and 60.4%, 66.2%, and 73.4% for preoperative, postoperative, and continuous RAASI use, respectively (P<0.001). While no RAASI use and postoperative RAASI use had comparable adjusted risks of 2-year major amputation or death (adjusted Hazard Ratio [aHR], 0.94; 95% CI, 0.83-1.06; P=0.312), this risk was 14% higher for preoperative RAASI use only (aHR, 1.14; 95% CI, 1.04-1.26; P=0.006) and 23% lower for continuous RAASI use (aHR, 0.77; 95% CI, 0.72-0.82; P<0.001). Isolated preoperative RAASI use was associated with worse 30-day mortality and 2-year AFS, while continuous RAASI use was associated with improved 30-day mortality and 2-year AFS. Optimum survival benefit may be derived from continuous RAAS inhibition in the preoperative and postoperative periods.