The Effect of Renin-Angiotensin-Aldosterone System Inhibition on Morbidity and Mortality during Long-Term Continuous-Flow Left Ventricular Assist Device Support

Abstract

Inhibition of the renin angiotensin-aldosterone system (RAAS) improves survival and reduces adverse cardiac events in heart failure with reduced ejection fraction, but the benefit is not well-defined following left ventricular assist device (LVAD). We analyzed the ISHLT IMACS registry for adults with a primary, continuous-flow LVAD from January 2013 to September 2017 who were alive at post-operative month 3 without a major adverse event, and categorized patients according to treatment at month 3 with an angiotensin converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB), mineralocorticoid receptor antagonist (MRA), or neither (noRAAS). Of 11,494 patients included, 50% were treated with ACEI/ARB and 38% with MRA. Propensity score matching was performed separately for ACEI/ARB versus noRAAS (n=2,853 each) and MRA versus noRAAS (n=2,670 each). Kaplan-Meier survival was significantly better for patients receiving ACEI/ARB (Figure A, p<0.001) and MRA (Figure B, p=0.03). In Cox proportional hazards analyses adjusted for known predictors of survival following LVAD, ACEI/ARB use (HR 0.79 [95% CI 0.69-0.90], p<0.001) but not MRA use (HR 0.94 [95% CI 1.02-1.49], p=0.33) was independently associated with better survival. Among patients treated with an ACEI/ARB, there was a non-significant trend toward less gastrointestinal bleeding (p=0.08) but significantly more hemolysis (p=0.04) at 12 months. Rates of late right heart failure (p=0.41), stroke (p=0.40), dialysis (p=0.29), and NYHA class (p=0.44) at 12 months were similar. Potential limitations include residual confounding and therapy crossover. These findings suggest a benefit for ACEI/ARB as tolerated in patients with heart failure after LVAD implantation.