Impact of renin-angiotensin-aldosterone system inhibition on morbidity and mortality during long-term continuous-flow left ventricular assist device support: An IMACS report

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 postoperative month 3 without a major adverse event, and categorized patients according to treatment an angiotensin converting enzyme inhibitor (ACEI/ARB) or mineralocorticoid receptor antagonist (MRA). Propensity score matching was performed separately for ACEI/ARB vs none (n=4,118 each) and MRA vs none (n=3,892 each). Of 11,494 patients included, 50% were treated with ACEI/ARB and 38% with MRA. Kaplan-Meier survival was significantly better for patients receiving ACEI/ARB (p < 0.001) but not MRA (p=0.31). In Cox proportional hazards analyses adjusted for known predictors of mortality following LVAD, ACEI/ARB use (hazard ratio 0.81 [95% confidence interval 0.71-0.93], p < 0.0001) but not MRA use (hazard ratio 1.03 [95% confidence interval 0.88-1.21], p=0.69) was independently associated with lower mortality. Among patients treated with an ACEI/ARB, there was a significantly lower unadjusted risk of cardiovascular death (p < 0.001), risk of gastrointestinal bleeding (p=0.01), and creatinine level (p < 0.001). MRA therapy was associated with lower risk of gastrointestinal bleeding (p=0.01) but higher risk of hemolysis (p < 0.01). Potential limitations include residual confounding and therapy crossover. These findings suggest a benefit for ACEI/ARB therapy in patients with heart failure after LVAD implantation.