Neurohormonal Blockade and Clinical Outcomes in Patients With Heart Failure Supported by Left Ventricular Assist Devices

This registry-based cohort study analyzes the association between varying combinations of neurohormonal blockade therapies and survival and quality of life in adult patients with left ventricular assist devices. Key PointsQuestionDoes the association between the use of neurohormonal blockade (NHB) and improved clinical outcomes among patients with heart failure with reduced ejection fraction extend to patients with left ventricular assist devices (LVADs)? FindingsIn this cohort study of 12144 patients with LVADs in the Interagency Registry for Mechanically Assisted Circulatory Support between January 2008 and June 2016, use of NHB was associated with significantly lower risk of death and higher quality of life compared with patients not receiving NHB. Survival at 4 years was greatest among patients receiving combination therapy with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, beta-blocker, and mineralocorticoid antagonist. MeaningUse of NHB is associated with improved survival and quality of life among patients with LVADs, suggesting the potential for synergy between intensive NHB and mechanical unloading for patients with advanced heart failure. ImportanceLeft ventricular assist devices (LVADs) improve outcomes in patients with advanced heart failure, but little is known about the role of neurohormonal blockade (NHB) in treating these patients. ObjectiveTo analyze the association between NHB blockade and outcomes in patients with LVADs. Design, Setting, and ParticipantsThis retrospective cohort analysis of the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) included patients from more than 170 centers across the United States and Canada with continuous flow LVADs from 2008 to 2016 who were alive with the device in place at 6 months after implant. The data were analyzed between February and November 2019. ExposuresPatients were stratified based on exposure to NHB and represented all permutations of the following drug classes: angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, beta-blockers, and mineralocorticoid antagonists. Main Outcomes and MeasuresThe outcomes of interest were survival at 4 years and quality of life at 2 years based on Kansas City Cardiomyopathy Questionnaire scores and a 6-minute walk test. ResultsA total of 12144 patients in INTERMACS met inclusion criteria, of whom 2526 (20.8% ) were women, 8088 (66.6%) were white, 3024 (24.9%) were African American, and 753 (6.2%) were Hispanic; the mean (SD) age was 56.8 (12.9) years. Of these, 10419 (85.8%) were receiving NHB. Those receiving any NHB medication at 6 months had a better survival rate at 4 years compared with patients not receiving NHB (56.0%; 95% CI, 54.5%-57.5% vs 43.9%; 95% CI, 40.5%-47.7%). After sensitivity analyses with an adjusted model, this trend persisted with patients receiving triple therapy with an angiotensin-converting enzyme inhibitor or angiotensin receptor blocker, beta-blocker, and mineralocorticoid antagonist having the lowest hazard of death compared with patients in the other groups (hazard ratio, 0.34; 95% CI, 0.28-0.41). Compared with patients not receiving NHB, use of NHB was associated with a higher Kansas City Cardiomyopathy Questionnaire score (66.6; bootstrapped 95% CI, 65.8-67.3 vs 63.0; bootstrapped 95% CI, 60.1-65.8; P=.02) and a 6-minute walk test (1103 ft; bootstrapped 95% CI, 1084-1123 ft vs 987 ft; bootstrapped 95% CI, 913-1060 ft; P<.001). Conclusions and RelevanceAmong patients with LVADs who tolerated NHB therapy, continued treatment was associated with improved survival and quality of life. The optimal heart failure regimen for patients after LVAD implant may be the initiation and continuation of guideline-directed medical therapy. (c) 2019 American Medical Association. All rights reserved.