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Original Investigation
November 18, 2019

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

Author Affiliations
  • 1Department of Internal Medicine, Yale University School of Medicine, Yale University and Yale University School of Medicine, New Haven, Connecticut
  • 2Center for Outcomes Research & Evaluation, Yale University and Yale University School of Medicine, New Haven, Connecticut
  • 3Yale Cardiovascular Research Center, Yale University and Yale University School of Medicine, New Haven, Connecticut
  • 4Department of Computer Science, Yale University and Yale University School of Medicine, New Haven, Connecticut
  • 5Section of Cardiovascular Medicine, Yale University and Yale University School of Medicine, New Haven, Connecticut
  • 6Yale National Clinical Scholars Program, Yale University and Yale University School of Medicine, New Haven, Connecticut
  • 7Veterans Affairs Connecticut Health Care System, Yale University School of Medicine, New Haven, Connecticut
  • 8Section of Cardiothoracic Surgery, Yale University and Yale University School of Medicine, New Haven, Connecticut
JAMA Cardiol. Published online November 18, 2019. doi:https://doi.org/10.1001/jamacardio.2019.4965
Key Points

Question  Does 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)?

Findings  In this cohort study of 12 144 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, β-blocker, and mineralocorticoid antagonist.

Meaning  Use 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.

Abstract

Importance  Left 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.

Objective  To analyze the association between NHB blockade and outcomes in patients with LVADs.

Design, Setting, and Participants  This 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.

Exposures  Patients were stratified based on exposure to NHB and represented all permutations of the following drug classes: angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, β-blockers, and mineralocorticoid antagonists.

Main Outcomes and Measures  The 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.

Results  A total of 12 144 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, 10 419 (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, β-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 Relevance  Among 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.

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