The association between neurohormonal therapy and mortality in older adults with heart failure with reduced ejection fraction

BACKGROUND/OBJECTIVES: Neurohormonal therapy, which includes beta-blockers and angiotensin-converting enzyme inhibitor/angiotensin receptor blockers (ACEi/ARBs), is the cornerstone of heart failure with reduced ejection fraction (HFrEF) treatment. While neurohormonal therapies have demonstrated efficacy in randomized clinical trials, older patients, which now comprise the majority of HFrEF patients, were underrepresented in those original trials. This study aimed to determine the association between short- (30 day) and long-term (1 year) mortality and the use of neurohormonal therapy in HFrEF patients, across the age spectrum. DESIGN/SETTING/PARTICIPANTS: This is a population-based, retrospective, cohort study between January 2008 and December 2015. We used 100% Medicare Parts A and B and a random 40% sample of Part D to create a cohort of 295,494 fee-for-service beneficiaries with at least one hospitalization for HFrEF between 2008 and 2015. All analyses were performed between May 2019 and July 2020. EXPOSURE: We used Part D data to determine exposure to beta-blocker and ACEi and ARB therapy. RESULTS: We found that in 295,494 patients admitted for HFrEF between 2008 and 2015, the average age was 80 years, 54% were female and 17% were non-white. The baseline mortality rate was higher among those aged ≥85, but the mortality benefits of neurohormonal therapy were preserved across the age spectrum. Among those ≥85 years old, the hazard ratio for death within 30 days was 0.59 (95% confidence interval CI 0.56-0.62; p < 0.001) for beta-blockers and 0.47 (95% CI 0.44-0.49; p < 0.001) for ACEi/ARBs. The hazard ratio for death within 1 year was 0.37-0.56 (95% CI 0.35-0.58; p < 0.001) for beta-blockers and 0.38-0.53 (95% CI 0.37-0.55; p < 0.001) for ACEi/ARB. CONCLUSION: At a population level, neurohormonal therapy was associated with lower short- and long-term mortality across the age spectrum.