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

Abstract

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.

The association between beta‐blockers and outcomes in patients with heart failure and concurrent Alzheimer's disease and related dementias

“…Recent work, examining whether the association between BB use and outcomes changes as patients age found that, at a population level, BB therapy was associated with lower short and long-term mortality across the age spectrum. 12,13 Consistent with this prior work, we also found that among all patients with HFrEF, regardless of cognitive function, there was a significant association between continuing or newly starting BB therapy after hospitalization and lower rates of 90-day and 1-year mortality. Extending prior work, this study found that this association, between continuing or newly starting BB therapy after HFrEF hospitalization and lower rates of 90-day and 1-year mortality, remained present among patients with HF and ADRD.…”

“…[6][7][8][9][10][11] In addition, recent observational analyses have suggested that the benefit of BB does not wane as patients get older. 12,13 What remains unclear is whether, patients with ADRD, who may be at higher risk for many BB side effects, benefit, on net, as much as those without ADRD.…”

“…As of 2021, the average Medicare beneficiary with heart failure with reduced ejection fraction (HFrEF) is 80 years old. 1,2 Over two-thirds have multiple chronic conditions 3 and 15% have concurrent Alzheimer's Disease or a related dementia (ADRD). As the population ages, this number of patients with concurrent HFrEF and ADRD is expected to increase.…”

“…In large, randomized controlled trials of patients with HFrEF, beta‐blockers (BB) have been shown to decrease mortality and readmission rates 6–11 . In addition, recent observational analyses have suggested that the benefit of BB does not wane as patients get older 12,13 . What remains unclear is whether, patients with ADRD, who may be at higher risk for many BB side effects, benefit, on net, as much as those without ADRD.…”

Heart failure and cognitive impairment: Complexity that requires a new approach

“…3 Cognitive impairment can significantly impair a patient from performing these key tasks, increasing the risk for disease progression and adverse events. The significant and rising prevalence of cognitive impairment 4 and its implications on care support the need to routinely assess cognition when providing care to older adults with HF. This has been recommended by the Geriatric Cardiology Section Leadership Council of the American College of Cardiology.…”