Digoxin and prognosis of heart failure in older patients with preserved ejection fraction: Importance of heart rate. Results from an observational and multicenter study

Published:October 22, 2018DOI:


      • The role of digoxin in older patients with acute heart failure and preserved ejection fraction remains uncertain.
      • In this type of patients, we found that digoxin was associated with higher risk of 1-year adverse events.
      • However, the prognostic effect of digoxin was dependent of heart rate.
      • Digoxin showed to be related with higher risk at lower heart rates.



      The value of digoxin in heart failure (HF) remains controversial, particularly in patients with preserved ejection fraction (HFpEF). This study evaluated the 1-year risk of events after digoxin treatment for acute heart failure (AHF) in patients >70 years old with HFpEF.


      1833 patients were included in this analysis (mean age, 82 years). The main endpoints were all-cause death and the composite of death and/or HF re-admission within 1 year. Cox regression analysis was used to evaluate the association between digoxin treatment and prognosis.


      401 patients received digoxin treatment; of these, 86% had atrial fibrillation. The mean baseline heart rate was 86 ± 22 bpm. At the 1-year follow-up, 375 patients (20.5%) died and 684 (37.3%) presented composite endpoints. Patients treated with digoxin showed higher rates of death (3.21 vs. 2.44 per 10 person-years, p = .019) and composite endpoint (6.72 vs. 5.18 per 10 person-years, p = .003). After multivariate adjustment, digoxin treatment remained associated with increased risks of death (HR = 1.46, 95% CI: 1.16–1.85, p = .001) and the composite endpoint (HR = 1.35, 95% CI: 1.13–1.61, p = .001). A distinctive prognostic effect of digoxin was found across the heart rate continuum; the risks for both endpoints were higher at lower heart rates and neutral at higher heart rates (p of the interactions = 0.007 and 0.03, respectively).


      In older patients with HFpEF discharged after AHF, digoxin treatment was associated with increased mortality and/or re-admission, particularly in patients with lower heart rates.



      Acute heart failure (AHF), Angiotensin converting enzyme (ACE), Angiotensin receptor blockers (ARBs), Beat per minute (bpm), Ejection fraction (EF), Fractional polynomials (FP), The estimated glomerular filtration rate, based on the Modification of Diet in Renal Disease (eGFR-MDRD), Hazard ratios (HR), Heart failure (HF), Heart failure preserved ejection fraction (HFpEF), Heart failure reduced ejection fraction (HFrEF), Hemoglobin (Hb), Sinus rhythm (SR), Standard deviation (SD), Systolic blood pressure (SBP)
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