Efficacy and safety of low-dose digoxin in patients with heart failure. Rationale and design of the DECISION trial

Eur J Heart Fail. 2024 Oct;26(10):2223-2230. doi: 10.1002/ejhf.3428. Epub 2024 Aug 30.

Abstract

Aims: Digoxin is the oldest drug in cardiovascular (CV) medicine, and one trial conducted >25 years ago showed a reduction in heart failure (HF) hospitalizations but no effect on mortality. However, later studies suggested that the dose of digoxin used in that trial (and other studies) may have been too high. The DECISION (Digoxin Evaluation in Chronic heart failure: Investigational Study In Outpatients in the Netherlands) trial will examine the efficacy and safety of low-dose digoxin in HF patients with reduced or mildly reduced left ventricular ejection fraction (LVEF) with a background of contemporary HF treatment.

Methods: The DECISION trial is a randomized, double-blind, parallel-group, placebo-controlled event-driven outcome trial which will investigate the efficacy and safety of low-dose digoxin in patients with chronic HF and LVEF <50%. Both patients with sinus rhythm and atrial fibrillation will be enrolled and will be randomized (1:1) to low-dose digoxin or matching placebo. To maintain a target serum digoxin concentration of 0.5-0.9 ng/ml, dose adjustments are made throughout follow-up based on serum digoxin measurements with dummy values for the placebo group. The primary endpoint is a composite of CV mortality and total HF hospitalizations or total urgent hospital visits for worsening HF, and all endpoints are adjudicated blindly by a Clinical Event Committee. The estimated sample size was 982 patients who will be followed for a median of 3 years, and in December 2023 enrolment was completed after 1002 patients.

Conclusions: The DECISION trial will provide important evidence regarding the effect of (low-dose) digoxin on CV mortality and total HF hospitalizations and urgent hospital visits when added to contemporary HF treatment of patients with reduced or mildly reduced LVEF.

Clinical trial registration: ClinicalTrials.gov identifier: NCT03783429.

Keywords: Digoxin; Heart failure; Hospitalizations; Low‐dose; Mortality; Randomized clinical trial.

Publication types

  • Randomized Controlled Trial

MeSH terms

  • Aged
  • Cardiotonic Agents* / administration & dosage
  • Cardiotonic Agents* / therapeutic use
  • Digoxin* / administration & dosage
  • Digoxin* / adverse effects
  • Digoxin* / therapeutic use
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Female
  • Heart Failure* / drug therapy
  • Heart Failure* / mortality
  • Heart Failure* / physiopathology
  • Hospitalization / statistics & numerical data
  • Humans
  • Male
  • Middle Aged
  • Netherlands / epidemiology
  • Stroke Volume* / physiology
  • Treatment Outcome
  • Ventricular Function, Left / drug effects
  • Ventricular Function, Left / physiology

Substances

  • Digoxin
  • Cardiotonic Agents

Associated data

  • ClinicalTrials.gov/NCT03783429