Heart failure (HF) is common, disabling and associated with an impaired survival. In the Netherlands there are currently 165,000 patients with HF, and the prevalence and incidence are increasing. Despite major advances in treatment, the prognosis is still poor, and worse than breast or bowel cancer. In addition, HF is also a very costly disease, mainly caused by HF hospitalizations, accounting for approx.2 percent of the total health care budget in The Netherlands.
Digoxin is the oldest, market-authorized drug for heart failure (HF), and very cheap, however the clinical use of digoxin has largely diminished in the last decade. The only large trial with digoxin, the DIG trial, revealed a highly significant reduction in HF hospitalizations, but no effect on mortality. A post-hoc analysis of the DIG trial suggests that low digoxin concentrations (0.5-0.9ng/mL) may not only improve HF hospitalizations but also mortality, whereas higher concentrations (greater than 1.0ng/mL) were associated with higher mortality. To confirm these retrospective analyses, a prospective, randomized, placebo-controlled trial is necessary to establish the position of digoxin in the contemporary treatment of HF.
We propose to study whether in chronic HF compared to placebo, low-level digoxin reduces (repeated) HF hospitalizations and cardiovascular mortality, on top of guideline-recommended therapies, during median follow-up of 3 years. The DECISION trial will be a national, multicentre (38 sites), randomized, double-blind, placebo controlled, clinical trial. We include 982 chronic HF patients, NYHA II-ambulatory IV, with LVEF less than 50%, on guideline-recommended therapies, with at least one-third of patients with AF, and one-third women, to ensure a sample of the real-life HF population. Digoxin will be given orally starting at doses of 0.2mg, or lower based on age and renal function. Dose adjustments will be made to reach the target serum digoxin concentration range of 0.5-0.9ng/mL.