Blinded withdrawal of randomized treatment with low-dose digoxin or placebo in heart failure: the DECISION trial

BACKGROUND AND AIMS: Whether digoxin withdrawal is safe in patients with heart failure (HF) optimized on contemporary guideline-recommended medical therapy remains unknown. This prespecified analysis of the DECISION trial evaluated outcomes following blinded withdrawal of digoxin or placebo. METHODS: In DECISION, 1001 patients were randomized to low-dose digoxin or placebo and treated for a median of 36.5 months. At the end of the study, 587 patients on active treatment (digoxin 288, placebo 299) underwent blinded withdrawal with an in-person follow-up visit at six weeks. All events were adjudicated. RESULTS: During the pre-withdrawal phase (100 days), incidence rates of cardiovascular (CV) death or worsening HF events were 5.7 versus 6.5 events per 100 patient-years in the digoxin versus placebo group; rate ratio 0.88:95%CI [0.24-3.10]. Following withdrawal, the incidence rate increased markedly in patients withdrawn from digoxin but not placebo (42.8 vs. 5.9 events per 100 patient-years; time period-by-treatment interaction, P=0.036). Fourteen events (12 hospitalizations and 2 urgent HF visits) occurred in the digoxin withdrawal arm versus two (one HF hospitalization and one CV death) in the placebo withdrawal arm (RR 7.37, 95% CI 1.56-34.88; P=0.012). Withdrawal of digoxin was accompanied by an increase in heart rate (p=0.003), reduction in systolic blood pressure (p=0.014) and rise in NT-proBNP (p=0.002). CONCLUSIONS: Discontinuation of digoxin after long-term treatment is associated with clinical deterioration in patients with HF and a reduced or mildly reduced ejection fraction. These findings warrant caution when stopping digoxin.