Withdrawal of low-dose digoxin in heart failure patients increased cardiovascular death or worsening HF events compared to placebo (RR 7.37; 95% CI 1.56-34.88; P=0.012).
RCT (n=1,001)
Blinded
Randomized
Does blinded withdrawal of low-dose digoxin increase cardiovascular death or worsening heart failure in patients with heart failure on contemporary medical therapy?
Discontinuation of low-dose digoxin after long-term treatment in patients with heart failure leads to significant clinical deterioration and increased risk of worsening heart failure events.
Effect estimate: RR 7.37 (95% CI 1.56-34.88)
Absolute Event Rate: 42.8% vs 5.9%
p-value: p=0.012
Abstract 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 Following withdrawal, the incidence rate increased markedly in patients withdrawn from digoxin but not placebo (42.8 vs. 5.9 events per 100 patient-years; time period-by-treatment interaction, P=0.036).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.
“Discontinuation of long-term low-dose digoxin is associated with clinical deterioration of patients with chronic [HF] and a [LVEF] <50%. These findings warrant caution when stopping low-dose digoxin.”
Meer et al. (2026) conducted an RCT in Heart failure (n=1,001). Digoxin withdrawal vs. Placebo withdrawal was evaluated on Cardiovascular death or worsening heart failure events (RR 7.37, 95% CI 1.56-34.88, p=0.012). Withdrawal of low-dose digoxin in heart failure patients increased cardiovascular death or worsening HF events compared to placebo (RR 7.37; 95% CI 1.56-34.88; P=0.012).