Prespecified analysis of the DECISION trial: 1,001 heart failure patients on contemporary guideline therapy were randomised to low-dose digoxin or placebo, with a median treatment of 36.5 months. At study end, 587 patients on active treatment (288 digoxin, 299 placebo) underwent blinded withdrawal with 6-week follow-up. During the 100 days before withdrawal, cardiovascular death/HF event rates were similar (5.7 vs 6.5 events per 100 patient-years). After withdrawal, the rate rose sharply in the digoxin arm but not in the placebo arm (42.8 vs 5.9 per 100 patient-years; time-by-treatment interaction p=0.036). 14 events occurred in the digoxin withdrawal arm (12 hospitalisations, 2 urgent HF visits) versus 2 in the placebo withdrawal arm (RR 7.37; 95% CI 1.56-34.88; p=0.012). Withdrawal was accompanied by higher heart rate, lower systolic BP, and rising NT-proBNP. Conclusion: caution is warranted when stopping long-standing digoxin in HF with (mildly) reduced ejection fraction.
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.
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 Following withdrawal, the incidence rate increased markedly in patients withdrawn from digoxin but not placebo (42.8 vs. 5.9 events per 100 patient-years; time period-by-treatment interaction, P=0.036).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).
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.
