Withdrawal of long-term digoxin therapy was associated with worsening heart failure (HF) outcomes in patients with reduced or mildly reduced ejection fraction, according to findings from the DECISION trial published in the European Heart Journal.

The DECISION study randomized 1001 patients to receive low-dose digoxin or placebo and followed them for a median duration of 36.5 months. At the end of the treatment phase, 587 patients receiving active therapy underwent blinded withdrawal, including 288 patients previously assigned to digoxin and 299 assigned to placebo. Patients attended an in-person follow-up visit six weeks after treatment discontinuation, and all cardiovascular events were independently adjudicated.

During the 100-day period before withdrawal, incidence rates of cardiovascular death or worsening HF events were comparable between treatment groups, occurring at 5.7 versus 6.5 events per 100 patient-years in the digoxin and placebo groups, respectively (rate ratio 0.88; 95% confidence interval [CI] 0.24-3.10).

Following treatment withdrawal, event rates increased substantially among patients withdrawn from digoxin but remained stable in the placebo group. Incidence rates after withdrawal were 42.8 versus 5.9 events per 100 patient-years, respectively, with a significant time period-by-treatment interaction (P=0.036).

A total of 14 events occurred after digoxin withdrawal, including 12 HF hospitalizations and 2 urgent HF visits, compared with two events in the placebo withdrawal arm, consisting of one HF hospitalization and one cardiovascular death (rate ratio 7.37; 95% CI 1.56-34.88; P=0.012).
Withdrawal of digoxin was also associated with increased heart rate (P=0.003), lower systolic blood pressure (P=0.014), and higher NT-proBNP levels (P=0.002).

The findings indicate that discontinuation of long-term digoxin therapy may be associated with clinical deterioration in patients with HF. The study authors noted that caution may be warranted when considering digoxin withdrawal.