Digitoxin appears to be safe and effective in patients with heart failure with reduced ejection fraction (HFrEF), including those with atrial fibrillation (AFib), according to an analysis from DIGIT-HF, while digoxin discontinuation after long-term treatment was associated with clinical deterioration in patients with HF and LVEF ≤50%, according to an analysis from DECISION. Both were published recently in EHJ.

In the DIGIT-HF trial, Udo Bavendiek, MD, et al., showed that low-dose digitoxin added to guideline-directed medical therapy reduced the risk of the primary composite outcome of all-cause death and first hospitalization for worsening heart failure (HFH) among patients with HFrEF.

In this post-hoc analysis, they compared the occurrence of the primary outcome in patients with (n=330) and without (n=882) AFib at baseline and found that digitoxin significantly reduced the primary composite outcome, with reductions of a similar magnitude for each component, in both groups. The absolute risk reduction for the primary outcome was 9.5% in patients with AFib and 2.8% in patients without AFib. The number needed to treat (NNT) was 11 and 36, respectively, over the 36-month follow-up. However, no significant interaction was found between AFib status and treatment effect.

Looking at all-cause death, the absolute risk reduction was 14.8% and 2.3%, with an NNT of 7 and 4, in those with and without AFib. For HFH, the reductions were consistent between groups.

"Although the formal interaction between [AFib] and treatment did not reach significance, the larger absolute risk reductions and lower [NNT] in the [AFib] subgroup ... suggest that digitoxin may confer particular benefit in this high-risk population," write the authors.

The DECISION trial showed in 1,001 patients with HF (LVEF ≤50%) that low-dose digoxin, compared with placebo, did not significantly reduce the risk of the composite outcome of repeated HFH, repeated urgent HF visits and cardiovascular death at 36 months.

In their prespecified analysis of the DECISION trial, Peter van der Meer, MD, evaluated outcomes in the 587 patients on active treatment at the end of study (288 on digoxin and 299 on placebo) who went through a blinded treatment withdrawal and an in-person follow-up at six weeks.

During the pre-withdrawal phase (100 days), there was a similar rate of cardiovascular death or worsening HF events in the digoxin and placebo groups (5.7 vs. 6.5 per 100 patient-years; rate ratio 0.88; 95% CI, 0.24-3.10).

After treatment withdrawal, there was a substantial increase in the rate of cardiovascular death or worsening HF events in the digoxin group compared with the placebo group (42.8 vs. 5.9 events per 100 patient-years; time-by-treatment interaction p=0.036).

A total of 14 events occurred in the digoxin withdrawal group compared with two events in the placebo withdrawal group. Notably, digoxin withdrawal was also associated with a significant increase in heart rate, a reduction in systolic blood pressure, and an increase in NT-proBNP.

"Discontinuation of long-term low-dose digoxin is associated with clinical deterioration of patients with chronic [HF] and a [LVEF] <50%," write the authors. "These findings warrant caution when stopping low-dose digoxin."