Blinded digoxin withdrawal in heart failure: events rose within six weeks

Design

Prespecified analysis of blinded withdrawal in the DECISION randomised trial

Population

587 people with heart failure (reduced or mildly reduced ejection fraction) after a median 36.5 months of digoxin or placebo

Primary outcome

Cardiovascular death or worsening heart failure events after withdrawal

Effect

42.8 vs 5.9 events per 100 patient-years; 14 vs 2 events; rate ratio 7.37 (95% CI 1.56 to 34.88)

DECISION randomised 1,001 people with heart failure to low-dose digoxin or placebo for a median of 36.5 months. At the end of the study, 587 who were still on their assigned treatment (288 on digoxin and 299 on placebo) went through a blinded withdrawal with an in-person visit at six weeks. All events were adjudicated.

Before withdrawal, cardiovascular death or worsening heart failure ran at 5.7 per 100 patient-years on digoxin and 6.5 on placebo (rate ratio 0.88, 95% CI 0.24 to 3.10, over 100 days). After withdrawal, the rate climbed to 42.8 per 100 patient-years in those taken off digoxin, against 5.9 in those taken off placebo (interaction P = 0.036). That was 14 events, 12 of them hospitalisations and 2 urgent heart failure visits, against 2 events. The rate ratio was 7.37 (95% CI 1.56 to 34.88). Heart rate and NT-proBNP rose and systolic blood pressure fell after digoxin was stopped.

The authors concluded that stopping digoxin after long-term use is associated with clinical deterioration in heart failure with reduced or mildly reduced ejection fraction, and they advise caution. This is a withdrawal phase with few events, so the interval is wide. It does not show that starting digoxin is right for anyone, and it does not alter guideline recommendations for who should receive it.

• Think twice before stopping long-term digoxin in a stable patient with reduced or mildly reduced ejection fraction.
• If you do stop it, arrange close early follow-up with heart rate, blood pressure, symptoms and NT-proBNP.
• Where toxicity or intolerance forces withdrawal, expect decompensation to be possible within weeks.
• Document why digoxin was started, so later reviews do not remove it as a routine tidy-up of the drug list.

Why it matters

It challenges the assumption that digoxin can be dropped from a regimen already optimised on contemporary therapy without consequence.

Don't overread it

This is a withdrawal analysis of few events; it does not show that starting digoxin improves outcomes in any particular patient.

The statistics, in plain English

The rate ratio of 7.37 sounds large, but it rests on 14 versus 2 events, which is why its interval (1.56 to 34.88) is so wide. The direction is clear; the size is uncertain.

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