June 3, 2026Journal of the American College of Cardiology
Randomized study assessing the effect of digoxin withdrawal in patients with mild to moderate chronic congestive heart failure: Results of the PROVED trial
Key result
Digoxin withdrawal increases treatment failures by ~105% and worsens exercise capacity in chronic HF.
- P=0.039
- n=88
Why the study?
Digoxin was a traditional heart failure therapy, but methodologic limitations in earlier studies prevented definitive conclusions regarding its efficacy in chronic, stable mild to moderate heart failure.
Does continuation of digoxin prevent worsening of maximal exercise capacity and treatment failure in patients with mild to moderate chronic heart failure?
Population
Patients with chronic, stable mild to moderate heart failure, LV systolic dysfunction, and sinus rhythm on diuretics and digoxin
Comparison
Digoxin withdrawal (placebo, n = 46) vs digoxin continuation (n = 42)
Design
Prospective, randomized, double-blind, placebo-controlled multicenter trial
Authors
Discussion
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Key expert perspectives
Captured external expert commentary on this paper, strongest first. Original sources are linked where available.
WBWilliam B. Hood Jr.Cardiologist, University of Washington, Seattle
“It's probably not first-line therapy. It's not very powerful. But it's available for patients who are not fully responsive to other agents that have become first-line treatments, such as the ACE inhibitors, β-blockers, spironolactone, and the angiotensin receptor blockers.”
Implication
Digoxin continuation preserves exercise capacity in mild-moderate HF; confirms maintenance benefit in sinus rhythm.
Key Points
- This research aims to assess the efficacy of digoxin in patients with chronic, mild to moderate heart failure.
- Prospective, randomized, double-blind, placebo-controlled trial.
- Patients received either digoxin (n=42) or placebo (n=46).
- Inclusion of patients with chronic, stable heart failure secondary to left ventricular systolic dysfunction.
- Digoxin withdrawal led to a median decrease in exercise capacity of 96 seconds compared to a 4.5-second increase in the digoxin group (p=0.003).
- The incidence of treatment failures was higher in the digoxin withdrawal group (39%) compared to the maintenance group (19%) (p=0.039).
- Patients on digoxin had a lower heart rate (p=0.003) and higher left ventricular ejection fraction (p=0.016).
Study Design
Type
RCT (n=88)
Blinding
Double-blind
Randomization
randomized
Multicenter
Yes
Structured PICO
Does continuation of digoxin prevent worsening of maximal exercise capacity and treatment failure in patients with mild to moderate chronic heart failure?
P
Population
88 patients with chronic, stable mild to moderate heart failure secondary to left ventricular systolic dysfunction, normal sinus rhythm, and receiving long-term diuretics and digoxin.
I
Intervention
Continuation of digoxin therapy
C
Comparator
Withdrawal of digoxin (placebo)
O
Outcome
Maximal exercise capacity (change in exercise time)surrogate
Main Result
Absolute Event Rate: 39% vs 19%
p-value: p=0.039
In patients with mild to moderate heart failure and normal sinus rhythm, withdrawal of digoxin leads to worsened exercise capacity and increased treatment failures.
Cite This Study
Uretsky et al. (1993) conducted an RCT in chronic, stable mild to moderate heart failure (n=88). Digoxin withdrawal vs. Digoxin continuation was evaluated on treatment failures (p=0.039). Withdrawal of digoxin in patients with mild to moderate chronic heart failure increased the incidence of treatment failures (39% vs 19%, p=0.039) and worsened maximal exercise capacity.