Low-Dose Digoxin Fails to Reduce Heart Failure Events in Major RCT
The DECISION trial finds low-dose digoxin did not significantly cut hospitalizations or cardiovascular death in 1,001 HFrEF/HFmrEF patients.
Summary
The DECISION trial tested whether low-dose digoxin — one of medicine's oldest heart drugs — could reduce hospitalizations and deaths in heart failure patients. Over 1,001 patients with reduced or mildly reduced heart function were randomized to digoxin or placebo for a median of three years. While digoxin showed a modest, numerically favorable trend in reducing worsening heart failure events, the results did not reach statistical significance. Cardiovascular death rates were nearly identical between groups. Digoxin was generally safe and well tolerated at low doses. The trial provides the most rigorous evidence to date that digoxin should not be routinely added to modern heart failure therapy, though it does not raise major new safety alarms at low serum concentrations.
Detailed Summary
Digoxin has been used in heart medicine for over two centuries, but its role in contemporary heart failure management remained contested. Earlier observational data suggested low serum concentrations might offer benefit without the toxicity seen at higher doses, yet no modern rigorous randomized trial had tested this hypothesis — until now.
The DECISION trial enrolled 1,001 patients with symptomatic chronic heart failure and a left ventricular ejection fraction of 50% or less, randomizing them to low-dose digoxin targeting serum levels of 0.5–0.9 ng/mL or placebo. Mean participant age was 72 years, 28% were women, and 29% had atrial fibrillation. Follow-up extended a median of 36.5 months across multiple Dutch cardiology centers in this double-blind, placebo-controlled design.
The primary composite endpoint — total worsening heart failure hospitalizations, urgent visits, and cardiovascular mortality — occurred at a rate ratio of 0.81 (95% CI 0.61–1.07, P=0.133), falling short of statistical significance. Worsening heart failure events alone trended toward reduction (rate ratio 0.76), and cardiovascular mortality was nearly identical: 17% vs. 18%. Results were consistent across men and women.
For clinicians, these results are clarifying: despite a numerically favorable trend, low-dose digoxin does not provide a statistically meaningful benefit on top of modern guideline-directed therapy. The drug should not be routinely added to heart failure regimens based on this evidence, though the safety profile at low doses was reassuring.
Important caveats include that the trial was potentially underpowered to detect the modest effect sizes observed, and the study population was predominantly older and Dutch, which may limit generalizability. The summary here is based on the published abstract only, and full subgroup and secondary analyses await complete manuscript review.
Key Findings
- Low-dose digoxin did not significantly reduce the composite of HF hospitalizations and cardiovascular death (rate ratio 0.81, P=0.133).
- Worsening heart failure events trended lower with digoxin (rate ratio 0.76) but did not reach significance.
- Cardiovascular mortality was nearly identical: 17% digoxin vs. 18% placebo over ~3 years.
- Low-dose digoxin was safe and well tolerated, with consistent results in both men and women.
- Trial provides first modern double-blind RCT evidence against routine digoxin use in HFrEF/HFmrEF.
Methodology
DECISION was a double-blind, placebo-controlled RCT enrolling 1,001 patients with HFrEF or HFmrEF (EF ≤50%) across multiple Dutch centers. Participants were randomized 1:1 to low-dose digoxin (target serum level 0.5–0.9 ng/mL) or placebo with a median follow-up of 36.5 months. The primary endpoint was a composite of total worsening HF events and cardiovascular mortality, analyzed using a rate ratio approach.
Study Limitations
The trial may have been underpowered to detect the modest absolute treatment effect suggested by the point estimates, as the confidence interval includes potentially clinically meaningful reductions. The study population was predominantly older, European patients, limiting generalizability to younger or more diverse populations. This summary is based on the published abstract only; full data, subgroup analyses, and secondary endpoints are not yet available for review.
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