Rigor Reviewed

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Low-dose digoxin in patients with heart failure with reduced or mildly reduced ejection fraction: a randomized controlled trial.

Name: Αlpha¹ Rigor Record — Low-dose digoxin in patients with heart failure with reduced or mildly reduced ejection fraction: a randomized controlled trial.
Item: Low-dose digoxin in patients with heart failure with reduced or mildly reduced ejection fraction: a randomized controlled trial.
Rating: 96
Author: Αlpha¹

van Veldhuisen DJ, Rienstra M, Mosterd A, Alings M, Voors AA, Damman K, van Asselt ADI, Bouvy ML, Schaap J, van der Wall EE, Crijns HJGM, Touw DJ, Hoogslag PAM, van de Swaluw JEC, Schuurman RJ, van der Sluis A, Bondarenko O, Römer TJ, Oosterhof T, Bartels GL, Koudstaal S, Dijkmans PA, Linssen GCM, Aksoy I, Dorman HGR, Schut A, Hemels MEW, Tieleman RG, Lok DJA, Westendorp ICD, Vijver MAT, Voordes GHD, de Vos AH, Maas-Soer EL, Postmus D, Lunter G, Tijssen JGP, van der Meer P

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$Αlpha¹ Rigor Review — 3.75★ (Adequate), 0 critical, 3 high issues for “Low-dose digoxin in patients with heart failure with reduced or mildly reduced ejection fraction: a randomized controlled trial.”$

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Αlpha¹ Editorial

This rigor review was examined and confirmed by Αlpha¹ Editorial · August 15, 2026

Αlpha¹ Rigor Review

Rigor Reviewed

3.75 / 5

Adequate — real issues to address

Interventional Study

Critical

High-priority

How this rating was calculated▸

Started at 5★ — deductions

IntegrityIntegrity concern ×2−1★
ReportingData & code availability partially met−0.25★

Model-reported confidence: highReviewer agreement: highEngine: 7.39.0Source: full text

Not verified in this report

The numeric-impossibility checks (GRIM/GRIMMER/DEBIT/SPRITE) did not run: 12 reported means were read, and their group size is not stated where the values are printed. These checks need the count the mean was averaged over, so none was performed.

Problems surfaced2 types

Numerical inconsistencies1

Values that contradict each other or are impossible for the stated sample: recomputed p-values and test statistics, GRIM/GRIMMER checks on summary numbers, percentages against their own counts, totals against their parts, and estimates against their own confidence intervals.

Internal contradictions in the reported numbersAssessed

Reporting gaps1

Required detail the manuscript never states — study design, biological variables, ethics approval and consent, key resources, statistical reporting, data and code availability, and overall transparency.

Data/code availability incompleteAssessed

This Αlpha¹ Rigor Review uses AI Rigor Reviewers trained on a curated corpus of high-fidelity and retracted papers, with expert supervision and curation. It can still make mistakes; verify each finding against the source before relying on it.

This is a well-conducted, rigorously reported randomized controlled trial. The main methodological strengths are the double-blind placebo-controlled design, pre-specified power analysis, clear reporting of demographics and ethics, and transparent trial registration. The primary weakness is the vague data availability statement and lack of code sharing, which limits reproducibility.

Both reviewers classified the study as interventional (randomized controlled trial), and I adopt that classification. The evaluation covered all eight dimensions; several sub-criteria were marked not applicable for a human clinical trial (e.g., species/strain, housing, IACUC, cell line authentication). The statistics verification recomputed only 4 tests (all consistent); the remaining statistics are unverified. Citation check found no retracted or unresolved references.

6 major claims checked against the paper's own evidence: all adequately supported.

Recomputed 3 tests: 3 consistent, 0 inconsistent; 1 recomputed directly from the reported test statistics, 2 via agent-written checks.

2 integrity concerns flagged (0 high).

Reporting

Eight Dimensions7 pass · 1 warn

The introduction cites the DIG trial, post-hoc analyses suggesting benefit of low SDC, the DIGIT-HF trial, and RATE-AF, establishing the premise. It acknowledges that prior evidence is from post-hoc analyses and that no larger study with low-dose digoxin has been conducted, addressing limitations of prior work. The rationale linking these findings to the study objectives is logical.

Sub-criteria

prior work citedADEQUATE

premise rationaleADEQUATE

limitations addressedADEQUATE

Per reviewer (2) — the votes behind the verdict

PASSReviewer 1· 95% conf

The paper establishes a clear scientific premise by citing prior work (DIG trial, DIGIT-HF, RATE-AF) and provides a logical rationale for testing low-dose digoxin, including addressing limitations of prior post-hoc analyses.

Evidence

paraphrase[Introduction, paragraphs 1-3]

“In 1997, the Digitalis Investigation Group (DIG) trial... demonstrated, that digoxin... did not reduce all-cause mortality... The trial also showed... a significant 28% reduction in hospitalization for worsening heart failure.”

paraphrase[Introduction, paragraph 2]

“Additional post hoc studies from DIG and other databases showed that higher serum digoxin concentrations (SDC) (>1.2 ng ml −1 )... were associated with an increased mortality, while lower SDC were associated with favorable outcomes.”

paraphrase[Introduction, paragraph 3]

“In the present study, we examined the effect of low-dose digoxin against a background of contemporary guideline-recommended treatment in the Digoxin Evaluation in Chronic heart failure: Investigational Study In Outpatients in the Netherlands (DECISION) trial.”

PASSReviewer 2· 90% conf

The paper establishes a clear scientific premise by citing prior research (DIG, DIGIT-HF, RATE-AF) and post hoc analyses, and logically justifies the need for a rigorous trial of low-dose digoxin.

Evidence

paraphrase[Introduction, paragraph 1]

“In 1997, the Digitalis Investigation Group (DIG) trial, a large placebo-controlled study in patients with heart failure with sinus rhythm demonstrated, that digoxin—when added to diuretics and angiotensin-converting enzyme inhibitors—did not reduce all-cause mortality, its primary endpoint.”

direct quote[Introduction, paragraph 2]

“Although these findings suggest that low-dose digoxin might be beneficial and guidelines advocated to avoid SDC >1.2 ng ml −1 (ref. ), no larger study with low-dose digoxin has been conducted in heart failure.”