What is the clinical evidence from this study?

Study design: Cohort. Population: Heart failure with reduced ejection fraction (HFrEF) (n=1396). Intervention: Digoxin discontinuation vs. Digoxin continuation. Primary outcome: Heart failure readmission at 4 years (HR 1.21, 95% CI 1.05-1.39, p=0.007).

What does this research mean for the field?

Discontinuation of digoxin in hospitalized older patients with HFrEF receiving contemporary guideline-directed medical therapies is associated with significantly increased risks of heart failure readmission and adverse clinical outcomes. Novelty: ClaimNovelty.CONFIRMATORY. Consensus alignment: ConsensusAlignment.NEUTRAL.

What question did this study set out to answer?

To determine the relationship between chronic digoxin discontinuation and clinical outcomes in hospitalized patients with heart failure with reduced ejection fraction receiving contemporary guideline-directed medical therapies.

July 8, 2026Journal of the American College of CardiologyOpen Access

Digoxin Discontinuation and Outcomes in Patients With Heart Failure With Reduced Ejection Fraction

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Key result

Digoxin discontinuation linked to ~21% higher risk of HF readmission in HFrEF.

HR 1.21
95% CI 1.05-1.39
P=0.007
n=1,396

Why the study?

The effects of digoxin discontinuation were well-documented in ambulatory HFrEF patients receiving ACE inhibitors, but outcomes were unclear in hospitalized patients receiving contemporary GDMT including beta-blockers and MRAs.

Does digoxin discontinuation increase the risk of heart failure readmission in hospitalized older patients with HFrEF on contemporary GDMT?

Population

698 propensity-matched pairs of hospitalized HFrEF patients on pre-admission digoxin

Comparison

Digoxin discontinuation vs continuation

Design

Propensity score-matched registry cohort study

Follow-up

Four-year post-discharge

Authors

AMAwais Amjad MalikMayo Clinic RMRavi MassonHoag Memorial Hospital Presbyterian SSSteven SinghHeart Failure & Transplant

Discussion

Member takes

Key expert perspectives

Captured external expert commentary on this paper, strongest first. Original sources are linked where available.

RC Richard CrawfordProfessor of Medicine, University of California San Francisco

“What is interesting about this study was that in the face of modern pharmacologic and device therapy for HFrEF, we may have stopped using digoxin prematurely.”

University of California, San FranciscoNewsletter

Implication

Discontinuing digoxin was associated with higher HF readmission risk in older HFrEF patients; hypothesis-generating and should not yet change practice.

Key Points

To determine the relationship between chronic digoxin discontinuation and clinical outcomes in hospitalized patients with heart failure with reduced ejection fraction receiving contemporary guideline-directed medical therapies.
Analyzed 11,900 hospitalized patients with HFrEF (ejection fraction ≤45%) from Medicare-linked OPTIMIZE-HF, identifying 3,499 receiving pre-admission digoxin, of whom 721 discontinued therapy.
Assembled a propensity score-matched cohort of 698 pairs (1,396 patients; mean age 76 years; mean EF 28%; 41% women; 13% African American; 65% on beta-blockers) balanced across 50 baseline characteristics.
Evaluated heart failure readmission, all-cause readmission, all-cause mortality, and a combined endpoint of HF readmission or all-cause mortality at 30 days, 6 months, 1 year, and 4 years post-discharge.
At 4 years post-discharge, digoxin discontinuation was associated with significantly higher risks of HF readmission (HR, 1.21; 95% CI, 1.05–1.39; p=0.007), all-cause readmission (HR, 1.16; 95% CI, 1.04–1.31; p=0.010), and the combined endpoint (HR, 1.20; 95% CI, 1.07–1.34; p=0.002), but not all-cause mortality (HR, 1.09; 95% CI, 0.97–1.24; p=0.163).
At 30 days post-discharge, digoxin discontinuation was associated with higher risks of all-cause mortality (HR, 1.80; 95% CI, 1.26–2.57; p=0.001) and the combined endpoint (HR, 1.36; 95% CI, 1.07–1.71; p=0.007), but not HF readmission (HR, 1.19; 95% CI, 0.90–1.59; p=0.226) or all-cause readmission (HR, 1.03; 95% CI, 0.84–1.26; p=0.778).
Discontinuation of digoxin was associated with significantly higher risks across all 4 clinical endpoints at 6 months and 1 year post-discharge.

Study Design

Type

Cohort (n=1,396)

Multicenter

Yes

Structured PICO

Does digoxin discontinuation increase the risk of heart failure readmission in hospitalized older patients with HFrEF on contemporary GDMT?

Population

1,396 propensity-matched hospitalized older adults with HFrEF (mean age 76, 41% female) receiving pre-admission digoxin and contemporary GDMT, followed for up to 4 years.

Exposure

Discontinuation of chronic digoxin therapy prior to hospital discharge

Comparator

Continuation of chronic digoxin therapy

Outcome

Heart failure readmission at 4 years post-dischargehard clinical

Main Result

Hazard Ratio: 1.21 (95% CI 1.05–1.39)

p-value: p=0.007

Discontinuing digoxin in older HFrEF patients on contemporary GDMT is associated with increased risks of hospital readmission, suggesting it may be premature to abandon its use.

Limitations

Potential bias due to imbalances in unmeasured baseline characteristics
Based on fee-for-service Medicare beneficiaries, which may limit generalizability
Lack of data on digoxin use during follow-up
Lack of data on the use and uptitration of other HF drugs during follow-up
Potential unmeasured confounding despite propensity matching
Fee-for-service Medicare population limits generalizability
No data on digoxin use during follow-up
No data on uptitration of other HF drugs during follow-up

Cite This Study

Malik et al. (2019) conducted a cohort in Heart failure with reduced ejection fraction (HFrEF) (n=1,396). Digoxin discontinuation vs. Digoxin continuation was evaluated on Heart failure readmission at 4 years (HR 1.21, 95% CI 1.05-1.39, p=0.007). Discontinuation of chronic digoxin therapy in hospitalized older patients with HFrEF was associated with a 21% higher risk of heart failure readmission at 4 years (HR 1.21).

synapsesocial.com/papers/6a4ebec88d6b14ebdbbc88a8 https://doi.org/10.1016/j.jacc.2019.05.064

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Implication

Discontinuing digoxin was associated with higher HF readmission risk in older HFrEF patients; hypothesis-generating and should not yet change practice.