Digoxin Misses Heart Failure Endpoint

Researchers observed fewer worsening heart failure events, but the trial did not establish a statistically significant benefit.

By
Kerri Miller
October 29, 2026
5 min

MDSpire News

At a Glance

Category	Detail
Condition	Clinical topic addressed by the source article: Digoxin Misses Heart Failure Endpoint
Key Mechanisms	Mechanisms or clinical associations described in the source article.
Target Population	Population described in the source article.
Care Setting	Randomized, double-blind, placebo-controlled trial of low-dose digoxin added to guideline-directed treatment in adults with symptomatic chronic heart failure.

Key Highlights

In the randomized DECISION trial of 1,001 patients, the primary composite of recurrent worsening heart failure events and cardiovascular mortality was not significantly reduced with low-dose digoxin versus placebo.
Over a median 36.5 months, primary outcome event rates were 15.7 per 100 patient-years with digoxin and 19.3 with placebo.
Cardiovascular mortality and all-cause mortality were similar between treatment groups.
Treatment-related serious adverse events occurred in 8% with digoxin and 5% with placebo; the difference was not statistically significant.
Exploratory subgroup and on-treatment analyses did not establish efficacy in a specific population or change the nonsignificant primary randomized comparison.

Guideline-Based Recommendations

Diagnosis

The trial enrolled patients with symptomatic chronic heart failure, elevated natriuretic peptide concentrations, and LVEF ≤50%; it did not evaluate diagnostic criteria.

Management

In DECISION, the primary composite endpoint was not significantly reduced when low-dose digoxin was added to contemporary guideline-directed treatment.
The trial regimen initiated digoxin at 0.1 or 0.2 mg daily according to age, renal function, and concomitant medications, targeting a serum concentration of 0.5–0.9 ng/mL.

Monitoring & Follow-up

In the trial, serum digoxin concentrations were measured 4 weeks after randomization and every 6 months thereafter, with dose adjustments guided by a central laboratory.
The median serum concentration was 0.6 ng/mL; 64% of patients with available 4-week measurements were within the target range.

Risks

Treatment-related serious adverse events were reported in 40 patients (8%) receiving digoxin and 25 (5%) receiving placebo; the difference was not statistically significant.
The study population was predominantly male and mostly NYHA class II, and treatment discontinuation was greater than anticipated; the authors identified these as limitations.

Patient & Prescribing Data

In the trial, low-dose digoxin was started at 0.1 or 0.2 mg daily based on age, renal function, and concomitant medications. The primary randomized comparison was not statistically significant; mortality was similar between groups.

Clinical Best Practices

The trial reported no statistically significant differences in treatment effects across 11 prespecified subgroups; subgroup findings were exploratory.
The exploratory on-treatment sensitivity analysis did not change the nonsignificant result of the primary randomized comparison.
At the end of follow-up, SGLT2 inhibitor use was 80% in the placebo group and 72% in the digoxin group; the authors noted this difference could have influenced the overall results.