Clinical Scorecard: DECISION: Digoxin Did Not Significantly Reduce the Primary Heart Failure Endpoint

At a Glance

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.

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