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Evevident
Original paper
1997NEJMCardiology

DIG

The effect of digoxin on mortality and morbidity in patients with heart failure

RCTHFrEF

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Overview

Digoxin reduced HF hospitalizations but did not improve survival in heart failure.

Clinical takeaway

DIG explains digoxin's modern niche: symptom and hospitalization reduction in selected HFrEF patients, not mortality benefit.

Key result

All-cause mortality was neutral, while hospitalizations for worsening HF were reduced.

Practice impact

Digoxin became an adjunct for selected symptomatic patients rather than a foundational survival drug.

Evidence

Study design

Randomized, double-blind, placebo-controlled trial.

Enrollment

6,800

Follow-up

Mean 37 months.

Geography

United States, Canada

Clinical question

Does digoxin reduce mortality or hospitalization in patients with heart failure in sinus rhythm?

Population

  • Patients with heart failure and normal sinus rhythm, most with reduced ejection fraction, receiving diuretics and ACE inhibitors.

Intervention

Digoxin.

Comparator

Placebo.

Primary outcome

All-cause mortality.

Digoxin did not reduce all-cause mortality but reduced heart-failure hospitalization.

Relative risk / 0.99 / CI 95% CI 0.91-1.07 / p=0.80

Key results

  • All-cause mortality did not differ significantly.
  • Hospitalization for worsening heart failure was reduced.
  • Narrow therapeutic index and renal dosing remain central to safe use.

Harms

  • Digoxin toxicity can cause arrhythmias, GI symptoms, confusion, and visual changes.
  • Risk increases with kidney dysfunction, hypokalemia, and interacting drugs.

Clinical Use

When to cite

  • When explaining why digoxin may reduce HF admissions but not mortality.

Practice impact

  • Clarified that digoxin is not a mortality-improving HFrEF therapy.

Applicability

  • Selected symptomatic HFrEF patients despite GDMT or patients needing additional rate control where appropriate.

Limitations

  • Pre-contemporary GDMT and studied sinus rhythm for the main trial question.
  • Serum concentration targets in modern practice are lower than historic dosing habits.

Common misinterpretations

  • Do not cite DIG as support for digoxin as a first-line HFrEF survival medication.

Related evidence

DECISION - Later TrialSOLVD Treatment - Same DiseaseRALES - Same Disease

Citation

Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med. 1997;336(8):525-533. doi:10.1056/NEJM199702203360801