DIG
Trial question
What is the role of digoxin in patients with a LVEF ≤ 0.45 being treated with diuretics and ACE inhibitors?
Study design
Multi-center
Double blinded
RCT
Population
Characteristics of study participants
22.0% female
78.0% male
N = 6800
6800 patients (1520 female, 5280 male).
Inclusion criteria: patients with an LVEF ≤ 0.45 being treated with diuretics and ACE inhibitors.
Key exclusion criteria: age < 21 years, MI or cardiac surgery within 4 weeks, unstable or refractory angina < 1 month, acute myocarditis, HCM, cor pulmonale, or complex congenital heart disease.
Interventions
N=3397 digoxin (0.25 mg/day).
N=3403 placebo (matching placebo per day).
Primary outcome
All-cause mortality
34.8%
35.1%
35.1 %
26.3 %
17.6 %
8.8 %
0.0 %
Digoxin
Placebo
No significant
difference ↔
No significant difference in all-cause mortality (34.8% vs. 35.1%; RR 0.99, 99% CI 0.91 to 1.07).
Secondary outcomes
Significant decrease in hospitalization for worsening HF (26.8% vs. 34.7%; RR 0.72, 95% CI 0.66 to 0.79).
No significant difference in death attributed to worsening HF (11.6% vs. 13.2%; RR 0.88, 95% CI 0.77 to 1.01).
No significant difference in CV death (29.9% vs. 29.5%; RR 1.01, 95% CI 0.93 to 1.1).
Safety outcomes
No significant difference in VF or tachycardia.
Significant differences in digoxin toxicity (11.9% vs. 7.9%), supraventricular arrhythmia (2.5% vs. 1.2%) and second or third degree AV block (1.2% vs. 0.4%).
Conclusion
In patients with an LVEF ≤ 0.45 being treated with diuretics and ACE inhibitors, digoxin was not superior to placebo with respect to all-cause mortality.
Reference
Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med. 1997 Feb 20;336(8):525-33.
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