Digoxin and reduction in mortality and hospitalization in heart failure: a comprehensive post hoc analysis of the DIG trial

• Published in: European heart journal Vol. 27; no. 2; pp. 178 - 186
• Main Authors: Ahmed, Ali, Rich, Michael W., Love, Thomas E., Lloyd-Jones, Donald M., Aban, Inmaculada B., Colucci, Wilson S., Adams, Kirkwood F., Gheorghiade, Mihai
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01.01.2006; Oxford Publishing Limited (England)
• Subjects: Adrenergic beta-Antagonists - therapeutic use; Aged; Angiotensin-Converting Enzyme Inhibitors - therapeutic use; Biological and medical sciences; Cardiology. Vascular system; Cardiotonic Agents - therapeutic use; Chronic Disease; Diastolic heart failure; Digoxin; Digoxin - therapeutic use; Female; Follow-Up Studies; Heart; Heart failure; Heart Failure - drug therapy; Heart Failure - mortality; Heart failure, cardiogenic pulmonary edema, cardiac enlargement; Hospitalization; Hospitalization - statistics & numerical data; Humans; Male; Medical sciences; Middle Aged; Mortality; Preserved systolic function; Heart failure; Diastolic heart failure; Prognosis; Digoxin; Mortality; Cardiovascular disease; Hospitalization; Epidemiology; Phlebology; Reduction; Heart disease; Analysis; Preserved systolic function; Circulatory system; Cardiology
• ISSN: 0195-668X; 1522-9645
• DOI: 10.1093/eurheartj/ehi687

Aims To determine the effects of digoxin on all-cause mortality and heart failure (HF) hospitalizations, regardless of ejection fraction, accounting for serum digoxin concentration (SDC). Methods and results This comprehensive post-hoc analysis of the randomized controlled Digitalis Investigation Group trial (n=7788) focuses on 5548 patients: 1687 with SDC, drawn randomly at 1 month, and 3861 placebo patients, alive at 1 month. Overall, 33% died and 31% had HF hospitalizations during a 40-month median follow-up. Compared with placebo, SDC 0.5–0.9 ng/mL was associated with lower mortality [29 vs. 33% placebo; adjusted hazard ratio (AHR), 0.77; 95% confidence interval (CI), 0.67–0.89], all-cause hospitalizations (64 vs. 67% placebo; AHR, 0.85; 95% CI, 0.78–0.92) and HF hospitalizations (23 vs. 33% placebo; AHR, 0.62; 95% CI, 0.54–0.72). SDC≥1.0 ng/mL was associated with lower HF hospitalizations (29 vs. 33% placebo; AHR, 0.68; 95% CI, 0.59–0.79), without any effect on mortality. SDC 0.5–0.9 reduced mortality in a wide spectrum of HF patients and had no interaction with ejection fraction >45% (P=0.834) or sex (P=0.917). Conclusions Digoxin at SDC 0.5–0.9 ng/mL reduces mortality and hospitalizations in all HF patients, including those with preserved systolic function. At higher SDC, digoxin reduces HF hospitalization but has no effect on mortality or all-cause hospitalizations.