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Effectiveness of digoxin in reducing one-year mortality in chronic heart failure in the Digitalis Investigation Group trial.
Am J Cardiol 2009; 103(1):82-7AJ

Abstract

Post hoc analyses of the Digitalis Investigation Group (DIG) trial indicate that digoxin at low (0.5 to 0.9 ng/ml) serum digoxin concentration (SDC) reduces mortality, which is eliminated at higher (>or=1 ng/ml) SDC, and that low-dose digoxin (<or=0.125 mg/day) predicts low SDC. In the DIG trial, patients with ambulatory chronic systolic and diastolic heart failure (HF) (n = 7,788) in normal sinus rhythm receiving angiotensin-converting enzyme inhibitors and diuretics were randomized to receive placebo (n = 3,899) or digoxin (n = 3,889). The median dose of digoxin (0.25 mg/day) and the target SDC (0.8 to 2.5 ng/ml) were higher than what are currently recommended, which in part may explain the lack of long-term mortality benefit of digoxin in the DIG trial. To test this hypothesis, we examined the effect of digoxin on short-term outcomes; 1-year all-cause mortality occurred in 392 and 448 patients respectively in the digoxin and placebo groups (hazard ratio for digoxin 0.87, 95% confidence interval [CI] 0.76 to 0.995, p = 0.043). Respective hazard ratios for cardiovascular and HF deaths were 0.87 (95% CI 0.76 to 1.01, p = 0.072) and 0.66 (95% CI 0.52 to 0.85, p = 0.001). All-cause hospitalization occurred in 1,411 and 1,529 patients receiving digoxin and placebo respectively (hazard ratio 0.89, 95% CI 0.83 to 0.96, p = 0.002). Respective hazard ratios for cardiovascular and HF hospitalizations were 0.82 (95% CI 0.75 to 0.89, p <0.0001) and 0.59 (95% CI 0.52 to 0.66, p <0.0001). In conclusion, digoxin reduced 1-year mortality and hospitalization in patients with chronic HF receiving angiotensin-converting enzyme inhibitors and diuretics. Randomized clinical trials are needed to determine the effect of low-dose digoxin in contemporary patients with chronic HF.

Authors+Show Affiliations

University of Alabama at Birmingham, Birmingham, Alabama, USA. aahmed@uab.eduNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Comparative Study
Journal Article
Multicenter Study
Randomized Controlled Trial
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

19101235

Citation

Digitalis Investigation Group, et al. "Effectiveness of Digoxin in Reducing One-year Mortality in Chronic Heart Failure in the Digitalis Investigation Group Trial." The American Journal of Cardiology, vol. 103, no. 1, 2009, pp. 82-7.
Digitalis Investigation Group, Ahmed A, Waagstein F, et al. Effectiveness of digoxin in reducing one-year mortality in chronic heart failure in the Digitalis Investigation Group trial. Am J Cardiol. 2009;103(1):82-7.
Ahmed, A., Waagstein, F., Pitt, B., White, M., Zannad, F., Young, J. B., & Rahimtoola, S. H. (2009). Effectiveness of digoxin in reducing one-year mortality in chronic heart failure in the Digitalis Investigation Group trial. The American Journal of Cardiology, 103(1), pp. 82-7. doi:10.1016/j.amjcard.2008.06.068.
Digitalis Investigation Group, et al. Effectiveness of Digoxin in Reducing One-year Mortality in Chronic Heart Failure in the Digitalis Investigation Group Trial. Am J Cardiol. 2009 Jan 1;103(1):82-7. PubMed PMID: 19101235.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effectiveness of digoxin in reducing one-year mortality in chronic heart failure in the Digitalis Investigation Group trial. AU - ,, AU - Ahmed,Ali, AU - Waagstein,Finn, AU - Pitt,Bertram, AU - White,Michel, AU - Zannad,Faiez, AU - Young,James B, AU - Rahimtoola,Shahbudin H, Y1 - 2008/10/23/ PY - 2008/05/12/received PY - 2008/06/06/revised PY - 2008/06/06/accepted PY - 2008/12/23/entrez PY - 2008/12/23/pubmed PY - 2009/1/14/medline SP - 82 EP - 7 JF - The American journal of cardiology JO - Am. J. Cardiol. VL - 103 IS - 1 N2 - Post hoc analyses of the Digitalis Investigation Group (DIG) trial indicate that digoxin at low (0.5 to 0.9 ng/ml) serum digoxin concentration (SDC) reduces mortality, which is eliminated at higher (>or=1 ng/ml) SDC, and that low-dose digoxin (<or=0.125 mg/day) predicts low SDC. In the DIG trial, patients with ambulatory chronic systolic and diastolic heart failure (HF) (n = 7,788) in normal sinus rhythm receiving angiotensin-converting enzyme inhibitors and diuretics were randomized to receive placebo (n = 3,899) or digoxin (n = 3,889). The median dose of digoxin (0.25 mg/day) and the target SDC (0.8 to 2.5 ng/ml) were higher than what are currently recommended, which in part may explain the lack of long-term mortality benefit of digoxin in the DIG trial. To test this hypothesis, we examined the effect of digoxin on short-term outcomes; 1-year all-cause mortality occurred in 392 and 448 patients respectively in the digoxin and placebo groups (hazard ratio for digoxin 0.87, 95% confidence interval [CI] 0.76 to 0.995, p = 0.043). Respective hazard ratios for cardiovascular and HF deaths were 0.87 (95% CI 0.76 to 1.01, p = 0.072) and 0.66 (95% CI 0.52 to 0.85, p = 0.001). All-cause hospitalization occurred in 1,411 and 1,529 patients receiving digoxin and placebo respectively (hazard ratio 0.89, 95% CI 0.83 to 0.96, p = 0.002). Respective hazard ratios for cardiovascular and HF hospitalizations were 0.82 (95% CI 0.75 to 0.89, p <0.0001) and 0.59 (95% CI 0.52 to 0.66, p <0.0001). In conclusion, digoxin reduced 1-year mortality and hospitalization in patients with chronic HF receiving angiotensin-converting enzyme inhibitors and diuretics. Randomized clinical trials are needed to determine the effect of low-dose digoxin in contemporary patients with chronic HF. SN - 1879-1913 UR - https://www.unboundmedicine.com/medline/citation/19101235/Effectiveness_of_digoxin_in_reducing_one_year_mortality_in_chronic_heart_failure_in_the_Digitalis_Investigation_Group_trial_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0002-9149(08)01450-1 DB - PRIME DP - Unbound Medicine ER -