Digoxin and reduction in mortality and hospitalization in heart failure: a comprehensive post hoc analysis of the DIG trial - PubMed (original) (raw)

Randomized Controlled Trial

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

Ali Ahmed et al. Eur Heart J. 2006 Jan.

Abstract

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> or =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.

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Figures

Figure 1

Figure 1

Kaplan-Meier plots for cumulative risk of death due to all causes by serum digoxin concentration (SDC)

Figure 2

Figure 2

Kaplan-Meier plots for cumulative risk of death due to all causes among patients matched by propensity to develop serum digoxin concentrations (SDC) 0.5-0.9 ng/ml and ≥1.0 ng/ml

Figure 3

Figure 3

Kaplan-Meier plots for cumulative risk of hospitalization due to worsening heart failure (HF) by serum digoxin concentration (SDC)

Figure 4

Figure 4

Hazard ratio (95% confidence interval) for all-cause mortality in subgroups of patients with heart failure with serum digoxin concentration 0.5-0.9 ng/dL and placebo (ACE= angiotensin-converting enzyme, CKD= chronic kidney disease, EF= ejection fraction, NYHA= New York Heart Association)

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References

    1. Gheorghiade M, Adams KF, Jr, Colucci WS. Digoxin in the management of cardiovascular disorders. Circulation. 2004;109:2959–2964. - PubMed
    1. The Digitalis Investigation Group. The effect of digoxin on mortality and morbidity in patients with heart failure. N Engl J Med. 1997;336:525–533. - PubMed
    1. Hogg K, Swedberg K, McMurray J. Heart failure with preserved left ventricular systolic function; epidemiology, clinical characteristics, and prognosis. J Am Coll Cardiol. 2004;43:317–327. - PubMed
    1. Hunt SA, Baker DW, Chin MH, Cinquegrani MP, Feldman AM, Francis GS, Ganiats TG, Goldstein S, Gregoratos G, Jessup ML, Noble RJ, Packer M, Silver MA, Stevenson LW, Gibbons RJ, Antman EM, Alpert JS, Faxon DP, Fuster V, Jacobs AK, Hiratzka LF, Russell RO, Smith SC., Jr ACC/AHA Guidelines for the Evaluation and Management of Chronic Heart Failure in the Adult: Executive Summary A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Revise the 1995 Guidelines for the Evaluation and Management of Heart Failure): Developed in Collaboration With the International Society for Heart and Lung Transplantation; Endorsed by the Heart Failure Society of America. Circulation. 2001;104:2996–3007. - PubMed
    1. Smith TW, Butler VP, Jr, Haber E. Determination of therapeutic and toxic serum digoxin concentrations by radioimmunoassay. N Engl J Med. 1969;281:1212–1216. - PubMed

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