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Association of serum digoxin concentration and outcomes in patients with heart failure.

Abstract

CONTEXT

The Digitalis Investigation Group (DIG) trial reported that digoxin provided no overall mortality benefit and only a modest reduction in hospitalizations among patients with heart failure and depressed left ventricular systolic function. The clinical outcomes associated with digoxin therapy at different serum concentrations in the DIG trial have not been assessed.

OBJECTIVE

To assess variations in serum digoxin concentration (SDC) and their association with mortality and hospitalization in patients with heart failure.

DESIGN, SETTING, AND PATIENTS

Post hoc analysis of the randomized, double-blinded, placebo-controlled DIG trial, conducted from August 1991 to December 1995, with the main analysis restricted to men with a left ventricular ejection fraction of 45% or less (n = 3782). Patients randomly assigned to receive digoxin were divided into 3 groups based on SDC at 1 month (0.5-0.8 ng/mL, n = 572; 0.9-1.1 ng/mL, n = 322; and > or =1.2 ng/mL, n = 277) and compared with patients randomly assigned to receive placebo (n = 2611).

MAIN OUTCOME MEASURE

All-cause mortality at a mean follow-up of 37 months.

RESULTS

Higher SDCs were associated with increased crude all-cause mortality rates (0.5-0.8 ng/mL, 29.9%; 0.9-1.1 ng/mL, 38.8%; and > or =1.2 ng/mL, 48.0%; P =.006 for trend). Patients with SDCs of 0.5 to 0.8 ng/mL had a 6.3% (95% confidence interval [CI], 2.1%-10.5%) lower mortality rate compared with patients receiving placebo. Digoxin was not associated with a reduction in mortality among patients with SDCs of 0.9 to 1.1 ng/mL (2.6% increase; 95% CI, - 3.0% to 8.3%), whereas patients with SDCs of 1.2 ng/mL and higher had an 11.8% (95% CI, 5.7%-18.0%) higher absolute mortality rate than patients receiving placebo. The association between SDC and mortality persisted after multivariable adjustment (SDC 0.5-0.8 ng/mL hazard ratio [HR] 0.80, 95% CI, 0.68-0.94; SDC 0.9-1.1 ng/mL HR 0.89, 95% CI, 0.74-1.08; SDC > or =1.2 ng/mL HR 1.16, 95% CI, 0.96-1.39; and HR of 1.00 [referent] for placebo).

CONCLUSIONS

Our findings demonstrate that higher SDCs were associated with increased mortality and suggest that the effectiveness of digoxin therapy in men with heart failure and a left ventricular ejection fraction of 45% or less may be optimized in the SDC range of 0.5 to 0.8 ng/mL.

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  • Publisher Full Text
  • Authors+Show Affiliations

    ,

    The Section of Cardiovascular Medicine, Yale University School of Medicine, New Haven, Conn 06520, USA.

    , , ,

    Source

    JAMA 289:7 2003 Feb 19 pg 871-8

    MeSH

    Cardiotonic Agents
    Data Interpretation, Statistical
    Digoxin
    Female
    Heart Failure
    Hospitalization
    Humans
    Male
    Middle Aged
    Survival Analysis
    Treatment Outcome
    Ventricular Dysfunction, Left

    Pub Type(s)

    Clinical Trial
    Journal Article
    Randomized Controlled Trial

    Language

    eng

    PubMed ID

    12588271

    Citation

    Rathore, Saif S., et al. "Association of Serum Digoxin Concentration and Outcomes in Patients With Heart Failure." JAMA, vol. 289, no. 7, 2003, pp. 871-8.
    Rathore SS, Curtis JP, Wang Y, et al. Association of serum digoxin concentration and outcomes in patients with heart failure. JAMA. 2003;289(7):871-8.
    Rathore, S. S., Curtis, J. P., Wang, Y., Bristow, M. R., & Krumholz, H. M. (2003). Association of serum digoxin concentration and outcomes in patients with heart failure. JAMA, 289(7), pp. 871-8.
    Rathore SS, et al. Association of Serum Digoxin Concentration and Outcomes in Patients With Heart Failure. JAMA. 2003 Feb 19;289(7):871-8. PubMed PMID: 12588271.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Association of serum digoxin concentration and outcomes in patients with heart failure. AU - Rathore,Saif S, AU - Curtis,Jeptha P, AU - Wang,Yongfei, AU - Bristow,Michael R, AU - Krumholz,Harlan M, PY - 2003/2/18/pubmed PY - 2003/2/28/medline PY - 2003/2/18/entrez SP - 871 EP - 8 JF - JAMA JO - JAMA VL - 289 IS - 7 N2 - CONTEXT: The Digitalis Investigation Group (DIG) trial reported that digoxin provided no overall mortality benefit and only a modest reduction in hospitalizations among patients with heart failure and depressed left ventricular systolic function. The clinical outcomes associated with digoxin therapy at different serum concentrations in the DIG trial have not been assessed. OBJECTIVE: To assess variations in serum digoxin concentration (SDC) and their association with mortality and hospitalization in patients with heart failure. DESIGN, SETTING, AND PATIENTS: Post hoc analysis of the randomized, double-blinded, placebo-controlled DIG trial, conducted from August 1991 to December 1995, with the main analysis restricted to men with a left ventricular ejection fraction of 45% or less (n = 3782). Patients randomly assigned to receive digoxin were divided into 3 groups based on SDC at 1 month (0.5-0.8 ng/mL, n = 572; 0.9-1.1 ng/mL, n = 322; and > or =1.2 ng/mL, n = 277) and compared with patients randomly assigned to receive placebo (n = 2611). MAIN OUTCOME MEASURE: All-cause mortality at a mean follow-up of 37 months. RESULTS: Higher SDCs were associated with increased crude all-cause mortality rates (0.5-0.8 ng/mL, 29.9%; 0.9-1.1 ng/mL, 38.8%; and > or =1.2 ng/mL, 48.0%; P =.006 for trend). Patients with SDCs of 0.5 to 0.8 ng/mL had a 6.3% (95% confidence interval [CI], 2.1%-10.5%) lower mortality rate compared with patients receiving placebo. Digoxin was not associated with a reduction in mortality among patients with SDCs of 0.9 to 1.1 ng/mL (2.6% increase; 95% CI, - 3.0% to 8.3%), whereas patients with SDCs of 1.2 ng/mL and higher had an 11.8% (95% CI, 5.7%-18.0%) higher absolute mortality rate than patients receiving placebo. The association between SDC and mortality persisted after multivariable adjustment (SDC 0.5-0.8 ng/mL hazard ratio [HR] 0.80, 95% CI, 0.68-0.94; SDC 0.9-1.1 ng/mL HR 0.89, 95% CI, 0.74-1.08; SDC > or =1.2 ng/mL HR 1.16, 95% CI, 0.96-1.39; and HR of 1.00 [referent] for placebo). CONCLUSIONS: Our findings demonstrate that higher SDCs were associated with increased mortality and suggest that the effectiveness of digoxin therapy in men with heart failure and a left ventricular ejection fraction of 45% or less may be optimized in the SDC range of 0.5 to 0.8 ng/mL. SN - 0098-7484 UR - https://www.unboundmedicine.com/medline/citation/12588271/full_citation L2 - https://jamanetwork.com/journals/jama/fullarticle/vol/289/pg/871 DB - PRIME DP - Unbound Medicine ER -