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Sex-based differences in the effect of digoxin for the treatment of heart failure.
N Engl J Med 2002; 347(18):1403-11NEJM

Abstract

BACKGROUND

The Digitalis Investigation Group trial reported that treatment with digoxin did not decrease overall mortality among patients with heart failure and depressed left ventricular systolic function, although it did reduce hospitalizations slightly. Even though the epidemiologic features, causes, and prognosis of heart failure vary between men and women, sex-based differences in the effect of digoxin were not evaluated.

METHODS

We conducted a post hoc subgroup analysis to assess whether there were sex-based differences in the effect of digoxin therapy among the 6800 patients in the Digitalis Investigation Group study. The presence of an interaction between sex and digoxin therapy with respect to the primary end point of death from any cause was evaluated with the use of Mantel-Haenszel tests of heterogeneity and a multivariable Cox proportional-hazards model, adjusted for demographic and clinical variables.

RESULTS

There was an absolute difference of 5.8 percent (95 percent confidence interval, 0.5 to 11.1) between men and women in the effect of digoxin on the rate of death from any cause (P=0.034 for the interaction). Specifically, women who were randomly assigned to digoxin had a higher rate of death than women who were randomly assigned to placebo (33.1 percent vs. 28.9 percent; absolute difference, 4.2 percent, 95 percent confidence interval, -0.5 to 8.8). In contrast, the rate of death was similar among men randomly assigned to digoxin and men randomly assigned to placebo (35.2 percent vs. 36.9 percent; absolute difference, -1.6 percent; 95 percent confidence interval, -4.2 to 1.0). In the multivariable analysis, digoxin was associated with a significantly higher risk of death among women (adjusted hazard ratio for the comparison with placebo, 1.23; 95 percent confidence interval, 1.02 to 1.47), but it had no significant effect among men (adjusted hazard ratio, 0.93; 95 percent confidence interval, 0.85 to 1.02; P=0.014 for the interaction).

CONCLUSIONS

The effect of digoxin therapy differs between men and women. Digoxin therapy is associated with an increased risk of death from any cause among women, but not men, with heart failure and depressed left ventricular systolic function.

Authors+Show Affiliations

Section of Cardiovascular Medicine, Department of Internal Medicine, Yale-New Haven Hospital, New Haven, Conn, USA.No affiliation info availableNo affiliation info available

Pub Type(s)

Clinical Trial
Journal Article
Randomized Controlled Trial
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

12409542

Citation

Rathore, Saif S., et al. "Sex-based Differences in the Effect of Digoxin for the Treatment of Heart Failure." The New England Journal of Medicine, vol. 347, no. 18, 2002, pp. 1403-11.
Rathore SS, Wang Y, Krumholz HM. Sex-based differences in the effect of digoxin for the treatment of heart failure. N Engl J Med. 2002;347(18):1403-11.
Rathore, S. S., Wang, Y., & Krumholz, H. M. (2002). Sex-based differences in the effect of digoxin for the treatment of heart failure. The New England Journal of Medicine, 347(18), pp. 1403-11.
Rathore SS, Wang Y, Krumholz HM. Sex-based Differences in the Effect of Digoxin for the Treatment of Heart Failure. N Engl J Med. 2002 Oct 31;347(18):1403-11. PubMed PMID: 12409542.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Sex-based differences in the effect of digoxin for the treatment of heart failure. AU - Rathore,Saif S, AU - Wang,Yongfei, AU - Krumholz,Harlan M, PY - 2002/11/1/pubmed PY - 2002/11/26/medline PY - 2002/11/1/entrez SP - 1403 EP - 11 JF - The New England journal of medicine JO - N. Engl. J. Med. VL - 347 IS - 18 N2 - BACKGROUND: The Digitalis Investigation Group trial reported that treatment with digoxin did not decrease overall mortality among patients with heart failure and depressed left ventricular systolic function, although it did reduce hospitalizations slightly. Even though the epidemiologic features, causes, and prognosis of heart failure vary between men and women, sex-based differences in the effect of digoxin were not evaluated. METHODS: We conducted a post hoc subgroup analysis to assess whether there were sex-based differences in the effect of digoxin therapy among the 6800 patients in the Digitalis Investigation Group study. The presence of an interaction between sex and digoxin therapy with respect to the primary end point of death from any cause was evaluated with the use of Mantel-Haenszel tests of heterogeneity and a multivariable Cox proportional-hazards model, adjusted for demographic and clinical variables. RESULTS: There was an absolute difference of 5.8 percent (95 percent confidence interval, 0.5 to 11.1) between men and women in the effect of digoxin on the rate of death from any cause (P=0.034 for the interaction). Specifically, women who were randomly assigned to digoxin had a higher rate of death than women who were randomly assigned to placebo (33.1 percent vs. 28.9 percent; absolute difference, 4.2 percent, 95 percent confidence interval, -0.5 to 8.8). In contrast, the rate of death was similar among men randomly assigned to digoxin and men randomly assigned to placebo (35.2 percent vs. 36.9 percent; absolute difference, -1.6 percent; 95 percent confidence interval, -4.2 to 1.0). In the multivariable analysis, digoxin was associated with a significantly higher risk of death among women (adjusted hazard ratio for the comparison with placebo, 1.23; 95 percent confidence interval, 1.02 to 1.47), but it had no significant effect among men (adjusted hazard ratio, 0.93; 95 percent confidence interval, 0.85 to 1.02; P=0.014 for the interaction). CONCLUSIONS: The effect of digoxin therapy differs between men and women. Digoxin therapy is associated with an increased risk of death from any cause among women, but not men, with heart failure and depressed left ventricular systolic function. SN - 1533-4406 UR - https://www.unboundmedicine.com/medline/citation/12409542/Sex_based_differences_in_the_effect_of_digoxin_for_the_treatment_of_heart_failure_ L2 - http://www.nejm.org/doi/full/10.1056/NEJMoa021266?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -