Sex-Based Differences in the Effect of Digoxin for the Treatment of Heart Failure
New England Journal of MedicinePublished 30 October 2002
Saif S. Rathore, Yongfei Wang, Harlan M. Krumholz
Citations682
SJR quartileQ1
SJR score19.08
SNIP13.47
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TL;DR
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.
Abstract
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.
Keywords
Medicine
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