Sex, digitalis, and the sodium pump.

Foxglove and its constituents therapeutic agent digitalis have been used for centuries for the treatment of heart failure. All digitalis-like cardiotonic steroids enhance heart contraction through a mechanism involving the inhibition of the Na(+),K(+)- ATPase. Recently, Rathore and colleagues reported that sex-based differences may exist in the efficacy of digoxin for the treatment of heart failure. The authors of the study found that female patients exhibited increased risk of death associated with digoxin therapy, whereas male patients appeared to have no increased risk of death related to digoxin therapy. Blaustein and colleagues delve into the report and discuss possible explanations for these findings, suggest alternative ones, and advocate for enrolling greater numbers of women in clinical studies.