Gender-Based Differences in Heart Failure Hospitalizations Among Patients With Heart Failure Treated With Spironolactone

Overview

Aldosterone antagonists or mineralocorticoid receptor antagonists (MRAs) are used as therapeutic agents for the management of HF with reduced ejection fraction (HFrEF). Gender-related differences have been described in the regulation of the renin-angiotensin-aldosterone system (RAAS), which is at the core of the pathophysiology of HF. Regarding gender-related differences in the use of MRAs, less is known about the effects of androgens on the RAAS, even though studies have suggested that androgens may increase the RAAS pathway. There are conflicting results because many clinical trials were not specifically designed to investigate gender differences.

The RALES trial investigated the effect of spironolactone on symptomatic HF patients without any difference in treatment benefits between both genders. However, only 30 % of the patients enrolled were females. Another trial investigated the gender-based differences in the treatment of HFpEF patients with spironolactone. The results showed no significant sex differences in clinical endpoints, but a substantial reduction in all-cause mortality was associated with spironolactone use in females but not in males. The utilization of HF pharmacotherapy has been controversial, given recent discoveries presented by the PARAGON-HF trial.

Conditions