Sex differences in heart failure medications targeting the renin-angiotensin-aldosterone system

Abstract

Heart failure (HF) is a major healthcare problem. Sex-related differences in clinical manifestations, outcomes, risk factors and symptoms in HF have been described in the literature. Sex-related differences have also been described in the regulation of the renin-angiotensin-aldosterone system (RAAS), which is at the core of the pathophysiology of HF. Considering that drugs targeting RAAS are cornerstones in the treatment of HF, it is important to determine whether sex-related differences exist in the use of angiotensin converting enzyme inhibitors (ACEIs), angiotensin receptor blockers (ARBs), mineralocorticoid receptor antagonists (MRAs) and ARB/neprilysin inhibitors (ARNIs). In regards to the relative efficacy of RAAS drugs in men vs. women in HF, there are conflicting results, which may stem from the fact that a lot of clinical trials were not specifically designed to investigate sex differences, with many of them having an underrepresentation of women. With respect to optimal dosage of RAAS drugs, even though, current HF guidelines, recommend up-titration to the same target dose in both men and women, evidence suggests that lower doses could be used in women. Furthermore, several studies have reported underutilization of guideline-directed medical therapy in women, including ACEIs, ARBs and MRAs, which may be at least partially attributed to increased prevalence of HF with a preserved ejection fraction and increased propensity for adverse effects in women. Overall, these investigations have shed some light on sex-related differences but there is scope for conducting further studies to determine the optimal use of RAAS drugs in men and women with failing hearts.

Keywords: Aldosterone antagonist; Angiotensin converting enzyme inhibitor; Angiotensin receptor blocker; Heart failure; Renin-angiotensin-aldosterone system; Sex differences.