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Sex differences in mineralocorticoid receptor antagonist trials : A pooled analysis of three large clinical trials
Rossello, Xavier Ferreira, João Pedro Pocock, Stuart J. McMurray, John J. V. Solomon, Scott D. Lam, Carolyn S. P. Girerd, Nicolas Pitt, Bertram Rossignol, Patrick Zannad, Faiez
Rossello, Xavier
Ferreira, João Pedro
Pocock, Stuart J.
McMurray, John J. V.
Solomon, Scott D.
Lam, Carolyn S. P.
Girerd, Nicolas
Pitt, Bertram
Rossignol, Patrick
Zannad, Faiez
Abstract
Aims
Women with heart failure (HF) are under‐represented in individual randomized clinical trials (RCTs). Little is known about sex‐specific treatment effects in HF medications. We evaluated sex differences in the response to mineralocorticoid receptor antagonists (MRAs) in major HF MRA trials, including a broad spectrum of left ventricular ejection fraction (LVEF).
Methods and results
Individual patient data fixed‐effect meta‐analysis was performed using 6167 patients (31.4% were women) recruited in three placebo‐controlled RCTs: Randomized Aldactone Evaluation Study (RALES), Eplerenone in Mild Patients Hospitalization and Survival Study in Heart Failure (EMPHASIS‐HF) and Spironolactone for Heart Failure with Preserved Ejection Fraction (TOPCAT)‐Americas. Compared to men, women were older, had higher body mass index and lower glomerular filtration rate. They also had higher LVEF and poorer New York Heart Association functional class and were less likely to be taking angiotensin‐converting enzyme inhibitors/angiotensin II receptor blockers. Placebo‐arm event rates were lower for women compared with men (15.4 vs. 22.1 per 100 person‐year; P = 0.002). MRAs reduced consistently, in men and women, the relative risk for cardiovascular death or HF hospitalization (P for interaction = 0.83), cardiovascular death (P for interaction = 0.44) and all‐cause death (P for interaction = 0.19). These findings remained consistent after adjustment for potential confounders, regardless of LVEF. There was no sex‐specific impact of MRA on the rate of hyperkalaemia and worsening renal function during the median 22 months of follow‐up.
Conclusion
In three large MRA RCTs, women were substantially different from men with regard to their clinical features and event rates. Nonetheless, this meta‐analysis supports a consistent and beneficial MRA effect regardless of sex.
Keywords
heart failure, mineralocorticoid receptor antagonists, meta-analysis, women
Date
2020
Type
Journal article
Journal
European Journal of Heart Failure
Book
Volume
22
Issue
5
Page Range
834-844
Article Number
ACU Department
Collections
Relation URI
Source URL
Event URL
Open Access Status
License
All rights reserved
File Access
Controlled