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

Gender-Based Differences in Heart Failure Hospitalizations Among Patients With Heart Failure With Reduced Ejection Fraction Treated With Spironolactone: A Prospective Cohort Study

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.

Study Overview

• Status: Completed
• Conditions: Heart Failure; Heart Failure NYHA Class II; Heart Failure NYHA Class III; Heart Failure With Reduced Ejection Fraction; Heart Failure NYHA Class IV
• Intervention / Treatment: Drug: Spironolactone

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 509

Contacts and Locations

Study Locations

• Saudi Arabia
  • Al 'Usaylah, Saudi Arabia
    • King Fahd Central Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

adult (≥ 18 years) ambulatory patients of both sexes with a diagnosis of HFrEF (LVEF≤ 40%) and NYHA class II-IV under optimized medical therapy who are presented to the outpatient clinic and started spironolactone at the time of enrollment.

Description

Inclusion Criteria:

• All adult (≥ 18 years) ambulatory patients of both sexes with a diagnosis of HFrEF (LVEF≤ 40%) and NYHA class II-IV under optimized medical therapy who are presented to the outpatient clinic and started spironolactone at the time of enrollment.

Exclusion Criteria:

• Pregnancy or breastfeeding
• Serum creatinine > 2.5 mg/dL (221 µmol/L) in males and > 2 mg/dL (177 µmol/L) in women (or estimated glomerular filtration rate (eGFR) ≤ 30 mL/minute/1.73 m2)
• Hyperkalemia (serum potassium level > 5 mEq/L)
• Renal transplantation
• Concomitant administration of potent CYP3A inhibitors
• Concomitant administration of potassium supplements or potassium-sparing diuretics
• Disorders of the adrenal glands (such as Addison disease).
• Patients who used MRA in the last 2 weeks before enrollment.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
The Female Group; Patients identified themselves as females (Apparent gender)	Drug: Spironolactone; All patients will receive Spironolactone as a part of their GDMT for Heart Failure
The Male Group; Patients identified themselves as males (Apparent gender)	Drug: Spironolactone; All patients will receive Spironolactone as a part of their GDMT for Heart Failure

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
HF Hospitalization	The event of hospitalization due to heart failure.	6 months after enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Hospitalization	The event of hospitalization due to any cause.	6 months after enrollment
All-cause mortality	The event of mortality due to any cause.	6 months after enrollment

Collaborators and Investigators

• Sponsor: Ahmad Abdullah Salawi

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2023
• Primary Completion (Actual): October 15, 2024
• Study Completion (Actual): October 15, 2024

Study Registration Dates

• First Submitted: October 11, 2024
• First Submitted That Met QC Criteria: October 11, 2024
• First Posted (Actual): October 15, 2024

Study Record Updates

• Last Update Posted (Actual): March 25, 2025
• Last Update Submitted That Met QC Criteria: March 19, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Heart Failure; Spironolactone; Gender
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure; Physiological Effects of Drugs; Hormones, Hormone Substitutes, and Hormone Antagonists; Hormone Antagonists; Diuretics; Natriuretic Agents; Mineralocorticoid Receptor Antagonists; Diuretics, Potassium Sparing; Spironolactone
• Other Study ID Numbers: 2460

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No