Gender-based Differences in the Outcome of Treatment With Aldosterone Antagonists in Patients With Heart Failure (GBDAL-HF)

The Gender-Based Differences in the Outcome of Treatment by Aldosterone Antagonists in Patients With Heart Failure

Heart failure (HF) is a major healthcare problem. In patients with Heart Failure with Reduced Ejection Fraction (HFrEF), aldosterone antagonists reduce mortality and hospitalization rate. Gender-related differences have been described in the regulation of 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 RAAS.

In this single-center prospective cohort, a total of 100 adult (≥ 18 years) ambulatory patients of both sexes with the diagnosis of HF with HFrEF (LVEF≤ 40%) and NYHA class II-IV under optimized medical therapy started an aldosterone antagonist are enrolled and followed-up for 6 months. Patients are categorized according to their apparent sexual gender into two groups: the male group and the female group.

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: Potassium sparing diuretic

• Study Type: Observational
• Enrollment (Actual): 100

Contacts and Locations

Study Locations

• Egypt
  • Alexandria, Egypt
    • Faculty of Medicine, Alexandria University Hospitals

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Probability Sample

Study Population

New York Heart Association (NYHA) class II-IV heart failure with reduced ejection fraction HFrEF patients (LVEF≤ 40%).

Description

Inclusion Criteria:

• The diagnosis of heart failure with reduced ejection fraction HFrEF (LVEF≤ 40%) and New York Heart Association (NYHA) class II-IV under optimized medical therapy who are presented to the outpatient clinic and started an aldosterone antagonist at the time of enrollment.

Exclusion Criteria:

• Pregnancy or breast-feeding.
• 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 transplant.
• Concomitant administration of strong CYP3A inhibitors.
• Concomitant administration of potassium supplements or potassium-sparing diuretics.
• Disorders of adrenal glands (Addison disease).
• Patients who used mineralocorticoid receptor antagonists in the last 2 weeks before enrollment.
• Patients with a history of mineralocorticoid receptor antagonists allergy or intolerance.

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
The Female Group; Patients with an apparent gender of female.	Drug: Potassium sparing diuretic; Starting Spironolactone or Eplerenone at the time of enrollment.
The Male Group; Patients with an apparent gender of male.	Drug: Potassium sparing diuretic; Starting Spironolactone or Eplerenone at the time of enrollment.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Heart failure hospitalization	The incidence of Hospitalization due to heart failure	6 months after enrollment
Acute myocardial infarction	The incidence of acute myocardial infarction	6 months after enrollment
Percentage of patients who discontinued mineralocorticoid receptor antagonist	Discontinuation of mineralocorticoid receptor antagonist	6 months after enrollment
Switching from one mineralocorticoid receptor antagonist to another	Changing the mineralocorticoid receptor antagonist used	6 months after enrollment
Acute Kidney Injury	The incidence of acute kidney injury	6 months after enrollment
Adverse effects	The occurrence of Hyperkalemia, hypochloremic alkalosis, dehydration, or MRA adverse effects	6 months after enrollment

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
All-cause hospitalization rate	Hospitalization due to any cause including heart failure	6 months after enrollment
All-cause mortality rate	Death due to any cause	6 months after enrollment

Collaborators and Investigators

• Sponsor: Alexandria University
• Investigators: Principal Investigator: Salah Abdelkader, MSc, Cardiology Department, Faculty of Medicine, Alexandria University

Study record dates

Study Major Dates

• Study Start (Actual): October 15, 2022
• Primary Completion (Actual): July 15, 2023
• Study Completion (Actual): December 1, 2023

Study Registration Dates

• First Submitted: January 13, 2024
• First Submitted That Met QC Criteria: January 28, 2024
• First Posted (Actual): January 31, 2024

Study Record Updates

• Last Update Posted (Estimated): February 26, 2024
• Last Update Submitted That Met QC Criteria: February 23, 2024
• Last Verified: January 1, 2024

More Information

Terms related to this study

• Keywords: Heart Failure; Spironolactone; Hospitalization; Eplerenone; Heart Failure with Reduced Ejection Fraction; Gender
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Failure; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Sodium Channel Blockers; Diuretics, Potassium Sparing
• Other Study ID Numbers: GBDAL-HF Trial

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: Yes
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No