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Differences between men and women in guideline-directed medical therapy implementation, tolerability, and outcomes in

M I Wilde1, J J N Krabbe1, L J Bouhuijzen2

  • 1Erasmus MC, Cardiovascular Institute, Thorax Center, Department of Cardiology, Rotterdam, The Netherlands.

European Heart Journal. Quality of Care & Clinical Outcomes
|July 25, 2026
PubMed

Insights

Guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) shows similar initiation between men and women. However, women experienced more side effects, while showing improved ejection fraction and reduced mortality risk.

Area of Science:

  • Cardiology
  • Clinical Medicine
  • Pharmacology

Background:

  • Guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) is established.
  • Limited data exist on sex-based differences in real-world GDMT use, tolerability, and outcomes.

Purpose of the Study:

  • To examine sex-based differences in contemporary HFrEF patients.
  • To compare GDMT implementation, side effects, ejection fraction changes, and clinical outcomes between men and women with HFrEF.

Main Methods:

  • Prospective registry (TITRATE-HF) across 48 Dutch hospitals (June 2022-February 2024).
  • Analysis of 3,367 HFrEF patients (2,408 men, 959 women).
  • Comparison of GDMT (quadruple therapy) uptake, dose achievement, side effects, left ventricular ejection fraction (LVEF) changes, and composite clinical outcomes (HF hospitalization or all-cause death) at 12-month follow-up.

Main Results:

  • Quadruple therapy uptake was similar (59.0% men vs. 59.7% women).
  • Men more frequently achieved ≥50% of target GDMT doses (16.2% vs. 11.9%).
  • Women experienced more side effect-related downgrades for ARB (11.6% vs. 6.9%) and MRA (13.2% vs. 10.4%).
  • Women with de novo HFrEF showed greater LVEF improvement (15% vs. 13%).
  • Women with chronic HFrEF had a lower risk of composite endpoint (aHR 0.64).

Conclusions:

  • GDMT initiation and sequencing were comparable between sexes.
  • Differences exist in dose achievement, treatment tolerability, and clinical outcomes.
  • Implementation and dosing strategies should consider sex-specific differences in HFrEF management.
Abstract

Keywords:
Heart failureImplementationMenPharmacotherapyRegistryWomen

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