Differences between men and women in guideline-directed medical therapy implementation, tolerability, and outcomes in HFrEF.
M I Wilde, L J Bouhuijzen, G P J Van Hout, M M De Leau, K W Wu, E A Van Beek, T Hesselink, L Kleijn, M J M Kurvers, R A Tio, C M Gijsberts, R A De Boer, H P Brunner-La Rocca, S Koudstaal, J J BrugtsAbstract
Background/Introduction
Guideline-directed medical therapy (GDMT) for heart failure with reduced ejection fraction (HFrEF) is well established, but data on differences between men and women in real-world implementation are limited.
Purpose
To examine whether men and women with HFrEF differ in GDMT use, tolerability, left ventricular ejection fraction (LVEF) changes, and clinical outcomes.
Methods
TITRATE-HF is a nationwide, prospective heart failure (HF) registry across 48 Dutch hospitals (June 2022-February 2024), enrolling patients with de novo, chronic, and worsening HF. The current analysis studied 3,367 HFrEF patients and compared men and women regarding GDMT use, dosing, titration, and side effects. LVEF changes were evaluated using serial echocardiography, and the composite endpoint (all-cause death or first HF hospitalization) was assessed with Kaplan–Meier analysis and adjusted Cox models.
Results
The cohort included 2,408 men (71.5%; 71 years [IQR 63-77]) and 959 women (28.5%; 72 years [IQR 64-79]). At 12 months, 59.0% of men and 59.7% of women received quadruple therapy (p= 0.729). Men more often achieved quadruple therapy at ≥50% of target doses (16.2% versus 11.9%, p= 0.004). Compared to men, women experienced more downgrades of ARB (11.6% versus 6.9%, p= 0.040) and MRA (13.2% versus 10.4%, p= 0.038) due to side effects or adverse reactions. In de novo HFrEF, women showed greater LVEF improvement than men (15% versus 13%, p= 0.005). In chronic HFrEF, women had lower risk of the composite endpoint compared to men (aHR 0.64, 95% CI 0.45–0.91; p= 0.014).
Conclusions
GDMT initiation and sequencing were similar in men and women, but men received higher doses. Despite higher doses, our findings indicate that men represent a higher-risk group in HFrEF, showing smaller LVEF improvement in de novo HFrEF and higher risk of worse outcome in chronic HFrEF. This underscores the need for implementation and dosing strategies accounting for differences between men and women.GDMT use men vs womenFor image description, please refer to the figure legend and surrounding text.Serial echo data men vs womenFor image description, please refer to the figure legend and surrounding text.