Variation in initial pharmacological therapy for heart failure with reduced ejection fraction: an international case-based survey

Background

Heart failure (HF) is associated with high morbidity and mortality and guideline-directed medical therapy (GDMT) improves outcomes in patients with HF with reduced ejection fraction (HFrEF). Current European Society of Cardiology guidelines strongly emphasize early initiation and rapid intensification of GDMT but do not specify which pharmacological class should be initiated first in individual patients.

As a result, health care professionals (HCPs) retain considerable discretion in prioritizing therapies at treatment initiation and uptitration. Accordingly, HCPs may favour certain pharmacological classes over others based on the patient’s clinical profile, their own clinical experience and local treatment protocols. To support this complex decision-making process, several expert consensus documents have proposed strategies for the initiation and uptitration of GDMT. Whether these recommendations are reflected in shared prioritization patterns in clinical practice remains unclear.

Purpose

The aim of this study was to describe the preferences and variation in initial pharmacological treatment choices for HFrEF across different HCPs. We hypothesized that these choices would converge on a limited number of preferred first-step therapies.

Methods

To describe variation in the initiation of pharmacological therapy in HFrEF, we conducted a web-based survey between January and November 2025 in which mainly European HCPs evaluated 12 treatment-naïve patient cases based on phenotypic profiles and selected an initial pharmacological treatment class per case. Variation in first-step treatment choices was described overall and across medical specialties.

Results

A total of 121 European HCPs participated, including 53 cardiologists in training (44%), 35 general cardiologists (29%), 14 HF cardiologists (12%), 8 HF nurses (7%), and 11 other specialists (9%). The 12 patient cases covered a broad range of clinical characteristics. Across cases, variation in initial pharmacological treatment choices was observed, with a mean of seven distinct medication classes selected as first-step therapy per case (standard deviation=1). In 7 cases (58%), sodium-glucose cotransporter-2 (SGLT2) inhibitors were the most frequently selected first-step therapy, followed by beta-blockers (25%) and angiotensin receptor-neprylisin inhibitors (ARNI, 17%). In three cases (25%) with low blood pressure, more than 50% of HCPs selected the same GDMT class. HF cardiologists more often selected the same class (>50% alignment within group) across cases than general cardiologists (67% vs. 8%).

Conclusion

Initial pharmacological treatment choices for HFrEF varied among HCPs. Greater alignment in initiation strategies may improve coordination of care and reduce delays in treatment.