Mapping the Global Clinical Landscape of Pharmacological Therapies for Heart Failure With Preserved Ejection Fraction: An Analysis Based on ClinicalTrials.gov (2003–2025)

Heart failure with preserved ejection fraction (HFpEF) accounts for approximately 50% of global heart failure cases yet lacks robust pharmacological options. This analysis maps HFpEF drug trials registered on ClinicalTrials.gov from 2003 to 2025. A systematic search conducted on November 10, 2025, identified HFpEF‐specific drug trials (LVEF ≥ 50%). Data regarding geography, phases, status, time, and drug classes were descriptively analyzed using R (version 4.3.1). Of the 272 trials, 236 qualified, with a notable surge post‐2016 (180 [76.3%]). The majority were U.S.‐led (138 [58.5%]). Phase Ⅱ trials were predominant, comprising 92 trials (39.0%), with 111 trials completed (47.0%) and 36 trials terminated (15.2%). The leading classes of drugs included SGLT2 inhibitors (SGLT2i) and novel/targeted therapies, each represented in 31 trials (13.1%). The period from 2021 to 2025 highlighted a focus on SGLT2i (30 trials, or 27.8%) and an increase in GLP‐1 receptor agonists (GLP‐1RA), following recent approvals (sacubitril/valsartan in 2021; empagliflozin/dapagliflozin in 2022–2023; and finerenone by the FDA in 2025). The expansion of trials post‐2016 favors metabolic and targeted agents. However, attrition rates underscore the need to prioritize phenotype‐specific and combination trials.