Pharmacological treatment strategies to prevent heart failure across the cardiovascular-kidney-metabolic spectrum: an EJHF Expert Consensus Statement

Heart failure (HF) remains a major cause of morbidity, mortality, and increased healthcare costs worldwide, and is recognized as the result of progressive cardiovascular-kidney-metabolic (CKM) syndrome. Obesity, type 2 diabetes, chronic kidney disease, hypertension, and atherosclerotic cardiovascular disease frequently coexist and interact through shared pathophysiological mechanisms that promote HF onset, especially with preserved ejection fraction (HFpEF). This European Journal of Heart Failure (EJHF) Expert Consensus Statement synthesizes contemporary evidence supporting pharmacological strategies to prevent HF across the CKM spectrum. Foundational therapies, including renin-angiotensin system inhibitors, sodium-glucose cotransporter 2 inhibitors, non-steroidal mineralocorticoid receptor antagonists, and incretin-based agents, demonstrate complementary benefits in reducing HF events, cardiovascular death, and chronic kidney disease (CKD) progression in high-risk populations. Early, parallel initiation of these therapies may modify disease trajectory and attenuate progression from at-risk and pre-HF stages to overt clinical HF. This document further emphasizes the need for an up-front, accelerated implementation strategy supported by structured monitoring, multidisciplinary CKM care pathways, and proactive management of laboratory abnormalities. Overcoming barriers such as clinical inertia, safety misperceptions, polypharmacy, cost constraints, and inequities in access is essential to translate evidence into population-level impact. Harmonization of prevention frameworks across cardiology, nephrology, endocrinology, and primary care societies is urgently required. Integrated, cross-disciplinary implementation of evidence-based CKM management offers a realistic opportunity to reduce incident HF and mitigate its growing global burden.