Research Progress on Pharmacotherapies for Heart Failure with Reduced Ejection Fraction

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Heart failure with reduced ejection fraction (HFrEF) is the subtype with the poorest prognosis within the heart failure spectrum, yet its treatment has witnessed groundbreaking advances in recent years. The “fourpillar” therapy based on neurohormonal inhibition—namely, angiotensin receptorneprilysin inhibitors (ARNI) / angiotensin receptor blockers (ARB), βblockers, mineralocorticoid receptor antagonists (MRA), and sodiumglucose cotransporter2 inhibitors (SGLT2i)—constitutes the cornerstone of guidelinedirected medical therapy (GDMT). However, the heterogeneity of HFrEF and persistently high rehospitalization rates indicate that, on top of existing therapies, novel drug development and precision treatment strategies targeting key pathophysiological processes—including myocardial energy metabolic reprogramming, inflammatory and immune dysregulation, and myocardial fibrosis—remain future priorities. This review aims to systematically outline the pathophysiological mechanisms of HFrEF, the clinical evidence and implementation strategies for currently available pharmacotherapies, and to discuss emerging drug targets (e.g., cardiac myosin modulators, antiinflammatory and metabolic regulators) as well as progress in traditional Chinese medicine research, with the goal of providing a reference for optimizing clinical management and guiding future investigations.

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