Pharmacological Management of Heart Failure with Reduced Ejection Fraction
Summary
Heart failure with reduced ejection fraction (HFrEF) remains a leading cause of morbidity and mortality worldwide. Pharmacological management has evolved into a four-pillar strategy encompassing inhibitors of maladaptive neurohormonal pathways and metabolic modulators. First-line agents include angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers, and more recently angiotensin receptor–neprilysin inhibitors, which attenuate the renin-angiotensin-aldosterone system and augment natriuretic peptides. Beta-blockers counteract sympathetic overactivity, improving myocardial remodelling and survival. Mineralocorticoid receptor antagonists further suppress aldosterone-mediated fibrosis and arrhythmic risk. The advent of sodium-glucose cotransporter 2 inhibitors has added a glucose-independent mechanism that promotes diuresis, reduces preload and afterload, and improves renal function. Optimal benefit derives from early implementation of all four classes, with rapid up-titration to target or maximally tolerated doses. Despite clear guideline recommendations, real-world uptake remains suboptimal, owing to clinical inertia, comorbidity, healthcare infrastructure and concerns about hypotension or renal dysfunction. Precision in patient stratification, tailored sequencing of therapies and integrated care pathways are key to maximising survival, reducing hospitalisation and improving quality of life.
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Pharmacological Management of Heart Failure with Reduced Ejection Fraction publication trend
The graph below shows the total number of articles in pharmacological management of heart failure with reduced ejection fraction across all publications each year (not limited to Nature Index journals).
Technical terms
Heart failure with reduced ejection fraction (HFrEF): A clinical syndrome in which the heart’s left ventricle ejects less than 40–50% of blood per beat.
Guideline-directed medical therapy (GDMT): Evidence-based pharmacological regimen recommended by professional societies to improve outcomes in HFrEF.
Angiotensin receptor–neprilysin inhibitor (ARNI): A combined agent that inhibits angiotensin II receptors and neprilysin, enhancing natriuretic peptide levels.
Sodium-glucose cotransporter 2 inhibitor (SGLT2i): Originally an antidiabetic class, now shown to reduce heart failure events by promoting osmotic diuresis and modulating cardiac metabolism.
Mineralocorticoid receptor antagonist (MRA): A drug that blocks aldosterone receptors, reducing sodium retention, fibrosis and arrhythmia risk.
References
- Four pillars of heart failure: contemporary pharmacological therapy for heart failure with reduced ejection fraction. Open Heart (2021).
- Clinical inertia in the treatment of heart failure: a major issue to tackle. Heart Failure Reviews (2020).
- Eligibility and Projected Benefits of Rapid Initiation of Quadruple Therapy for Newly Diagnosed Heart Failure. JACC Heart Failure (2024).
- Guideline-directed medical therapy for HFrEF: sequencing strategies and barriers for life-saving drug therapy. Heart Failure Reviews (2023).
- Network meta‐analysis of medical therapy efficacy in more than 90,000 patients with heart failure and reduced ejection fraction. Journal of Internal Medicine (2022).
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