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Empagliflozin: A Review in Symptomatic Chronic Heart Failure

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Abstract

Empagliflozin (Jardiance®), a sodium-glucose cotransporter 2 inhibitor (SGLT2i) initially developed to treat type 2 diabetes mellitus (T2DM), has also been approved in the EU and USA for the treatment of all adults with symptomatic chronic heart failure (CHF), regardless of their left ventricular ejection fraction (LVEF). In pivotal phase III trials in ambulant patients with symptomatic CHF and mildly-reduced or preserved ejection fraction (EMPEROR-Preserved; LVEF > 40%) or those with symptomatic CHF and reduced ejection fraction (EMPEROR–Reduced; LVEF ≤ 40%), the addition of oral empagliflozin 10 mg/day to standard of care significantly reduced the risk of cardiovascular (CV) death or hospitalization for HF (HHF), as well as that of a number of other outcomes indicative of worsening HF, compared with placebo. The beneficial effect of empagliflozin on CV death/HHF was seen irrespective of the presence or absence of T2DM and regardless of background HF therapies. In addition, empagliflozin significantly improved health-related quality of life (HRQOL) and was generally well tolerated, with an adverse event profile that was generally consistent with that seen in patients with T2DM. Thus, empagliflozin is a valuable treatment option for ambulant patients with symptomatic CHF across a broad LVEF spectrum.

Plain Language Summary

Categorizing chronic heart failure (CHF) according to left ventricular ejection fraction (LVEF) is central to the management of this condition. CHF with a reduced ejection fraction (HFrEF) is characterized by a LVEF ≤ 40%; CHF with a mildly reduced ejection fraction (HFmrEF) is characterized by a LVEF of 41–49%; and CHF with a preserved ejection fraction (HFpEF) is characterized by a LVEF of ≥ 50%. Historically, standard of care treatments for HFrEF have not been effective against HFpEF, which is becoming the most common form of HF. Empagliflozin (Jardiance®) is the first sodium-glucose cotransporter type 2 inhibitor to be approved for the treatment of adults with symptomatic CHF, regardless of their LVEF. Empagliflozin significantly reduced the risk of hospitalization for HF or cardiovascular death in nonhospitalized patients with HFpEF, HFmrEF or HFrEF, regardless of diabetes status and the standard HF therapies they were already taking. Empagliflozin also improved health-related quality of life and was generally well tolerated. Empagliflozin is a valuable treatment option for patients with symptomatic CHF associated with a broad range of LVEFs.

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Acknowledgments

During the peer review process, the manufacturer of empagliflozin was also offered an opportunity to review this article. Changes resulting from comments received were made on the basis of scientific and editorial merit.

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James E. Frampton is a salaried employee6 of Adis International Ltd/Springer Nature, and declares no relevant conflicts of interest. All authors contributed to the review and are responsible for the article content.

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The manuscript was reviewed by: M. M. Y. Lee, School of Cardiovascular & Metabolic Health, University of Glasgow, UK; B. Pitt, Department of Internal Medicine, Division of Cardiology, University of Michigan School of Medicine, Ann Arbor, MI, USA; J.-Y. Sun, Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

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Frampton, J.E. Empagliflozin: A Review in Symptomatic Chronic Heart Failure. Drugs 82, 1591–1602 (2022). https://doi.org/10.1007/s40265-022-01778-0

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