Journal Article
Koji Hasegawa,
Division of Translational Research, National Hospital Organization Kyoto Medical Center
, 1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto 612-8555,
Japan
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Basil S LewisRuth and Bruce Rappaport School of Medicine, Technion—Israel Institute of Technology
,
Israel
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Received:
16 January 2022
Published:
28 January 2022
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Koji Hasegawa, Basil S Lewis, Are SGLT2 inhibitors effective against ‘all’ heart failure with preserved ejection fraction?, European Heart Journal - Cardiovascular Pharmacotherapy, Volume 8, Issue 3, May 2022, Page E10, //doi.org/10.1093/ehjcvp/pvac004
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The European Society of Cardiology’s (ESC) guidelines on heart failure were revised for the first time in five years and presented at an online ESC conference held from 27 August to 30 August 2021.1 Renin–angiotensin system inhibitors, beta-blockers, mineralocorticoid receptor antagonists, and sodium–glucose cotransporter-2 (SGLT2) inhibitors are the mainstays of treatment for heart failure with reduced left ventricular ejection fraction (HFrEF), and are collectively known as the ‘fantastic four’. However, effective drug therapies have not been established for heart failure with preserved ejection fraction (HFpEF). Yet the EMPEROR-Preserved trial, which was also presented at the ESC 2021 conference, showed that the SGLT2 inhibitor empagliflozin was effective for adult patients with chronic heart failure having New York Heart Association class II–IV symptoms and EF ≥40%.2 The initial event incidence of the primary endpoint—cardiovascular death or hospitalization for heart failure—was 13.8% in the SGLT2 inhibitor empagliflozin group and 17.1% in the placebo group, and the risk was significantly reduced by 21% in the empagliflozin group (95% confidence interval 0.69–0.90, P = 0.0003).
The results of further precise analyses stratified by EF have also been reported for the EMPEROR-Preserved trial.2 For all heart failure hospitalizations, the hazard ratios for the empagliflozin group with respect to the placebo group for patients with EF 40–50%, EF 50–60%, and EF ≥60% were 0.57, 0.66, and 1.06, respectively, which shows that EF affected outcomes, with lower EF associated with better outcomes (P = 0.008). Thus, empagliflozin prevented heart failure hospitalization in heart failure with mildly reduced ejection fraction at 40–49% (HFmrEF) and HFpEF with slightly reduced ejection fraction (EF 50–60%), but it did not prevent hospitalization when EF was normal (EF ≥60%).
The PARAGON-HF trial, which examined the efficacy of sacubitril/valsartan for HFpEF patients, also reported that the preventive effect on heart failure hospitalization weakens when EF is high.3 The EMPEROR-Preserved trial shows that when EF <60%, empagliflozin is a beneficial drug for HFpEF, for which there is a dearth of effective therapeutic agents. Unfortunately, there is still no established strategy for HFpEF when EF is normal (≥60%), and the number of such patients is expected to increase as society ages. This is an issue that needs to be further investigated and resolved. As HFpEF involves a complex pathology, it may be necessary to stratify patients according to a variety of characteristics to examine which drugs should be selected for each population.
Conflict of interest: None declared.
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© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.
© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.
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