Journal Article Show Koji Hasegawa, Division of Translational Research, National Hospital Organization Kyoto Medical Center , 1-1 Mukaihata-cho, Fukakusa, Fushimi-ku, Kyoto 612-8555, Japan Search for other works by this author on: Basil S LewisRuth and Bruce Rappaport School of Medicine, Technion—Israel Institute of Technology , Israel Search for other works by this author on: Received: 16 January 2022 Published: 28 January 2022
Close Navbar Search Filter Microsite Search Term Search 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. References1. McDonagh TA ,Metra M ,Adamo M ,Gardner RS ,Baumbach A ,Böhm M ,Burri H ,Butler J ,Čelutkienė J ,Chioncel O ,Cleland JGF ,Coats AJS ,Crespo-Leiro MG ,Farmakis D ,Gilard M ,Heymans S ,Hoes AW ,Jaarsma T ,Jankowska EA ,Lainscak M ,Lam CSP Lyon AR ,McMurray JJV ,Mebazaa A ,Mindham R ,Muneretto C ,Piepoli MF ,Price S ,Rosano GMC ,Ruschitzka F ,Skibelund AK ,ESC Scientific Document Group .2021 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure . Eur Heart J 2021 ; 42 : 3599 – 3726 . 2. Packer M ,Butler J ,Zannad F ,Filippos G ,Ferreira JP ,Pocock SJ ,Carson P ,Anand I ,Doehner W ,Haass M ,Komajda M ,Miller A ,Pehrson S ,Teerlink JR ,Schnaidt S ,Zeller C ,Schnee JM ,Anker SD .Effect of empagliflozin on worsening heart failure events in patients with heart failure and preserved ejection fraction: EMPEROR-Preserved trial. Circulation 2021 ; 144 : 1284 – 1294 . 3. Packer M ,Zannad F ,Anker SD .Heart failure and a preserved ejection fraction: a side-by-side examination of the PARAGON-HF and EMPEROR-Preserved trials . Circulation 2021 ; 144 : 1193 – 1195 . © 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. CitationsViewsAltmetricEmail alertsCiting articles via
More from Oxford Academic Do SGLT2 inhibitors improve ejection fraction?SGLT2 inhibitors target cardiometabolic conditions through a variety of mechanisms, and have been shown to reduce the risk of cardiovascular (CV) death or worsening HF, and to improve health status in patients with HF with reduced ejection fraction (HFrEF), regardless of diabetes status10,11,12,13.
Are SGLT2 approved for HFpEF?On February 24, 2022, the U.S. Food and Drug Administration (FDA) approved the sodium-glucose cotransporter 2 (SGLT2) inhibitor empagliflozin 10 mg for the reduction of hard outcomes in adults with heart failure with preserved ejection fraction (HFpEF).
Is Empagliflozin FDA approved for heart failure with preserved ejection fraction?Empagliflozin now has FDA approval for reducing cardiovascular death or hospitalization among patients with heart failure with preserved left ventricular ejection fraction, defined as more than 40%, with or without diabetes.
What is the best treatment for HFpEF?Calcium channel blockers – In patients with HFpEF, calcium channel blockers are generally used as a third- or fourth-line therapy for hypertension. Ineffective therapies — Organic nitrates, phosphodiesterase-5 inhibitors, and digoxin are ineffective for the treatment of HFpEF.
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Sglt2 inhibitors heart failure preserved ejection fraction
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