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Shamliyan et al. Vessel Plus 2020;4:35 Vessel Plus
DOI: 10.20517/2574-1209.2020.34

Systematic Review Open Access

Insufficient evidence regarding benefits from
sodium-glucose cotransporter-2 inhibitors in heart

failure with preserved ejection fraction

Tatyana A. Shamliyan , Anna A. Avanesova , Wilbert S. Aronow 3
1
2
1 Carvell Health Services, Inc, Cheltenham, PA 19012, USA.
2 North-Caucasus Federal University, Stavropol 355000, Russian Federation.
3 Departments of Cardiology and Medicine, Westchester Medical Center and New York Medical College, Valhalla, NY 10595,
USA.
Correspondence to: Dr. Tatyana A. Shamliyan, Carvell Health Services, Inc, Cheltenham, PA 19012, USA.
E-mail: shaml005@umn.edu
How to cite this article: Shamliyan TA, Avanesova AA, Aronow WS. Insufficient evidence regarding benefits from sodium-
glucose cotransporter-2 inhibitors in heart failure with preserved ejection fraction. Vessel Plus 2020;4:35.
http://dx.doi.org/10.20517/2574-1209.2020.34

Received: 27 Jul 2020 First Decision: 19 Oct 2020 Revised: 22 Oct 2020 Accepted: 28 Oct 2020 Published: 18 Nov 2020
Received: First Decision: Revised: Accepted: Published: x Academic Editor: Ryuuichi Morishita Copy Editor: Cai-Hong Wang Production Editor: Jing Yu

Science Editor: Copy Editor: Production Editor: Jing Yu
Abstract
Aim: Sodium-glucose cotransporter-2 (SGLT2)-inhibitors improve survival in adults with reduced ejection fraction.
Clinical outcomes in adults with heart failure (HF) with preserved ejection fraction (HFpEF) have not been
systematically reviewed.

Methods: We conducted a systematic rapid literature review and appraised the quality of evidence using the
Grading of Recommendations Assessment, Development and Evaluation methodology.

Results: We identified post-hoc subgroup analyses of four randomized controlled clinical trials (RCTs) and
unpublished results from 2 RCTs. In 2 RCTs vs. placebo, Canagliflozin reduced the risk of fatal or hospitalized HF in
adults with HF and documented or assumed left ventricular ejection fraction (LVEF) ≥ 50% (hazard rate ratio, HR
= 0.71, 95%CI: 0.52-0.97) but had no effect in a subpopulation with documented LVEF ≥ 50% (HR = 0.83, 95%CI:
0.55-1.25). Dapagliflozin or ertugliflozin did not improve all-cause or cardiovascular death or hospitalization for HF
in adults with HF and LVEF > 45% in two pivotal RCTs vs. placebo. Empagliflozin did not improve exercise ability,
patient-reported outcomes or congestion, diuretic use and all-cause healthcare resource utilization in unpublished
RCT vs. placebo. Various definitions of HFpEF, post-hoc interaction analyses suggesting outcome improvement

© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0
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sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
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and indicate if changes were made.

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