Sodium-glucose cotransporter 2 inhibitor effects on heart failure hospitalization and cardiac function: systematic review

Rasalam, Roy, Atherton, John J., Deed, Gary, Molloy-Bland, Michael, Cohen, Neale, and Sindone, Andrew (2021) Sodium-glucose cotransporter 2 inhibitor effects on heart failure hospitalization and cardiac function: systematic review. ESC Heart Failure, 8 (5). pp. 4093-4118.

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Abstract

Aims: To systematically review randomized controlled trials assessing effects of sodium–glucose cotransporter 2 inhibitors (SGLT2is) on hospitalization for heart failure (HHF) and cardiac structure/function and explore randomized controlled trial (RCT)-derived evidence for SGLT2i efficacy mechanisms in heart failure (HF).

Methods and results: Systematic searches of Medline and Embase were performed. In seven trials [3730–17 160 patients; low risk of bias (RoB)], SGLT2is significantly reduced the relative risk of HHF by 27–39% vs. placebo, including in two studies in patients with HF with reduced ejection fraction with or without type-2 diabetes mellitus (T2DM). Improvements in conventional cardiovascular risk factors, including glycaemic levels, cannot account for these effects. Five trials (56–105 patients; low RoB) assessed the effects of 6–12 months of SGLT2i treatment on left ventricular structure/function; four reported significant improvements vs. placebo, and one did not. Five trials (low RoB) assessed SGLT2i treatment effects on serum N-terminal pro B-type natriuretic peptide levels; significant reductions vs. placebo were reported after 8–12 months (two studies; 3730–4744 patients) but not ≤12 weeks (three studies; 80–263 patients). Limited available RCT-derived evidence suggests various possible cardioprotective SGLT2i mechanisms, including improved haemodynamics (natriuresis and reduced interstitial fluid without blood volume contraction/neurohormonal activation) and vascular function, enhanced erythropoiesis, reduced tissue sodium and epicardial fat/inflammation, decreased sympathetic tone, and beneficial changes in cellular energetics.

Conclusions: Sodium–glucose cotransporter 2 inhibitors reduce HHF regardless of T2DM status, and reversal of adverse left ventricular remodelling likely contributes to this efficacy. Hypothesis-driven mechanistic trials remain sparse, although numerous trials are planned or ongoing.

Item ID: 69212
Item Type: Article (Research - C1)
ISSN: 2055-5822
Keywords: systematic review; randomised controlled trials; sodium-glucose cotransporter 2 inhibitors; heart failure
Copyright Information: © 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology. This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes
Date Deposited: 30 Aug 2021 21:49
FoR Codes: 32 BIOMEDICAL AND CLINICAL SCIENCES > 3202 Clinical sciences > 320208 Endocrinology @ 40%
32 BIOMEDICAL AND CLINICAL SCIENCES > 3201 Cardiovascular medicine and haematology > 320101 Cardiology (incl. cardiovascular diseases) @ 60%
SEO Codes: 20 HEALTH > 2001 Clinical health > 200102 Efficacy of medications @ 60%
20 HEALTH > 2001 Clinical health > 200105 Treatment of human diseases and conditions @ 40%
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