Sindone, A., Atherton, J., Deed, G., Molloy-Bland, M., Cohen, N., and Rasalam, R. (2021) Systematic review of the effects of sodium-glucose cotransporter 2 inhibitors on hospitalisation for heart failure and cardiac structure or function, and exploratory assessment of potential mechanisms. Heart, Lung and Circulation, 30 (Supplement 3). 101. S136-S137.

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Abstract

Aims: To systematically review randomised controlled trials assessing effects of sodium-glucose cotransporter 2 inhibitors (SGLT2is) on hospitalisation for heart failure (HHF) and cardiac structure/function and explore 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% versus 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 improve- ments versus 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 versus 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 sug- gests 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: SGLT2is 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:	71283
Item Type:	Article (Abstract)
ISSN:	1444-2892
Keywords:	sodium glucose cotransport inhibitor; heart failure; type 2 diabetes
Additional Information:	CSANZ 2021: 69th Annual Scientific Meeting of the Cardiac Society of Australia and New Zealand, 5-8 Ausgust 2022, Adelaide,SA, Australia
Date Deposited:	18 Jan 2022 21:25
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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