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Meta-Analysis
. 2022 Feb 5;21(1):20.
doi: 10.1186/s12933-022-01455-2.

Efficacy and safety of sodium-glucose cotransporter 2 inhibitors initiation in patients with acute heart failure, with and without type 2 diabetes: a systematic review and meta-analysis

Husam M Salah  1 , Subhi J Al'Aref  1 , Muhammad Shahzeb Khan  2 , Malek Al-Hawwas  1 , Srikanth Vallurupalli  1 , Jawahar L Mehta  1 , J Paul Mounsey  1 , Stephen J Greene  2   3 , Darren K McGuire  4 , Renato D Lopes  2   3 , Marat Fudim  5   6
Affiliations
Meta-Analysis

Efficacy and safety of sodium-glucose cotransporter 2 inhibitors initiation in patients with acute heart failure, with and without type 2 diabetes: a systematic review and meta-analysis

Husam M Salah et al. Cardiovasc Diabetol. .

Abstract

Background: There is uncertainty and limited data regarding initiation of sodium-glucose cotransporter 2 (SGLT2) inhibitors among patients hospitalized with acute heart failure (AHF). This systematic review and meta-analysis aim to establish the efficacy and safety of SGLT2 inhibitors initiated in patients hospitalized for AHF.

Methods: PubMed/Medline, Embase, and Cochrane library were searched using the following terms: ("sglt2" and "acute heart failure") and ("sglt2" and "worsening heart failure") from inception till November 15th, 2021 for randomized controlled trials (RCTs) comparing the efficacy and safety of initiating an SGLT2 inhibitor compared with placebo in patients with AHF. Major cardiovascular and diabetes scientific meetings in 2021 were also searched for relevant studies. Prespecified efficacy outcomes were all-cause mortality, rehospitalization for heart failure, and improvement in Kansas City Cardiomyopathy Questionnaire (KCCQ) scale score. Prespecified safety outcomes were acute kidney injury (AKI), hypotension, and hypoglycemia. Random effects odds ratio (OR) and mean difference with 95% confidence intervals (CIs) were calculated.

Results: Three RCTs with a total of 1831 patients were included. Initiation of SGLT2 inhibitors in patients with AHF reduced the risk of rehospitalization for heart failure (OR 0.52; 95% CI [0.42, 0.65]) and improved Kansas City Cardiomyopathy Questionnaire scores (mean difference 4.12; 95% CI [0.1.89, 6.53]). There was no statistically significant effect for initiation of SGLT2 inhibitors in patients with AHF on all-cause mortality (OR 0.70; 95% CI [0.46, 1.08]). Initiation of SGLT2 inhibitors in patients with AHF did not increase the acute kidney injury (OR 0.76; 95% CI [0.50, 1.16]), hypotension (OR 1.17; 95% CI [0.80, 1.71]), or hypoglycemia (OR 1.51; 95% CI [0.86, 2.65]).

Conclusion: Initiation of SGLT2 inhibitors in patients hospitalized for AHF during hospitalization or early post-discharge (within 3 days) reduces the risk of rehospitalization for heart failure and improves patient-reported outcomes with no excess risk of adverse effects.

Keywords: Acute; Heart failure; Initiation; Meta-analysis; Outcomes; Sodium-glucose cotransporter 2 inhibitors; Systematic review.

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Conflict of interest statement

Al’Aref: Supported by NIH 2R01 HL127661-05, receives royalty fees from Elsevier. Mehta has previously served as consultant to Bayer, Boehringer Ingelheim, AstraZeneca, MedImmmune and Pfizer; and received grant support from Bayer, Boehringer Ingelheim and AstraZeneca. Current grant support from Department of Veterans Affairs, Veterans Health Administration, Office of Research and Development, Biomedical Laboratory Research and Development (Washington, DC, USA) (Grant No. BX-000282–05). Greene: has received research support from Amgen, AstraZeneca, Bristol Myers Squibb, Cytokinetics, Merck, Novartis, Pfizer, and Sanofi; serves on advisory boards for Amgen, AstraZeneca, Bristol Myers Squibb, Cytokinetics, and Sanofi; and serves as a consultant for Amgen, Bayer, Merck, and Vifor. McGuire: has received personal fees for trial leadership and/or consultancy from Boehringer Ingelheim, Janssen Research and Development LLC, Sanofi US, Merck Sharp and Dohme Corp., Eli Lilly USA, Novo Nordisk, GlaxoSmithKline, AstraZeneca, Lexicon Pharmaceuticals, Eisai, Pfizer, Metavant, Applied Therapeutics, Afimmune and Esperion. Lopes: research grants and personal fees from Bristol-Myers Squibb and Pfizer, personal fees from Boehringer Ingelheim and Bayer AG and grants from Amgen Inc, GlaxoSmithKline, Medtronic PLC, and Sanofi Aventis outside the submitted work. Fudim: Supported by the Mario Family Award, Translating Duke Health Award; Duke Medicine Chair’s Award, consulting fees from AstraZeneca, AxonTherapies, CVRx, Daxor, Edwards LifeSciences, Galvani, NXT Biomedical and Respicardia. All other authors report no relevant disclosures.

Figures

Fig. 1
Fig. 1
Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flow diagram for the included studies
Fig. 2
Fig. 2
Risk of bias assessment using the Risk of Bias 2.0 tool. As the EMPUSLE trial results are not published yet, its risk of bias assessment was done based on its published design and the publicly available American Heart Association 2021 presentation
Fig. 3
Fig. 3
Forest plots examining the efficacy endpoints of sodium-glucose cotransporter 2 inhibitors initiation in patients with acute heart failure. Events in the analyses represent total number of events rather than time-to-event endpoint data. SGLT2: sodium-glucose cotransporter 2; HF: heart failure; KCCQ: Kansas City Cardiomyopathy Questionnaire; M–H: Mantel–Haenszel; CI: confidence interval
Fig. 4
Fig. 4
Forest plots examining the safety endpoints of sodium-glucose cotransporter 2 inhibitors initiation in patients with acute heart failure. Events in the analyses represent total number of events rather than time-to-event endpoint data. SGLT2: sodium-glucose cotransporter 2; HF: heart failure; AKI: acute kidney injury; M–H: Mantel–Haenszel; CI: confidence interval
Fig. 5
Fig. 5
Results of sensitivity analyses excluding the results of the unpublished EMPUSLE trial
See this image and copyright information in PMC

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