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Meta-Analysis
. 2023 Mar-Apr;75(2):122-127.
doi: 10.1016/j.ihj.2023.03.003. Epub 2023 Mar 11.

SGLT2 inhibitors and cardiovascular outcomes in heart failure with mildly reduced and preserved ejection fraction: A systematic review and meta-analysis

Mainak Banerjee  1 , Rimesh Pal  2 , Kirthana Nair  2 , Satinath Mukhopadhyay  3
Affiliations
Meta-Analysis

SGLT2 inhibitors and cardiovascular outcomes in heart failure with mildly reduced and preserved ejection fraction: A systematic review and meta-analysis

Mainak Banerjee et al. Indian Heart J. 2023 Mar-Apr.

Abstract

Aim: To provide a pooled effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on cardiovascular outcomes in patients with heart failure with preserved ejection fraction (HFpEF: ≥50%) or/and mildly reduced EF (HFmrEF: 41-49%) regardless of baseline diabetes.

Methods: We systemically searched PubMed/MEDLINE, Embase, Web of Science databases and clinical trial registries using appropriate keywords till August 28, 2022, to identify randomized controlled trials (RCTs) or post-hoc analysis of RCTs, reporting cardiovascular death (CVD) and/or urgent visits/hospitalization for heart failure(HHF) in patients with HFmrEF/HFpEF receiving SGLTi vs. placebo. Hazard ratios (HR) with 95% confidence intervals (CI) for outcomes were pooled together using generic inverse variance method with fixed-effects model.

Results: We identified six RCTs, pooling data retrieved from 15,769 patients with HFmrEF/HFpEF. Pooled analysis showed that compared to placebo, SGLT2i use was significantly associated with improved CVD/HHF outcomes in HFmrEF/HFpEF (pooled HR 0.80, 95% CI: 0.74, 0.86, p < 0.001, I2 = 0%). When separately analyzed, benefits of SGLT2i remained significant across HFpEF (N = 8891, HR 0.79, 95% CI: 0.71, 0.87, p < 0.001, I2 = 0%) and HFmrEF (N = 4555, HR 0.77, 95% CI: 0.67, 0.89, p < 0.001, I2 = 40%). Consistent benefits were observed also in HFmrEF/HFpEF subgroup without baseline diabetes (N = 6507, HR 0.80, 95% CI: 0.70, 0.91, p < 0.001, I2 = 0%). Sensitivity analysis including the DELIVER and EMPEROR-Preserved trials found a trend towards significant beneficial effects on CV deaths with no heterogeneity (HR 0.90, 95% CI: 0.79, 1.02, p = 0.08, I2 = 0%).

Conclusions: This meta-analysis established the place of SGLT2i as a foundational therapy among patients with HF with preserved and mildly reduced EF regardless of diabetes.

Keywords: Dapagliflozin; Empagliflozin; Heart failure; SGLT2 inhibitors; Sotagliflozin; T2DM.

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Conflict of interest statement

None to declare.

Figures

Fig. 1
Fig. 1
Risk of composite cardiovascular outcomes of CVD/HHF in patients with HFpEF and/or HFmrEF receiving SGLT2 inhibitors versus placebo Abbreviations: CVD, cardiovascular death; HHF, hospitalization for heart failure; HFpEF, Heart failure with preserved ejection fraction; HFmrEF, Heart failure with mildly reduced ejection fraction.
Fig. 2
Fig. 2
Subgroup analysis showing impact of baseline diabetes on risk of composite cardiovascular outcomes of CVD/HHF in patients with HFpEF and/or HFmrEF receiving SGLT2 inhibitors versus placebo Abbreviations: CVD, cardiovascular death; HHF, hospitalization for heart failure; HFpEF, Heart failure with preserved ejection fraction; HFmrEF, Heart failure with mildly reduced ejection fraction.
See this image and copyright information in PMC

References

    1. Borlaug B.A. Evaluation and management of heart failure with preserved ejection fraction. Nat Rev Cardiol. 2020;17:559–573. doi: 10.1038/s41569-020-0363-2. - DOI - PubMed
    1. McDonagh T.A., Metra M., Adamo M., et al. ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure. Eur Heart J. 2021;2021(42):3599–3726. doi: 10.1093/eurheartj/ehab368. - DOI - PubMed
    1. Heidenreich P.A., Bozkurt B., Aguilar D., et al. AHA/ACC/HFSA guideline for the management of heart failure: a report of the American College of cardiology/American heart association joint committee on clinical practice guidelines. Circulation. 2022;145 doi: 10.1161/CIR.0000000000001063. 2022. - DOI - PubMed
    1. Savarese G., Stolfo D., Sinagra G., Lund L.H. Heart failure with mid-range or mildly reduced ejection fraction. Nat Rev Cardiol. 2022;19:100–116. doi: 10.1038/s41569-021-00605-5. - DOI - PMC - PubMed
    1. Zelniker T.A., Braunwald E. Mechanisms of cardiorenal effects of sodium-glucose cotransporter 2 inhibitors. J Am Coll Cardiol. 2020;75:422–434. doi: 10.1016/j.jacc.2019.11.031. - DOI - PubMed

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