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Efficacy and safety of sodium-glucose cotransporter-2 inhibitors in heart failure with mildly reduced or preserved ejection fraction: an overview of 36 systematic reviews

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Abstract

The recently published randomized trials (RCTs) evaluating the effect of Sodium-glucose cotransporter-2 inhibitors (SGLT2i) in heart failure with mildly reduced (HFmrEF) or preserved ejection fraction (HFpEF) led researchers to perform a plethora of systematic reviews (SRs), often providing contradictory conclusions. This overview of reviews was aimed at summarizing the evidence of these SRs, quantifying the overlap, re-analyzing the evidence in case new studies that were identified, and mapping knowledge gaps. Literature search was conducted through Medline, Scopus, and Cochrane until March 22, 2023. Overall, 36 SRs synthesizing results from 18 RCTs were identified. A substantial overlap was identified among the SRs synthesizing large heart failure or cardiovascular outcome trials (CVOTs). Regarding the composite outcome of cardiovascular (CV) mortality or hospitalization for heart failure (HHF), all authors reported a significant favorable effect. A beneficial effect was also noted for CV and all-cause mortality, albeit not significant. Our meta-analysis demonstrated a significant improvement in health-related quality-of-life (HRQoL) as assessed by the Kansas City Cardiomyopathy Questionnaire Overall Summary Score (KCCQ-OSS, MD = 1.97, p < 0.001), Total Symptom Score (KCCQ-TSS, MD = 2.29, p < 0.001), Clinical Summary Score (KCCQ-CSS, MD = 1.59, p < 0.001), and the 6-min walking distance (MD = 10.78 m, p = 0.032). Regarding safety, SGLT2i were associated with a significantly lower risk of serious adverse events compared to placebo (RR = 0.94, p = 0.002). The use of SGLT2i in HFpEF is both efficient and safe. Further research is required to clarify the impact of SGTL2i on different subphenotypes of HFpEF and the cardiorespiratory capacity of these patients.

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Data availability

All data extracted and analyzed in this study can be accessed here (https://osf.io/p6a9w/).

Abbreviations

CV:

Cardiovascular

HHF:

Hospitalization for heart failure

HFmrEF:

Heart failure with mildly reduced ejection fraction

HFpEF:

Heart failure with preserved ejection fraction

SGLT2i:

Sodium-glucose cotransporter-2 inhibitors

KCCQ-TSS:

Kansas City Cardiomyopathy Questionnaire Total Symptom Score

KCCQ-CSS:

Clinical Summary Score

KCCQ-OSS:

Overall Summary Score

KCCQ-PL:

Physical Limitation

6MWD:

6-Minute walk distance

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Authors and Affiliations

  1. Second Cardiology Department, Medical School, Hippokration General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece

    Paschalis Karakasis, Panagiotis Stachteas, Dimitrios Patoulias & Nikolaos Fragakis

  2. Department of Hygiene, Social-Preventive Medicine & Medical Statistics, Medical School, Aristotle University of Thessaloniki, University Campus, 54124, Thessaloniki, Greece

    Paschalis Karakasis, Konstantinos Pamporis & Konstantinos I. Bougioukas

  3. Second Department of Internal Medicine, European Interbalkan Medical Center, 57001, Thessaloniki, Greece

    Dimitrios Patoulias

  4. Outpatient Department of Cardiometabolic Medicine, Second Department of Cardiology, General Hospital Hippokration, Aristotle University of Thessaloniki, 54642, Thessaloniki, Greece

    Dimitrios Patoulias

Authors
  1. Paschalis Karakasis
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  2. Konstantinos Pamporis
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  3. Panagiotis Stachteas
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  4. Dimitrios Patoulias
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  5. Konstantinos I. Bougioukas
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  6. Nikolaos Fragakis
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Contributions

Paschalis Karakasis: conceptualization, methodology, investigation, formal analysis, data curation, visualization, project administration, writing original draft, writing, review, and editing. Konstantinos Pamporis: methodology, writing original draft, writing, review, and editing. Panagiotis Stachteas: writing original draft, writing, review, and editing. Dimitrios Patoulias: writing original draft, writing, review, and editing. Konstantinos I. Bougioukas: methodology, writing original draft, writing, review, and editing. Nikolaos Fragakis: conceptualization, methodology, validation, writing, review, editing, and supervision.

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Correspondence to Paschalis Karakasis.

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The authors declare no competing interests.

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The study protocol was prospectively registered in OSF (https://osf.io/p6a9w/).

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Karakasis, P., Pamporis, K., Stachteas, P. et al. Efficacy and safety of sodium-glucose cotransporter-2 inhibitors in heart failure with mildly reduced or preserved ejection fraction: an overview of 36 systematic reviews. Heart Fail Rev 28, 1033–1051 (2023). https://doi.org/10.1007/s10741-023-10324-3

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