Impact of SGLT2 inhibition on markers of reverse cardiac remodelling in heart failure: Systematic review and meta‐analysis

Abstract Introduction Several landmark randomized‐controlled trials (RCTs) have demonstrated the efficacy of sodium‐glucose co‐transport 2 (SGLT2) inhibitors in reducing all‐cause mortality, cardiovascular (CV) mortality and heart failure (HF) hospitalizations. Much interest surrounds their mechanis...

Full description

Saved in:
Bibliographic Details
Main Authors: Patrick Savage, Chris Watson, Jaimie Coburn, Brian Cox, Michael Shahmohammadi, David Grieve, Lana Dixon
Format: Article
Language:English
Published: Wiley 2024-12-01
Series:ESC Heart Failure
Subjects:
Online Access:https://doi.org/10.1002/ehf2.14993
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1846128408533139456
author Patrick Savage
Chris Watson
Jaimie Coburn
Brian Cox
Michael Shahmohammadi
David Grieve
Lana Dixon
author_facet Patrick Savage
Chris Watson
Jaimie Coburn
Brian Cox
Michael Shahmohammadi
David Grieve
Lana Dixon
author_sort Patrick Savage
collection DOAJ
description Abstract Introduction Several landmark randomized‐controlled trials (RCTs) have demonstrated the efficacy of sodium‐glucose co‐transport 2 (SGLT2) inhibitors in reducing all‐cause mortality, cardiovascular (CV) mortality and heart failure (HF) hospitalizations. Much interest surrounds their mechanism of action and whether they have direct effects on reverse cardiac remodelling. Therefore, we conducted a meta‐analysis of placebo controlled RCTs evaluating the impact of SGLT2 inhibition on imaging derived markers of reverse cardiac remodelling in patients with HF. Methods We performed a systematic review and meta‐analysis in accordance with the Preferred Reporting Items for Systematic Review and Meta‐Analysis (PRISMA) Statement and Cochrane Collaboration. Data interrogation of each major database including PubMed, EMBASE, MEDLINE and Cochrane Library was performed. RCTs evaluating HF patients >18 years comparing SGLT2 inhibitor versus placebo‐control were included. Outcome measures included left ventricular end‐diastolic volume and volume index (LVEDV/LVEDVi), left ventricular end‐systolic volume and volume index (LVSDV/LVSDVi), left ventricular ejection fraction (LVEF), left ventricular mass index (LVMi), left atrial volume index (LAVi) and left ventricular global longitudinal strain (LV GLS). Studies with an HF with preserved ejection fraction population were excluded from analysis of parameters, which would be significantly affected by baseline LVEF, such as volumes and LVEF. The mean difference and standard error were extracted from each study and a random effects model used pool the mean difference and standard error across studies. A pre‐specified sub‐group analysis was performed to stratify results according to imaging modality used (cardiac magnetic resonance imaging and echocardiography). This study is registered on PROSPERO: CRD42023482722. Results Seven randomized, placebo‐controlled trials in patients with HF comprising a total population of 657 patients were included. Overall LVEF of included studies ranged from 29 ± 8.0% to 55.5 ± 4.2%. In studies included in analysis of HFrEF parameters, baseline LVEF ranged from 29 ± 8% to 45.5 ± 12%. Pooled data demonstrated SGLT2 inhibition, compared with placebo control, resulted in significant improvements in mean difference of LVEDV [−11.62 ml (95% confidence interval, CI −17.90 to −5.25; z = 3.67, P = 0.0004)], LVEDVi [−6.08 ml (95% CI −9.96 to −2.20; z = 3.07; P = 0.002)], LVESV [−12.47 ml (95% CI −19.12 to −5.82; z = 3.68; P = 0.0002)], LVESVi [−6.02 ml (95% CI −10.34 to −1.70; z = 2.73; P = 0.006)], LVM [−9.77 g (95% CI −17.65 to −1.89; z = 2.43; P = 0.02)], LVMi (−3.52 g [95% CI −7.04 to 0.01; z = 1.96; P = 0.05)] and LVEF [+2.54 mL (95% CI 1.10 to 3.98; z = 3.62; P = 0.0005)]. No significant difference in GLS (n = 327) [+0.42% (95%CI −0.19 to 1.02; P = 0.18)] or LAVi [−3.25 ml (95% CI −8.20 to 1.69; z = 1.29; P = 0.20)] was noted. Conclusion This meta‐analysis provides additional data and insight into the effects of SGLT2 inhibition on reverse cardiac remodelling in patients with HF. Compared with placebo control, we found that treatment with a SGLT2 inhibitor produced significant improvements in several markers of reverse cardiac remodelling.
format Article
id doaj-art-8cf3af7a010a49f2a765dca43d54c2ef
institution Kabale University
issn 2055-5822
language English
publishDate 2024-12-01
publisher Wiley
record_format Article
series ESC Heart Failure
spelling doaj-art-8cf3af7a010a49f2a765dca43d54c2ef2024-12-11T01:56:59ZengWileyESC Heart Failure2055-58222024-12-011163636364810.1002/ehf2.14993Impact of SGLT2 inhibition on markers of reverse cardiac remodelling in heart failure: Systematic review and meta‐analysisPatrick Savage0Chris Watson1Jaimie Coburn2Brian Cox3Michael Shahmohammadi4David Grieve5Lana Dixon6Wellcome‐Wolfson Institute for Experimental Medicine Queen's University Belfast Belfast UKWellcome‐Wolfson Institute for Experimental Medicine Queen's University Belfast Belfast UKRoyal Victoria Hospital Belfast UKRoyal Victoria Hospital Belfast UKRoyal Victoria Hospital Belfast UKWellcome‐Wolfson Institute for Experimental Medicine Queen's University Belfast Belfast UKWellcome‐Wolfson Institute for Experimental Medicine Queen's University Belfast Belfast UKAbstract Introduction Several landmark randomized‐controlled trials (RCTs) have demonstrated the efficacy of sodium‐glucose co‐transport 2 (SGLT2) inhibitors in reducing all‐cause mortality, cardiovascular (CV) mortality and heart failure (HF) hospitalizations. Much interest surrounds their mechanism of action and whether they have direct effects on reverse cardiac remodelling. Therefore, we conducted a meta‐analysis of placebo controlled RCTs evaluating the impact of SGLT2 inhibition on imaging derived markers of reverse cardiac remodelling in patients with HF. Methods We performed a systematic review and meta‐analysis in accordance with the Preferred Reporting Items for Systematic Review and Meta‐Analysis (PRISMA) Statement and Cochrane Collaboration. Data interrogation of each major database including PubMed, EMBASE, MEDLINE and Cochrane Library was performed. RCTs evaluating HF patients >18 years comparing SGLT2 inhibitor versus placebo‐control were included. Outcome measures included left ventricular end‐diastolic volume and volume index (LVEDV/LVEDVi), left ventricular end‐systolic volume and volume index (LVSDV/LVSDVi), left ventricular ejection fraction (LVEF), left ventricular mass index (LVMi), left atrial volume index (LAVi) and left ventricular global longitudinal strain (LV GLS). Studies with an HF with preserved ejection fraction population were excluded from analysis of parameters, which would be significantly affected by baseline LVEF, such as volumes and LVEF. The mean difference and standard error were extracted from each study and a random effects model used pool the mean difference and standard error across studies. A pre‐specified sub‐group analysis was performed to stratify results according to imaging modality used (cardiac magnetic resonance imaging and echocardiography). This study is registered on PROSPERO: CRD42023482722. Results Seven randomized, placebo‐controlled trials in patients with HF comprising a total population of 657 patients were included. Overall LVEF of included studies ranged from 29 ± 8.0% to 55.5 ± 4.2%. In studies included in analysis of HFrEF parameters, baseline LVEF ranged from 29 ± 8% to 45.5 ± 12%. Pooled data demonstrated SGLT2 inhibition, compared with placebo control, resulted in significant improvements in mean difference of LVEDV [−11.62 ml (95% confidence interval, CI −17.90 to −5.25; z = 3.67, P = 0.0004)], LVEDVi [−6.08 ml (95% CI −9.96 to −2.20; z = 3.07; P = 0.002)], LVESV [−12.47 ml (95% CI −19.12 to −5.82; z = 3.68; P = 0.0002)], LVESVi [−6.02 ml (95% CI −10.34 to −1.70; z = 2.73; P = 0.006)], LVM [−9.77 g (95% CI −17.65 to −1.89; z = 2.43; P = 0.02)], LVMi (−3.52 g [95% CI −7.04 to 0.01; z = 1.96; P = 0.05)] and LVEF [+2.54 mL (95% CI 1.10 to 3.98; z = 3.62; P = 0.0005)]. No significant difference in GLS (n = 327) [+0.42% (95%CI −0.19 to 1.02; P = 0.18)] or LAVi [−3.25 ml (95% CI −8.20 to 1.69; z = 1.29; P = 0.20)] was noted. Conclusion This meta‐analysis provides additional data and insight into the effects of SGLT2 inhibition on reverse cardiac remodelling in patients with HF. Compared with placebo control, we found that treatment with a SGLT2 inhibitor produced significant improvements in several markers of reverse cardiac remodelling.https://doi.org/10.1002/ehf2.14993heart failureSGLT2 inhibitorscardiac imagingremodellingbiomarkers
spellingShingle Patrick Savage
Chris Watson
Jaimie Coburn
Brian Cox
Michael Shahmohammadi
David Grieve
Lana Dixon
Impact of SGLT2 inhibition on markers of reverse cardiac remodelling in heart failure: Systematic review and meta‐analysis
ESC Heart Failure
heart failure
SGLT2 inhibitors
cardiac imaging
remodelling
biomarkers
title Impact of SGLT2 inhibition on markers of reverse cardiac remodelling in heart failure: Systematic review and meta‐analysis
title_full Impact of SGLT2 inhibition on markers of reverse cardiac remodelling in heart failure: Systematic review and meta‐analysis
title_fullStr Impact of SGLT2 inhibition on markers of reverse cardiac remodelling in heart failure: Systematic review and meta‐analysis
title_full_unstemmed Impact of SGLT2 inhibition on markers of reverse cardiac remodelling in heart failure: Systematic review and meta‐analysis
title_short Impact of SGLT2 inhibition on markers of reverse cardiac remodelling in heart failure: Systematic review and meta‐analysis
title_sort impact of sglt2 inhibition on markers of reverse cardiac remodelling in heart failure systematic review and meta analysis
topic heart failure
SGLT2 inhibitors
cardiac imaging
remodelling
biomarkers
url https://doi.org/10.1002/ehf2.14993
work_keys_str_mv AT patricksavage impactofsglt2inhibitiononmarkersofreversecardiacremodellinginheartfailuresystematicreviewandmetaanalysis
AT chriswatson impactofsglt2inhibitiononmarkersofreversecardiacremodellinginheartfailuresystematicreviewandmetaanalysis
AT jaimiecoburn impactofsglt2inhibitiononmarkersofreversecardiacremodellinginheartfailuresystematicreviewandmetaanalysis
AT briancox impactofsglt2inhibitiononmarkersofreversecardiacremodellinginheartfailuresystematicreviewandmetaanalysis
AT michaelshahmohammadi impactofsglt2inhibitiononmarkersofreversecardiacremodellinginheartfailuresystematicreviewandmetaanalysis
AT davidgrieve impactofsglt2inhibitiononmarkersofreversecardiacremodellinginheartfailuresystematicreviewandmetaanalysis
AT lanadixon impactofsglt2inhibitiononmarkersofreversecardiacremodellinginheartfailuresystematicreviewandmetaanalysis