SGLT2 inhibitors for primary and secondary prevention of cardiovascular and renal outcomes in type 2 diabetes: a systematic review and meta-analysis of cardiovascular outcome trials.

Cardiovascular Diseases / etiology Diabetes Mellitus, Type 2 / complications Diabetic Nephropathies / etiology Humans Primary Prevention / methods Secondary Prevention / methods Sodium-Glucose Transporter 2 Inhibitors / therapeutic use

Journal

Lancet (London, England)
ISSN: 1474-547X
Titre abrégé: Lancet
Pays: England
ID NLM: 2985213R

Informations de publication

Date de publication:
05 01 2019
Historique:
received: 02 10 2018
revised: 10 10 2018
accepted: 11 10 2018
pubmed: 15 11 2018
medline: 15 1 2019
entrez: 15 11 2018
Statut: ppublish

Résumé

The magnitude of effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on specific cardiovascular and renal outcomes and whether heterogeneity is based on key baseline characteristics remains undefined. We did a systematic review and meta-analysis of randomised, placebo-controlled, cardiovascular outcome trials of SGLT2i in patients with type 2 diabetes. We searched PubMed and Embase for trials published up to Sept 24, 2018. Data search and extraction were completed with a standardised data form and any discrepancies were resolved by consensus. Efficacy outcomes included major adverse cardiovascular events (myocardial infarction, stroke, or cardiovascular death), the composite of cardiovascular death or hospitalisation for heart failure, and progression of renal disease. Hazard ratios (HRs) with 95% CIs were pooled across trials, and efficacy outcomes were stratified by baseline presence of atherosclerotic cardiovascular disease, heart failure, and degree of renal function. We included data from three identified trials and 34 322 patients (60·2% with established atherosclerotic cardiovascular disease), with 3342 major adverse cardiovascular events, 2028 cardiovascular deaths or hospitalisation sfor heart failure events, and 766 renal composite outcomes. SGLT2i reduced major adverse cardiovascular events by 11% (HR 0·89 [95% CI 0·83-0·96], p=0·0014), with benefit only seen in patients with atherosclerotic cardiovascular disease (0·86 [0·80-0·93]) and not in those without (1·00 [0·87-1·16], p for interaction=0·0501). SGLT2i reduced the risk of cardiovascular death or hospitalisation for heart failure by 23% (0·77 [0·71-0·84], p<0·0001), with a similar benefit in patients with and without atherosclerotic cardiovascular disease and with and without a history of heart failure. SGLT2i reduced the risk of progression of renal disease by 45% (0·55 [0·48-0·64], p<0·0001), with a similar benefit in those with and without atherosclerotic cardiovascular disease. The magnitude of benefit of SGLT2i varied with baseline renal function, with greater reductions in hospitalisations for heart failure (p for interaction=0·0073) and lesser reductions in progression of renal disease (p for interaction=0·0258) in patients with more severe kidney disease at baseline. SGLT2i have moderate benefits on atherosclerotic major adverse cardiovascular events that seem confined to patients with established atherosclerotic cardiovascular disease. However, they have robust benefits on reducing hospitalisation for heart failure and progression of renal disease regardless of existing atherosclerotic cardiovascular disease or a history of heart failure. None.

Sections du résumé

BACKGROUND
The magnitude of effect of sodium-glucose cotransporter-2 inhibitors (SGLT2i) on specific cardiovascular and renal outcomes and whether heterogeneity is based on key baseline characteristics remains undefined.
METHODS
We did a systematic review and meta-analysis of randomised, placebo-controlled, cardiovascular outcome trials of SGLT2i in patients with type 2 diabetes. We searched PubMed and Embase for trials published up to Sept 24, 2018. Data search and extraction were completed with a standardised data form and any discrepancies were resolved by consensus. Efficacy outcomes included major adverse cardiovascular events (myocardial infarction, stroke, or cardiovascular death), the composite of cardiovascular death or hospitalisation for heart failure, and progression of renal disease. Hazard ratios (HRs) with 95% CIs were pooled across trials, and efficacy outcomes were stratified by baseline presence of atherosclerotic cardiovascular disease, heart failure, and degree of renal function.
FINDINGS
We included data from three identified trials and 34 322 patients (60·2% with established atherosclerotic cardiovascular disease), with 3342 major adverse cardiovascular events, 2028 cardiovascular deaths or hospitalisation sfor heart failure events, and 766 renal composite outcomes. SGLT2i reduced major adverse cardiovascular events by 11% (HR 0·89 [95% CI 0·83-0·96], p=0·0014), with benefit only seen in patients with atherosclerotic cardiovascular disease (0·86 [0·80-0·93]) and not in those without (1·00 [0·87-1·16], p for interaction=0·0501). SGLT2i reduced the risk of cardiovascular death or hospitalisation for heart failure by 23% (0·77 [0·71-0·84], p<0·0001), with a similar benefit in patients with and without atherosclerotic cardiovascular disease and with and without a history of heart failure. SGLT2i reduced the risk of progression of renal disease by 45% (0·55 [0·48-0·64], p<0·0001), with a similar benefit in those with and without atherosclerotic cardiovascular disease. The magnitude of benefit of SGLT2i varied with baseline renal function, with greater reductions in hospitalisations for heart failure (p for interaction=0·0073) and lesser reductions in progression of renal disease (p for interaction=0·0258) in patients with more severe kidney disease at baseline.
INTERPRETATION
SGLT2i have moderate benefits on atherosclerotic major adverse cardiovascular events that seem confined to patients with established atherosclerotic cardiovascular disease. However, they have robust benefits on reducing hospitalisation for heart failure and progression of renal disease regardless of existing atherosclerotic cardiovascular disease or a history of heart failure.
FUNDING
None.

Identifiants

DOI: 10.1016/S0140-6736(18)32590-X PMID: 30424892
pubmed: 30424892
pii: S0140-6736(18)32590-X
doi: 10.1016/S0140-6736(18)32590-X
pii:
doi:

Substances chimiques

Sodium-Glucose Transporter 2 Inhibitors 0

Types de publication

Journal Article Meta-Analysis Research Support, Non-U.S. Gov't Systematic Review

Langues

eng

Sous-ensembles de citation

IM

Pagination

31-39

Commentaires et corrections

Type : CommentIn
Type : CommentIn
Type : CommentIn
Type : CommentIn
Type : ErratumIn

Informations de copyright

Copyright © 2019 Elsevier Ltd. All rights reserved.

Auteurs

Thomas A Zelniker (TA)

TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA.

Stephen D Wiviott (SD)

TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA.

Itamar Raz (I)

The Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, Hebrew University of Jerusalem, The Faculty of Medicine, Jerusalem, Israel.

Kyungah Im (K)

TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA.

Erica L Goodrich (EL)

TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA.

Marc P Bonaca (MP)

TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA.

Ofri Mosenzon (O)

The Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, Hebrew University of Jerusalem, The Faculty of Medicine, Jerusalem, Israel.

Eri T Kato (ET)

Department of Cardiovascular Medicine, Kyoto University Graduate School of Medicine, Kyoto, Japan.

Avivit Cahn (A)

The Diabetes Unit, Department of Endocrinology and Metabolism, Hadassah Medical Center, Hebrew University of Jerusalem, The Faculty of Medicine, Jerusalem, Israel.

Remo H M Furtado (RHM)

TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA.

Deepak L Bhatt (DL)

TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA.

Lawrence A Leiter (LA)

Li Ka Shing Knowledge Institute, St Michael's Hospital, University of Toronto, Toronto, ON, Canada.

Darren K McGuire (DK)

Division of Cardiology, University of Texas Southwestern Medical Center, Dallas, TX, USA.

John P H Wilding (JPH)

Institute of Ageing and Chronic Disease, University of Liverpool, Liverpool, UK.

Marc S Sabatine (MS)

TIMI Study Group, Cardiovascular Division, Brigham and Women's Hospital, Boston, MA, USA. Electronic address: msabatine@bwh.harvard.edu.

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Classifications MeSH

questionsmedicales.fr › Maladies cardiovasculaires › SGLT2 inhibitors for primary and secondary...
questionsmedicales.fr › Maladies endocriniennes › Diabète › Diabète de type 2 › SGLT2 inhibitors for primary and secondary...
questionsmedicales.fr › Maladies endocriniennes › Diabète › Complications du diabète › Néphropathies diabétiques › SGLT2 inhibitors for primary and secondary...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › SGLT2 inhibitors for primary and secondary...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Pratiques en santé publique › Prévention primaire › SGLT2 inhibitors for primary and secondary...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Pratiques en santé publique › Prévention secondaire › SGLT2 inhibitors for primary and secondary...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Effets physiologiques des médicaments › Hypoglycémiants › Inhibiteurs du cotransporteur sodium-glucose de type 2 › SGLT2 inhibitors for primary and secondary...