Sodium Glucose Co-transporter 2 Inhibitors and Major Adverse Cardiovascular Outcomes: A SMART-C Collaborative Meta-Analysis - Université de Lorraine
Journal Articles Circulation Year : 2024

Sodium Glucose Co-transporter 2 Inhibitors and Major Adverse Cardiovascular Outcomes: A SMART-C Collaborative Meta-Analysis

1 Brigham and Women's Hospital [Boston]
2 HMS - Harvard Medical School [Boston]
3 UNSW - University of New South Wales [Sydney]
4 GIGH - The George Institute for Global Health [Sydney]
5 RNSH - Royal North Shore Hospital
6 Charité - UniversitätsMedizin = Berlin University Medicine
7 Berlin Institute of Health Center for Regenerative Therapies (BCRT)
8 DZHK - German Center for Cardiovascular Research
9 MSSM - Icahn School of Medicine at Mount Sinai [New York]
10 BSWRI - Baylor Scott & White Research Institute
11 UMMC - University of Mississippi Medical Center
12 TGHRI - Toronto General Hospital Research Institute [Canada]
13 Nuffield Department of Population Health [Oxford]
14 University of Oxford
15 YSM - Yale School of Medicine [New Haven, Connecticut]
16 Stanford School of Medicine [Stanford]
17 University of Texas Southwestern Medical Center [Dallas]
18 BHF GCRC - British Heart Foundation Glasgow Cardiovascular Research Centre
19 University of New South Wales [Kensington]
20 Imperial College London
21 BCM - Baylor College of Medicine
22 BWH - Brigham & Women’s Hospital [Boston]
23 University Hospital Wuerzburg / Universitäts­klinikum Würzburg
24 UCL - University College of London [London]
25 DCAC - Défaillance Cardiovasculaire Aiguë et Chronique
26 CIC-P - Centre d'investigation clinique plurithématique Pierre Drouin [Nancy]
27 INI-CRCT - Cardiovascular and Renal Clinical Trialists [Vandoeuvre-les-Nancy]
28 Cardiovascular & Renal Clinical Trialists - CRCT - French-Clinical Research Infrastructure Network - F-CRIN [Paris]
29 Merck & Co. Inc - Merck Sharp and Dohme
30 UMCG - University Medical Center Groningen [Groningen]
Meg J Jardine
Bruce Neal
Vlado Perkovic
David C Wheeler
Yujie Zhao
Marc S Sabatine
Stephen D Wiviott

Abstract

Background: Sodium glucose co-transporter 2 inhibitors (SGLT2i) consistently improve heart failure and kidney-related outcomes; however, effects on major adverse cardiovascular events (MACE) across different patient populations are less clear. Methods: This was a collaborative trial-level meta-analysis from the SGLT2i meta-analysis cardio-renal trialists consortium, which includes all phase 3, placebo-controlled, outcomes trials of SGLT2i across three patient populations (diabetes at high risk for atherosclerotic cardiovascular disease [ASCVD], heart failure [HF], or chronic kidney disease [CKD]). The outcomes of interest were MACE (composite of CV death, myocardial infarction [MI], or stroke), individual components of MACE (inclusive of fatal and non-fatal events), all-cause mortality, and death subtypes. Effect estimates for SGLT2i vs. placebo were meta-analyzed across trials and examined across key subgroups (established ASCVD, prior MI, diabetes, prior HF, albuminuria, CKD stages and risk groups). Results: A total of 78,607 patients across 11 trials were included: 42,568 (54.2%), 20,725 (26.4%), and 15,314 (19.5%) were included from trials of patients with diabetes at high risk for ASCVD, HF, or CKD, respectively. SGLT2i reduced the rate of MACE by 9% (HR 0.91 [95% CI 0.87-0.96], p<0.0001) with a consistent effect across all three patient populations ( I 2 =0%) and across all key subgroups. This effect was primarily driven by a reduction in CV death (HR 0.86 [0.81-0.92], p<0.0001), with no significant effect for MI in the overall population (HR 0.95 [0.87-1.04], p=0.29), and no effect on stroke (HR 0.99 [0.91-1.07], p=0.77). The benefit for CV death was driven primarily by reductions in HF death and sudden cardiac death (HR 0.68 [0.46-1.02] and HR 0.86 [0.78-0.95], respectively) and was generally consistent across subgroups, with the possible exception of being more apparent in those with albuminuria (P int =0.02). Conclusions: SGLT2i reduce the risk of MACE across a broad range of patients irrespective of ASCVD, diabetes, kidney function or other major clinical characteristics at baseline. This effect is driven primarily by a reduction of CV death, particularly HF and sudden cardiac death, without a significant effect on MI in the overall population, and no effect on stroke. These data may help inform selection for SGLT2i therapies across the spectrum of cardiovascular-kidney-metabolic disease.
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hal-04540925 , version 1 (10-04-2024)

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Siddharth M Patel, Yu Mi Kang, Kyungah Im, Brendon L Neuen, Stefan D Anker, et al.. Sodium Glucose Co-transporter 2 Inhibitors and Major Adverse Cardiovascular Outcomes: A SMART-C Collaborative Meta-Analysis. Circulation, 2024, ⟨10.1161/CIRCULATIONAHA.124.069568⟩. ⟨hal-04540925⟩
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