Exploring the heterogeneity of the effects of SGLT-2 inhibitors in cardiovascular outcome trials.
Aged
Cardiovascular Diseases
/ diagnosis
Evidence-Based Medicine
Female
Humans
Incidence
Male
Middle Aged
Primary Prevention
Protective Factors
Randomized Controlled Trials as Topic
Research Design
Risk Assessment
Risk Factors
Secondary Prevention
Sodium-Glucose Transporter 2 Inhibitors
/ adverse effects
Treatment Outcome
Major cardiovascular events
Mortality
SGLT-2 inhibitors
Journal
Nutrition, metabolism, and cardiovascular diseases : NMCD
ISSN: 1590-3729
Titre abrégé: Nutr Metab Cardiovasc Dis
Pays: Netherlands
ID NLM: 9111474
Informations de publication
Date de publication:
03 01 2020
03 01 2020
Historique:
received:
23
01
2019
revised:
16
07
2019
accepted:
22
07
2019
pubmed:
24
11
2019
medline:
1
7
2020
entrez:
24
11
2019
Statut:
ppublish
Résumé
The interpretation of discrepancies across cardiovascular safety trials (CVOT) with SGLT-2 inhibitors in the incidence of major cardiovascular events (MACE) and mortality is complex, because of heterogeneity in trial protocols and baseline characteristics of patients enrolled. Aim of this analysis is the exploration of possible determinants of heterogeneity of relative risk reduction for major cardiovascular events (MACE) and all-cause mortality. Incidence of events (MACE and mortality) in intervention and control groups and baseline characteristics of patients were extracted for each trial (EMPAREG, CANVAS, and DECLARE). For studies including both primary and secondary prevention cohorts, those two subgroups were considered separately. Metaregression analysis was used to assess the association of relative risk reduction with baseline characteristics of patients, including observed incidence of events with placebo. The estimated reduction in the incidence of MACE associated with SGLT-2 inhibitors showed a significant association with the incidence of MACE in the control group, suggesting that a greater effect was observed in trials enrolling patients at higher risk (Slope -0.008 [-0.023; 0.007], p = 0.31). A higher proportion of patients treated with statins, β-blockers and insulin at baseline was associated with a greater reduction of MACE, but not of mortality. In CVOT trials, the magnitude of the effect of SGLT-2 inhibitors on MACE is driven by absolute risk of enrolled patients; as a consequence, the estimated risk reduction is lower in primary prevention cohorts, which have a lower risk. This result supports the hypothesis of a class effect of SGLT-2 inhibitors on MACE.
Sections du résumé
BACKGROUND AND AIM
The interpretation of discrepancies across cardiovascular safety trials (CVOT) with SGLT-2 inhibitors in the incidence of major cardiovascular events (MACE) and mortality is complex, because of heterogeneity in trial protocols and baseline characteristics of patients enrolled. Aim of this analysis is the exploration of possible determinants of heterogeneity of relative risk reduction for major cardiovascular events (MACE) and all-cause mortality.
METHODS AND RESULTS
Incidence of events (MACE and mortality) in intervention and control groups and baseline characteristics of patients were extracted for each trial (EMPAREG, CANVAS, and DECLARE). For studies including both primary and secondary prevention cohorts, those two subgroups were considered separately. Metaregression analysis was used to assess the association of relative risk reduction with baseline characteristics of patients, including observed incidence of events with placebo. The estimated reduction in the incidence of MACE associated with SGLT-2 inhibitors showed a significant association with the incidence of MACE in the control group, suggesting that a greater effect was observed in trials enrolling patients at higher risk (Slope -0.008 [-0.023; 0.007], p = 0.31). A higher proportion of patients treated with statins, β-blockers and insulin at baseline was associated with a greater reduction of MACE, but not of mortality.
CONCLUSIONS
In CVOT trials, the magnitude of the effect of SGLT-2 inhibitors on MACE is driven by absolute risk of enrolled patients; as a consequence, the estimated risk reduction is lower in primary prevention cohorts, which have a lower risk. This result supports the hypothesis of a class effect of SGLT-2 inhibitors on MACE.
Identifiants
pubmed: 31757568
pii: S0939-4753(19)30286-8
doi: 10.1016/j.numecd.2019.07.018
pii:
doi:
Substances chimiques
Sodium-Glucose Transporter 2 Inhibitors
0
Types de publication
Journal Article
Meta-Analysis
Review
Langues
eng
Sous-ensembles de citation
IM
Pagination
71-76Informations de copyright
Copyright © 2019 The Italian Society of Diabetology, the Italian Society for the Study of Atherosclerosis, the Italian Society of Human Nutrition, and the Department of Clinical Medicine and Surgery, Federico II University. Published by Elsevier B.V. All rights reserved.