Effect of empagliflozin on total myocardial infarction events by type and additional coronary outcomes: insights from the randomized EMPA-REG OUTCOME trial.


Journal

Cardiovascular diabetology
ISSN: 1475-2840
Titre abrégé: Cardiovasc Diabetol
Pays: England
ID NLM: 101147637

Informations de publication

Date de publication:
11 Jul 2024
Historique:
received: 07 03 2024
accepted: 19 06 2024
medline: 12 7 2024
pubmed: 12 7 2024
entrez: 11 7 2024
Statut: epublish

Résumé

The effect of empagliflozin, a sodium-glucose-co-transporter-2 inhibitor, on risk for myocardial infarction has not been fully characterized. This study comprised prespecified and post-hoc analyses of the EMPA-REG OUTCOME trial in which 7020 people with type 2 diabetes (T2D) and cardiovascular disease [mostly atherosclerotic (ASCVD)] were randomized to empagliflozin or placebo and followed for a median 3.1 years. We assessed the effect of empagliflozin on total (first plus recurrent) events of centrally adjudicated fatal and non-fatal myocardial infarction (MI) using a negative binomial model with robust confidence intervals (CI) that preserves randomization and accounts for the within-patient correlation of multiple events. Post hoc, we analyzed types of MI: type 1 (related to plaque-rupture/thrombus), type 2 (myocardial supply-demand imbalance), type 3 (sudden-death related, i.e. fatal MI), type 4 (percutaneous coronary intervention-related), and type 5 (coronary artery bypass graft-related). MIs could be assigned to > 1 type. There were 421 total MIs (including recurrent); 299, 86, 26, 19, and 1 were classified as type 1, 2, 3, 4, and 5 events, respectively. Overall, empagliflozin reduced the risk of total MI events by 21% [rate ratio for empagliflozin vs. placebo, 0.79 (95% CI, 0.620-0.998), P = 0.0486], largely driven by its effect on type 1 [rate ratio, 0.79 (95% CI, 0.61-1.04)] and type 2 MIs [rate ratio, 0.67 (95% CI, 0.41-1.10)]. In T2D patients with ASCVD, empagliflozin reduced the risk of MIs, with consistent effects across the two most common etiologies, i.e. type 1 and 2. URL: https://www. gov ; Unique identifier: NCT01131676.

Sections du résumé

BACKGROUND BACKGROUND
The effect of empagliflozin, a sodium-glucose-co-transporter-2 inhibitor, on risk for myocardial infarction has not been fully characterized.
METHODS METHODS
This study comprised prespecified and post-hoc analyses of the EMPA-REG OUTCOME trial in which 7020 people with type 2 diabetes (T2D) and cardiovascular disease [mostly atherosclerotic (ASCVD)] were randomized to empagliflozin or placebo and followed for a median 3.1 years. We assessed the effect of empagliflozin on total (first plus recurrent) events of centrally adjudicated fatal and non-fatal myocardial infarction (MI) using a negative binomial model with robust confidence intervals (CI) that preserves randomization and accounts for the within-patient correlation of multiple events. Post hoc, we analyzed types of MI: type 1 (related to plaque-rupture/thrombus), type 2 (myocardial supply-demand imbalance), type 3 (sudden-death related, i.e. fatal MI), type 4 (percutaneous coronary intervention-related), and type 5 (coronary artery bypass graft-related). MIs could be assigned to > 1 type.
RESULTS RESULTS
There were 421 total MIs (including recurrent); 299, 86, 26, 19, and 1 were classified as type 1, 2, 3, 4, and 5 events, respectively. Overall, empagliflozin reduced the risk of total MI events by 21% [rate ratio for empagliflozin vs. placebo, 0.79 (95% CI, 0.620-0.998), P = 0.0486], largely driven by its effect on type 1 [rate ratio, 0.79 (95% CI, 0.61-1.04)] and type 2 MIs [rate ratio, 0.67 (95% CI, 0.41-1.10)].
CONCLUSIONS CONCLUSIONS
In T2D patients with ASCVD, empagliflozin reduced the risk of MIs, with consistent effects across the two most common etiologies, i.e. type 1 and 2.
TRAIL REGISTRATION BACKGROUND
URL: https://www.
CLINICALTRIALS RESULTS
gov ; Unique identifier: NCT01131676.

Identifiants

pubmed: 38992713
doi: 10.1186/s12933-024-02328-6
pii: 10.1186/s12933-024-02328-6
doi:

Substances chimiques

empagliflozin HDC1R2M35U
Glucosides 0
Benzhydryl Compounds 0
Sodium-Glucose Transporter 2 Inhibitors 0

Banques de données

ClinicalTrials.gov
['NCT01131676']

Types de publication

Journal Article Randomized Controlled Trial Multicenter Study

Langues

eng

Sous-ensembles de citation

IM

Pagination

248

Informations de copyright

© 2024. The Author(s).

Références

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Auteurs

David Fitchett (D)

Division of Cardiology, St Michael's Hospital, University of Toronto, Toronto, ON, Canada.

Bernard Zinman (B)

Lunenfeld-Tanenbaum Research Institute, Mount Sinai Hospital, University of Toronto, Toronto, ON, Canada.

Silvio E Inzucchi (SE)

Section of Endocrinology, Yale University School of Medicine, New Haven, CT, USA.

Christoph Wanner (C)

Würzburg University Clinic, Würzburg, Germany.

Stefan D Anker (SD)

Department of Cardiology (CVK) and Berlin Institute of Health Center for Regenerative Therapies (BCRT), German Centre for Cardiovascular Research (DZHK) Partner Site Berlin, Charité Universitätsmedizin Berlin, Berlin, Germany.
Institute of Heart Diseases, Wrocław Medical University, Wrocław, Poland.

Stuart Pocock (S)

Department of Medical Statistics, London School of Hygiene & Tropical Medicine, London, UK.

Michaela Mattheus (M)

Boehringer Ingelheim Pharma GmbH & Co. KG, Ingelheim, Germany.

Ola Vedin (O)

Boehringer Ingelheim AB, Stockholm, Sweden.

Søren S Lund (SS)

Boehringer Ingelheim International GmbH, Ingelheim, Germany. soeren.lund@boehringer-ingelheim.com.

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