Dataset Information

Impact of chronic GLP-1 RA and SGLT-2I therapy on in-hospital outcome of diabetic patients with acute myocardial infarction.

ABSTRACT:

Background

Glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium glucose cotransporter-2 inhibitors (SGLT-2i) demonstrated cardiovascular and renal protection. Whether their benefits occur also during hospitalization for acute myocardial infarction (AMI) in patients with diabetes mellitus (DM) is not known. We evaluated in-hospital outcomes of patients hospitalized with AMI according to their chronic use of GLP-1 RA and/or SGLT-2i.

Methods

Using the health administrative databases of Lombardy, patients hospitalized with AMI from 2010 to 2019 were included. They were stratified according to DM status, then grouped into three cohorts using a propensity score matching: non-DM patients; DM patients treated with GLP-1 RA and/or SGLT-2i; DM patients not treated with GLP-1 RA/SGLT-2i. The primary endpoint of the study was the composite of in-hospital mortality, acute heart failure, and acute kidney injury requiring renal replacement therapy.

Results

We identified 146,798 patients hospitalized with AMI (mean age 71 ± 13 years, 34% females, 47% STEMI; 26% with DM). After matching, 3,090 AMI patients (1030 in each group) were included in the analysis. Overall, the primary endpoint rate was 16% (n = 502) and progressively increased from non-DM patients to DM patients treated with and without GLP-1 RA/SGLT-2i (13%, 16%, and 20%, respectively; P < 0.0001). Compared with non-DM patients, DM patients with GLP-1 RA/SGLT-2i had a 30% higher risk of the primary endpoint, while those not treated with GLP-1 RA/SGLT-2i had a 60% higher risk (P < 0.0001).

Conclusion

Chronic therapy with GLP-1 RA and/or SGLT-2i has a favorable impact on the clinical outcome of DM patients hospitalized with AMI.

SUBMITTER: Trombara F

PROVIDER: S-EPMC9903538 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Publications

Impact of chronic GLP-1 RA and SGLT-2I therapy on in-hospital outcome of diabetic patients with acute myocardial infarction.

Trombara Filippo F Cosentino Nicola N Bonomi Alice A Ludergnani Monica M Poggio Paolo P Gionti Luigia L Baviera Marta M Colacioppo Pierluca P Roncaglioni Maria Carla MC Leoni Olivia O Bortolan Francesco F Agostoni Piergiuseppe P Genovese Stefano S Marenzi Giancarlo G

Cardiovascular diabetology 20230206 1

<h4>Background</h4>Glucagon-like peptide-1 receptor agonists (GLP-1 RA) and sodium glucose cotransporter-2 inhibitors (SGLT-2i) demonstrated cardiovascular and renal protection. Whether their benefits occur also during hospitalization for acute myocardial infarction (AMI) in patients with diabetes mellitus (DM) is not known. We evaluated in-hospital outcomes of patients hospitalized with AMI according to their chronic use of GLP-1 RA and/or SGLT-2i.<h4>Methods</h4>Using the health administrative ...[more]

PMID: 36747186

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Project description:ImportanceNonalcoholic fatty liver disease (NAFLD) is a cardiovascular risk factor, but whether sodium-glucose cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) are associated with reduced cardiovascular risk in patients with type 2 diabetes (T2D) and concomitant NAFLD remains uncertain.ObjectiveTo investigate the outcomes of SGLT-2i and GLP-1RA therapy among patients with T2D varied by the presence or absence of NAFLD.Design, setting, and participantsThis retrospective, population-based, nationwide cohort study used an active-comparator new-user design. Two distinct new-user active-comparator cohorts of patients aged 40 years and older who initiated SGLT-2i or GLP-1RA were propensity score matched to patients who initiated dipeptidyl peptidase-4 inhibitors (DPP-4i). The study was conducted in South Korea from January 2013 to December 2020, and data analysis was conducted from October 2022 to March 2023.Main outcomes and measuresThe main outcomes were (1) major adverse cardiovascular events (MACE), a composite end point of hospitalization for myocardial infarction, hospitalization for stroke, and cardiovascular death, and (2) hospitalization for heart failure (HHF). Cox proportional hazards models were used to estimate hazard ratios (HRs). The Wald test was applied to assess heterogeneity by NAFLD.ResultsAfter 1:1 propensity score matching, 140 438 patients were retrieved in the first cohort (SGLT-2i vs DPP-4i; mean [SD] age, 57.5 [10.3] years; 79 633 [56.7%] male) and 34 886 patients were identified in the second cohort (GLP-1RA vs DPP-4i; mean [SD] age, 59.5 [10.5] years; 17 894 [51.3%] male). Compared with DPP-4i, SGLT-2i therapy was associated with a lower risk of MACE (HR, 0.78 [95% CI, 0.71-0.85]) and HHF (HR, 0.62 [95% CI, 0.48-0.81]). GLP-1RA therapy was associated with a decreased risk of MACE (HR, 0.49 [95% CI, 0.39-0.62]) but had statistically nonsignificant findings regarding HHF (HR, 0.64 [95% CI, 0.39-1.07]). Stratified analysis by NAFLD status yielded consistent results for SGLT-2i (MACE with NAFLD: HR, 0.73 [95% CI, 0.62-0.86]; without NAFLD: HR, 0.81 [95% CI, 0.72-0.91]; HHF with NAFLD: HR, 0.76 [95% CI, 0.49-1.17]; without NAFLD: HR, 0.56 [95% CI, 0.40-0.78]) and for GLP-1RA (MACE with NAFLD: HR, 0.49 [95% CI, 0.32-0.77]; without NAFLD: HR, 0.49 [95% CI, 0.37-0.65]; HHF with NAFLD: HR, 0.82 [95% CI, 0.38-1.76]; without NAFLD: HR, 0.54 [95% CI, 0.27-1.06]).Conclusions and relevanceIn this population-based cohort study, SGLT-2i therapy was associated with a decreased risk of MACE and HHF, while GLP-1RA therapy was associated with a decreased risk of MACE among patients with T2D, irrespective of baseline NAFLD status.

Project description:BackgroundFew studies explored the effect of the combination of glucose sodium-cotransporter-2 inhibitors (SGLT-2i) and glucagon-like peptide-1 receptor agonists (GLP-1RA) on the incidence of cardiovascular events in patients with type 2 diabetes (T2D) and acute myocardial infarction (AMI).MethodsWe recruited patients with T2D and AMI undergoing percutaneous coronary intervention, treated with either SGLT-2i or GLP-1RA for at least 3 months before hospitalization. Subjects with HbA1c < 7% at admission were considered in good glycemic control and maintained the same glucose-lowering regimen, while those with poor glycemic control (HbA1c ≥ 7%), at admission or during follow-up, were prescribed either a SGLT-2i or a GLP-1RA to obtain a SGLT-2i/GLP-1RA combination therapy. The primary outcome was the incidence of major adverse cardiovascular events (MACE) defined as cardiovascular death, re-acute coronary syndrome, and heart failure related to AMI during a 2-year follow-up. After 3 months, the myocardial salvage index (MSI) was assessed by single-photon emission computed tomography.FindingsOf the 537 subjects screened, 443 completed the follow-up. Of these, 99 were treated with SGLT-2i, 130 with GLP-1RA, and 214 with their combination. The incidence of MACE was lower in the combination therapy group compared with both SGLT-2i and GLP-1RA treated patients, as assessed by multivariable Cox regression analysis adjusted for cardiovascular risk factors (HR = 0.154, 95% CI 0.038-0.622, P = 0.009 vs GLP-1RA and HR = 0.170, 95% CI 0.046-0.633, P = 0.008 vs SGLT-2i). The MSI and the proportion of patients with MSI > 50% was higher in the SGLT-2i/GLP-1RA group compared with both SGLT-2i and GLP-1RA groups.InterpretationThe combination of SGLT-2i and GLP-1RA is associated with a reduced incidence of cardiovascular events in patients with T2D and AMI compared with either drug used alone, with a significant effect also on peri-infarcted myocardial rescue in patients without a second event. Trial registraition ClinicalTrials.gov ID: NCT06017544.

Project description:AimThe acute phase of myocardial infarction (MI) is accompanied by edema contributing to tissue damage and disease outcome. Here, we aimed to identify the mechanism whereby vascular endothelial growth factor (VEGF)-A induces myocardial edema in the acute phase of MI to eventually promote development of therapeutics to specifically suppress VEGFA-regulated vascular permeability while preserving collateral vessel formation.Methods and resultsVEGFA regulates vascular permeability and edema by activation of VEGF receptor-2 (VEGFR2), leading to induction of several signaling pathways including the cytoplasmic tyrosine kinase c-Src. The activated c-Src in turn phosphorylates vascular endothelial (VE)-cadherin, leading to dissociation of endothelial adherens junctions. A particular tyrosine at position 949 in mouse VEGFR2 has been shown to be required for activation of c-Src. Wild-type mice and mice with phenylalanine replacing tyrosine (Y) 949 in VEGFR2 (Vegfr2 Y949F/Y949F ) were challenged with MI through permanent ligation of the left anterior descending coronary artery. The infarct size was similar in wild-type and mutant mice, but left ventricular wall edema and fibrinogen deposition, indicative of vascular leakage, were reduced in the Vegfr2 Y949F/Y949F strain. When challenged with large infarcts, the Vegfr2 Y949F/Y949F mice survived significantly better than the wild-type strain. Moreover, neutrophil infiltration and levels of myeloperoxidase were low in the infarcted Vegfr2 Y949F/Y949F hearts, correlating with improved survival. In vivo tyrosine phosphorylation of VE-cadherin at Y685, implicated in regulation of vascular permeability, was induced by circulating VEGFA in the wild-type but remained at baseline levels in the Vegfr2 Y949F/Y949F hearts.ConclusionSuppression of VEGFA/VEGFR2-regulated vascular permeability leads to diminished edema without affecting vascular density correlating with improved myocardial parameters and survival after MI.

Dataset Information

Impact of chronic GLP-1 RA and SGLT-2I therapy on in-hospital outcome of diabetic patients with acute myocardial infarction.

Background

Methods

Results

Conclusion

Publications

Impact of chronic GLP-1 RA and SGLT-2I therapy on in-hospital outcome of diabetic patients with acute myocardial infarction.

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