Dataset Information

Adding liraglutide to the backbone therapy of biguanide in patients with coronary artery disease and newly diagnosed type-2 diabetes (the AddHope2 study): a randomised controlled study protocol.

ABSTRACT:

Introduction

Newly diagnosed type 2 diabetes mellitus (T2DM) in patients with coronary artery disease (CAD) more than doubles the risk of death compared with otherwise matched glucose tolerant patients. The biguanide metformin is the drug of choice in treatment of T2DM and has shown to ameliorate cardiovascular morbidity in patients with T2DM and myocardial infarction (MI). The incretin hormone, glucagon-like peptide-1 (GLP-1) improves β-cell function, insulin sensitivity and causes weight loss and has been suggested to have beneficial effects on cardiac function. The GLP-1 receptor agonist (GLP-1RA), liraglutide, is currently used for treatment of T2DM but its potential effect on cardiac function has not been investigated in detail. We hypothesised that liraglutide added to metformin backbone therapy in patients with CAD and newly diagnosed T2DM will improve β-cell function and left ventricular systolic function during dobutamine stress.

Methods and analyses

40 patients with CAD and newly diagnosed T2DM will receive the intervention liraglutide+metformin and placebo+metformin in this investigator-initiated, double blind, randomised, placebo-controlled, cross-over 12 plus 12 weeks intervention study with a 2-week washout period. The primary cardiovascular end point is changes in left ventricular ejection fraction during stress echocardiography. The primary endocrine end point is β-cell function evaluated during a frequently sampled intravenous glucose tolerance test. Secondary end points include heart rate variability, diurnal blood pressure, glucagon suppression and inflammatory response (urine, blood and adipose tissue).

Ethics and dissemination

This study is approved by the Danish Medicines Agency, the Danish Dataprotection Agency and the Regional Committee on Biomedical Research Ethics of the Capital Region of Denmark. The trial will be carried out under the guidance from the GCP unit at Copenhagen University Hospital of Bispebjerg and in accordance with the ICH-GCP guidelines and the Helsinki Declaration.

Trial registrations number

Clinicaltrials.gov ID: NCT01595789, EudraCT: 2011-005405-78.

SUBMITTER: Anholm C

PROVIDER: S-EPMC4401817 | biostudies-literature | 2014 Jul

REPOSITORIES: biostudies-literature

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Publications

Adding liraglutide to the backbone therapy of biguanide in patients with coronary artery disease and newly diagnosed type-2 diabetes (the AddHope2 study): a randomised controlled study protocol.

Anholm Christian C Kumarathurai Preman P Klit Malene S MS Kristiansen Ole P OP Nielsen Olav W OW Ladelund Steen S Madsbad Sten S Sajadieh Ahmad A Haugaard Steen B SB

BMJ open 20140716 7

<h4>Introduction</h4>Newly diagnosed type 2 diabetes mellitus (T2DM) in patients with coronary artery disease (CAD) more than doubles the risk of death compared with otherwise matched glucose tolerant patients. The biguanide metformin is the drug of choice in treatment of T2DM and has shown to ameliorate cardiovascular morbidity in patients with T2DM and myocardial infarction (MI). The incretin hormone, glucagon-like peptide-1 (GLP-1) improves β-cell function, insulin sensitivity and causes weig ...[more]

PMID: 25031198

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Project description:Background: Epidemiological characteristics and prognostic profiles of patients with newly diagnosed coronary artery disease (CAD) are heterogeneous. Therefore, providing individualized cardiovascular (CV) risk stratification and tailored prevention is crucial. Objective: Phenotypic unsupervised clustering integrating clinical, coronary computed tomography angiography (CCTA), and cardiac magnetic resonance (CMR) data were used to unveil pathophysiological differences between subgroups of patients with newly diagnosed CAD. Materials and Methods: Between 2008 and 2020, consecutive patients with newly diagnosed obstructive CAD on CCTA and further referred for vasodilator stress CMR were followed for the occurrence of major adverse cardiovascular events (MACE), defined by cardiovascular death or non-fatal myocardial infarction. For this exploratory work, a cluster analysis was performed on clinical, CCTA, and CMR variables, and associations between phenogroups and outcomes were assessed. Results: Among 2,210 patients who underwent both CCTA and CMR, 2,015 (46% men, mean 70 ± 12 years) completed follow-up [median 6.8 (IQR 5.9-9.2) years], in which 277 experienced a MACE (13.7%). Three mutually exclusive and clinically distinct phenogroups (PG) were identified based upon unsupervised hierarchical clustering of principal components: (PG1) CAD in elderly patients with few traditional risk factors; (PG2) women with metabolic syndrome, calcified plaques on CCTA, and preserved left ventricular ejection fraction (LVEF); (PG3) younger men smokers with proximal non-calcified plaques on CCTA, myocardial scar, and reduced LVEF. Using survival analysis, the occurrence of MACE, cardiovascular mortality, and all-cause mortality (all p < 0.001) differed among the three PG, in which PG3 had the worse prognosis. In each PG, inducible ischemia was associated with MACE [PG1, Hazards Ratio (HR) = 3.09, 95% CI, 1.70-5.62; PG2, HR = 3.62, 95% CI, 2.31-5.7; PG3, HR = 3.55, 95% CI, 2.3-5.49; all p < 0.001]. The study presented some key limitations that may impact generalizability. Conclusions: Cluster analysis of clinical, CCTA, and CMR variables identified three phenogroups of patients with newly diagnosed CAD that were associated with distinct clinical and prognostic profiles. Inducible ischemia assessed by stress CMR remained associated with the occurrence of MACE within each phenogroup. Whether automated unsupervised phenogrouping of CAD patients may improve clinical decision-making should be further explored in prospective studies.

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Dataset Information

Adding liraglutide to the backbone therapy of biguanide in patients with coronary artery disease and newly diagnosed type-2 diabetes (the AddHope2 study): a randomised controlled study protocol.

Introduction

Methods and analyses

Ethics and dissemination

Trial registrations number

Publications

Adding liraglutide to the backbone therapy of biguanide in patients with coronary artery disease and newly diagnosed type-2 diabetes (the AddHope2 study): a randomised controlled study protocol.

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