Dataset Information

Design and rationale of a multicentre, randomised, double-blind, placebo-controlled clinical trial to evaluate the effect of vitamin D on ventricular remodelling in patients with anterior myocardial infarction: the VITamin D in Acute Myocardial Infarction (VITDAMI) trial.

ABSTRACT:

Introduction

Decreased plasma vitamin D (VD) levels are linked to cardiovascular damage. However, clinical trials have not demonstrated a benefit of VD supplements on left ventricular (LV) remodelling. Anterior ST-elevation acute myocardial infarction (STEMI) is the best human model to study the effect of treatments on LV remodelling. We present a proof-of-concept study that aims to investigate whether VD improves LV remodelling in patients with anterior STEMI.

Methods and analysis

The VITamin D in Acute Myocardial Infarction (VITDAMI) trial is a multicentre, randomised, double-blind, placebo-controlled trial. 144 patients with anterior STEMI will be assigned to receive calcifediol 0.266 mg capsules (Hidroferol SGC)/15 days or placebo on a 2:1 basis during 12 months.

Primary objective

to evaluate the effect of calcifediol on LV remodelling defined as an increase in LV end-diastolic volume ≥10% (MRI).

Secondary objectives

change in LV end-diastolic and end-systolic volumes, ejection fraction, LV mass, diastolic function, sphericity index and size of fibrotic area; endothelial function; plasma levels of aminoterminal fragment of B-type natriuretic peptide, galectin-3 and monocyte chemoattractant protein-1; levels of calcidiol (VD metabolite) and other components of mineral metabolism (fibroblast growth factor-23 (FGF-23), the soluble form of its receptor klotho, parathormone and phosphate). Differences in the effect of VD will be investigated according to the plasma levels of FGF-23 and klotho. Treatment safety and tolerability will be assessed. This is the first study to evaluate the effect of VD on cardiac remodelling in patients with STEMI.

Ethics and dissemination

This trial has been approved by the corresponding Institutional Review Board (IRB) and National Competent Authority (Agencia Española de Medicamentos y Productos Sanitarios (AEMPS)). It will be conducted in accordance with good clinical practice (International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use - Good Clinical Practice (ICH-GCP)) requirements, ethical principles of the Declaration of Helsinki and national laws. The results will be submitted to indexed medical journals and national and international meetings.

Trial registration number

NCT02548364; Pre-results.

SUBMITTER: Tunon J

PROVIDER: S-EPMC4985833 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Publications

Design and rationale of a multicentre, randomised, double-blind, placebo-controlled clinical trial to evaluate the effect of vitamin D on ventricular remodelling in patients with anterior myocardial infarction: the VITamin D in Acute Myocardial Infarction (VITDAMI) trial.

Tuñón José J González-Hernández Ignacio I Llanos-Jiménez Lucía L Alonso-Martín Joaquín J Escudier-Villa Juan M JM Tarín Nieves N Cristóbal Carmen C Sanz Petra P Pello Ana M AM Aceña Álvaro Á Carda Rocío R Orejas Miguel M Tomás Marta M Beltrán Paula P Calero Rueda Marta M Marcos Esther E Serrano-Antolín José María JM Gutiérrez-Landaluce Carlos C Jiménez Rosa R Cabezudo Jorge J Curcio Alejandro A Peces-Barba Germán G González-Parra Emilio E Muñoz-Siscart Raquel R González-Casaus María Luisa ML Lorenzo Antonio A Huelmos Ana A Goicolea Javier J Ibáñez Borja B Hernández Gonzalo G Alonso-Pulpón Luis M LM Farré Jerónimo J Lorenzo Óscar Ó Mahíllo-Fernández Ignacio I Egido Jesús J

BMJ open 20160805 8

<h4>Introduction</h4>Decreased plasma vitamin D (VD) levels are linked to cardiovascular damage. However, clinical trials have not demonstrated a benefit of VD supplements on left ventricular (LV) remodelling. Anterior ST-elevation acute myocardial infarction (STEMI) is the best human model to study the effect of treatments on LV remodelling. We present a proof-of-concept study that aims to investigate whether VD improves LV remodelling in patients with anterior STEMI.<h4>Methods and analysis</h ...[more]

PMID: 27496232

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Project description:BackgroundThe role of cyclic guanosine 3',5'-monophosphate (cGMP) after acute myocardial infarction (AMI) is not well understood despite its significance as a second messenger of natriuretic peptides (NPs) in cardiovascular disease. We investigated the association between the NP-cGMP cascade and left ventricular reverse remodelling (LVRR) in anterior AMI.Methods67 patients with their first anterior AMI (median age, 64 years; male, 76%) underwent prospective evaluation of plasma concentrations of the molecular forms of A-type and B-type natriuretic peptide (BNP) and cGMP from immediately after primary percutaneous coronary intervention (PPCI) to 10 months post-AMI. The estimated mature BNP (emBNP) concentration was calculated as the difference between total BNP and prohormone of BNP (proBNP) concentrations. Patients were divided into LVRR and non-LVRR groups on the basis of residuals between observed change in left ventricular end-systolic volume index on MR during the first 11 months after AMI and change adjusted for proBNP concentration immediately post-PPCI, which was calculated with regression. The LVRR group (n=33) had residuals below the median; the non-LVRR group (n=34) had residuals at or above the median.ResultsThe LVRR group had higher freedom from major adverse cardiac and cerebrovascular events (MACCEs) than the non-LVRR group during a median follow-up of 9.9 years (p=0.008). The presence of LVRR (HR 0.256; 95% CI 0.081 to 0.809; p=0.028) and peak creatine phosphokinase-myocardial band level (per 100 IU/L) (HR 1.22; 95% CI 1.02 to 1.46; p=0.027) were independent predictors of MACCE after adjusting for age, male sex, infarct size and hypertension. Multivariable analyses identified logarithmic proBNP and emBNP concentrations from 12 hours to 5 days post-AMI and logarithmic cGMP concentration from immediately post-PPCI to 3 days post-AMI as independent predictors of LVRR (p<0.05).ConclusionsEarly-phase BNP-cGMP cascade activation might play a crucial role in LVRR in anterior AMI.

Project description:AimsLeft ventricular (LV) remodelling after acute myocardial infarction (AMI) is associated with heart failure and increased mortality. There was no consensus on the definition of LV remodelling, and the prognostic value of LV remodelling with different definitions has not been compared. We aimed to find the optimal definition and develop a prediction nomogram as well as online calculator that can identify patients at risk of LV remodelling.Methods and resultsThis prospective, observational study included 829 AMI patients undergoing percutaneous coronary intervention from January 2015 to January 2020. Echocardiography was performed within the 48 h of admission and at 6 months after infarction to evaluate LV remodelling, defined as a 20% increase in LV end-diastolic volume (LVEDV), a 15% increase in LV end-systolic volume (LVESV), or LV ejection fraction (LVEF) < 50% at 6 months. The impact of LV remodelling on long-term outcomes was analysed. Lasso regression was performed to screen potential predictors, and multivariable logistic regression analysis was conducted to establish the prediction nomogram. The area under the curve, calibration curve and decision curve analyses were used to determine the discrimination, calibration and clinical usefulness of the remodelling nomogram. The incidences of LV remodelling defined by LVEDV, LVESV and LVEF were 24.85% (n = 206), 28.71% (n = 238) and 14.60% (n = 121), respectively. Multivariable Cox regression models demonstrated that different definitions of LV remodelling were independently associated with the composite endpoint. However, only remodelling defined by LVEF was significantly connected with long-term mortality (hazard ratio = 2.78, 95% confidence interval 1.41-5.48, P = 0.003). Seven variables were selected to construct the remodelling nomogram, including diastolic blood pressure, heart rate, AMI type, stent length, N-terminal pro brain natriuretic peptide, troponin I, and glucose. The prediction model had an area under the receiver operating characteristics curve of 0.766. The calibration curve and decision curve analysis indicated consistency and better net benefit in the prediction model.ConclusionsLV remodelling defined by LVEDV, LVESV and LVEF were independent predictors for long-term mortality or heart failure hospitalization in AMI patients after percutaneous coronary intervention. However, only remodelling defined by LVEF was suitable for predicting all-cause death. In addition, the nomogram can provide an accurate and effective tool for the prediction of postinfarct remodelling.

Dataset Information

Design and rationale of a multicentre, randomised, double-blind, placebo-controlled clinical trial to evaluate the effect of vitamin D on ventricular remodelling in patients with anterior myocardial infarction: the VITamin D in Acute Myocardial Infarction (VITDAMI) trial.

Introduction

Methods and analysis

Primary objective

Secondary objectives

Ethics and dissemination

Trial registration number

Publications

Design and rationale of a multicentre, randomised, double-blind, placebo-controlled clinical trial to evaluate the effect of vitamin D on ventricular remodelling in patients with anterior myocardial infarction: the VITamin D in Acute Myocardial Infarction (VITDAMI) trial.

Similar Datasets

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