Predictors for major cardiovascular outcomes in stable ischaemic heart disease (PREMAC): statistical analysis plan for data originating from the CLARICOR (clarithromycin for patients with stable coronary heart disease) trial
Abstract Background The purpose of the predictors for major cardiovascular outcomes in stable ischaemic heart disease (PREMAC) study is exploratory and hypothesis generating. We want to identify biochemical quantities which—conditionally on the values of available standard demographic, anamnestic, a...
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2017-03-01
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Series: | Diagnostic and Prognostic Research |
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Online Access: | http://link.springer.com/article/10.1186/s41512-017-0009-y |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Per Winkel Janus Christian Jakobsen Jørgen Hilden Theis Lange Gorm Boje Jensen Erik Kjøller Ahmad Sajadieh Jens Kastrup Hans Jørn Kolmos Anders Larsson Johan Ärnlöv Christian Gluud |
spellingShingle |
Per Winkel Janus Christian Jakobsen Jørgen Hilden Theis Lange Gorm Boje Jensen Erik Kjøller Ahmad Sajadieh Jens Kastrup Hans Jørn Kolmos Anders Larsson Johan Ärnlöv Christian Gluud Predictors for major cardiovascular outcomes in stable ischaemic heart disease (PREMAC): statistical analysis plan for data originating from the CLARICOR (clarithromycin for patients with stable coronary heart disease) trial Diagnostic and Prognostic Research CLARICOR Ischaemic heart disease Predictors Biomarkers Mortality |
author_facet |
Per Winkel Janus Christian Jakobsen Jørgen Hilden Theis Lange Gorm Boje Jensen Erik Kjøller Ahmad Sajadieh Jens Kastrup Hans Jørn Kolmos Anders Larsson Johan Ärnlöv Christian Gluud |
author_sort |
Per Winkel |
title |
Predictors for major cardiovascular outcomes in stable ischaemic heart disease (PREMAC): statistical analysis plan for data originating from the CLARICOR (clarithromycin for patients with stable coronary heart disease) trial |
title_short |
Predictors for major cardiovascular outcomes in stable ischaemic heart disease (PREMAC): statistical analysis plan for data originating from the CLARICOR (clarithromycin for patients with stable coronary heart disease) trial |
title_full |
Predictors for major cardiovascular outcomes in stable ischaemic heart disease (PREMAC): statistical analysis plan for data originating from the CLARICOR (clarithromycin for patients with stable coronary heart disease) trial |
title_fullStr |
Predictors for major cardiovascular outcomes in stable ischaemic heart disease (PREMAC): statistical analysis plan for data originating from the CLARICOR (clarithromycin for patients with stable coronary heart disease) trial |
title_full_unstemmed |
Predictors for major cardiovascular outcomes in stable ischaemic heart disease (PREMAC): statistical analysis plan for data originating from the CLARICOR (clarithromycin for patients with stable coronary heart disease) trial |
title_sort |
predictors for major cardiovascular outcomes in stable ischaemic heart disease (premac): statistical analysis plan for data originating from the claricor (clarithromycin for patients with stable coronary heart disease) trial |
publisher |
BMC |
series |
Diagnostic and Prognostic Research |
issn |
2397-7523 |
publishDate |
2017-03-01 |
description |
Abstract Background The purpose of the predictors for major cardiovascular outcomes in stable ischaemic heart disease (PREMAC) study is exploratory and hypothesis generating. We want to identify biochemical quantities which—conditionally on the values of available standard demographic, anamnestic, and biochemical data—may improve the prediction of cardiovascular outcomes and/or death in patients suffering from stable ischaemic heart disease. The candidate biochemical quantities include N-terminal pro-B-type natriuretic peptide, YKL-40, osteoprotegerin, high-sensitive assay cardiac troponin T (hs-cTnT), pregnancy-associated plasma protein-A (PAPP-A), cathepsin B, cathepsin S, soluble TNF receptor 1 and 2, neutrophil gelatinase-associated lipocalin, endostatin, and calprotectin. As an extra objective, we also want to assess if skewness in these predictors may explain why the clarithromycin for patients with stable coronary heart disease (CLARICOR) trial found increased all-cause and cardiovascular (CV) mortality on a brief clarithromycin regimen compared with placebo. Methods Baseline data were obtained from the hospital files at five cardiology clinics covering the Copenhagen area. The CLARICOR trial included data from 4372 stable coronary artery disease patients recruited among such patients alive and diagnosed with acute myocardial infarction or unstable angina pectoris during 1993 to 1999 in Copenhagen and randomised during October 1999 to April 2000 to the CLARICOR trial of 14 days clarithromycin versus placebo. Initial follow-up lasted for 2.6 years, during which outcomes were collected through hospital and death registries and assessed by an adjudication committee. Corresponding register data later showed to produce similar results. The adjudicated outcomes were therefore replaced and augmented by register data on outcomes to cover 10 years of follow-up. Biochemical marker data were obtained from analysis of serum from the CLARICOR bio-bank collected at randomisation and stored at −80° C. Using Cox proportional hazard method, we will identify among the candidate biochemical quantities those which are significant predictors when used alone and in combination with the standard predictors as defined in the present study. Discussion Patients who became stable during the period 1993 to 1999 and died before October 1999 are missing. The data from the placebo patients are nevertheless useful to identify new prognostic biomarkers in patients with stable coronary artery disease, and data from both trial groups are useful to assess important potential skewness between randomised groups. However, due to the potential selection bias, we do not feel that it is advisable to try to rank identified biochemical predictors relative to each other nor to use the results for predictive purposes. Trial registration ClinicalTrials.gov, NCT00121550 Date of registration 13 July 2005 Date of enrolment of first participant 12 October 1999 |
topic |
CLARICOR Ischaemic heart disease Predictors Biomarkers Mortality |
url |
http://link.springer.com/article/10.1186/s41512-017-0009-y |
work_keys_str_mv |
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doaj-f08c82144fff4f30bc2bd940d8bcebb92020-11-24T21:05:42ZengBMCDiagnostic and Prognostic Research2397-75232017-03-01111810.1186/s41512-017-0009-yPredictors for major cardiovascular outcomes in stable ischaemic heart disease (PREMAC): statistical analysis plan for data originating from the CLARICOR (clarithromycin for patients with stable coronary heart disease) trialPer Winkel0Janus Christian Jakobsen1Jørgen Hilden2Theis Lange3Gorm Boje Jensen4Erik Kjøller5Ahmad Sajadieh6Jens Kastrup7Hans Jørn Kolmos8Anders Larsson9Johan Ärnlöv10Christian Gluud11Copenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Blegdamsvej 9, Rigshospitalet, Copenhagen University HospitalCopenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Blegdamsvej 9, Rigshospitalet, Copenhagen University HospitalSection of Biostatistics, Department of Public Health, University of CopenhagenSection of Biostatistics, Department of Public Health, University of CopenhagenDepartment of Cardiology, Hvidovre Hospital, Copenhagen University HospitalDepartment of Cardiology S, Herlev Hospital, Copenhagen University HospitalDepartment of Cardiology, Bispebjerg Hospital, Copenhagen University HospitalDepartment of Cardiology B, The Heart Centre, Rigshospitalet, Copenhagen University HospitalDepartment of Clinical Microbiology, Odense University HospitalDepartment of Neurobiology, Care Sciences and Society/Division of Family Medicine, Karolinska InstituteDepartment of Neurobiology, Care Sciences and Society/Division of Family Medicine, Karolinska InstituteCopenhagen Trial Unit, Centre for Clinical Intervention Research, Department 7812, Blegdamsvej 9, Rigshospitalet, Copenhagen University HospitalAbstract Background The purpose of the predictors for major cardiovascular outcomes in stable ischaemic heart disease (PREMAC) study is exploratory and hypothesis generating. We want to identify biochemical quantities which—conditionally on the values of available standard demographic, anamnestic, and biochemical data—may improve the prediction of cardiovascular outcomes and/or death in patients suffering from stable ischaemic heart disease. The candidate biochemical quantities include N-terminal pro-B-type natriuretic peptide, YKL-40, osteoprotegerin, high-sensitive assay cardiac troponin T (hs-cTnT), pregnancy-associated plasma protein-A (PAPP-A), cathepsin B, cathepsin S, soluble TNF receptor 1 and 2, neutrophil gelatinase-associated lipocalin, endostatin, and calprotectin. As an extra objective, we also want to assess if skewness in these predictors may explain why the clarithromycin for patients with stable coronary heart disease (CLARICOR) trial found increased all-cause and cardiovascular (CV) mortality on a brief clarithromycin regimen compared with placebo. Methods Baseline data were obtained from the hospital files at five cardiology clinics covering the Copenhagen area. The CLARICOR trial included data from 4372 stable coronary artery disease patients recruited among such patients alive and diagnosed with acute myocardial infarction or unstable angina pectoris during 1993 to 1999 in Copenhagen and randomised during October 1999 to April 2000 to the CLARICOR trial of 14 days clarithromycin versus placebo. Initial follow-up lasted for 2.6 years, during which outcomes were collected through hospital and death registries and assessed by an adjudication committee. Corresponding register data later showed to produce similar results. The adjudicated outcomes were therefore replaced and augmented by register data on outcomes to cover 10 years of follow-up. Biochemical marker data were obtained from analysis of serum from the CLARICOR bio-bank collected at randomisation and stored at −80° C. Using Cox proportional hazard method, we will identify among the candidate biochemical quantities those which are significant predictors when used alone and in combination with the standard predictors as defined in the present study. Discussion Patients who became stable during the period 1993 to 1999 and died before October 1999 are missing. The data from the placebo patients are nevertheless useful to identify new prognostic biomarkers in patients with stable coronary artery disease, and data from both trial groups are useful to assess important potential skewness between randomised groups. However, due to the potential selection bias, we do not feel that it is advisable to try to rank identified biochemical predictors relative to each other nor to use the results for predictive purposes. Trial registration ClinicalTrials.gov, NCT00121550 Date of registration 13 July 2005 Date of enrolment of first participant 12 October 1999http://link.springer.com/article/10.1186/s41512-017-0009-yCLARICORIschaemic heart diseasePredictorsBiomarkersMortality |