XML Template (2014) [6.6.2014–9:11am] //blrnas3/cenpro/ApplicationFiles/Journals/SAGE/3B2/CPRJ/Vol00000/140076/APPFile/SG-CPRJ140076.3d
(CPR)
[1–8] [PREPRINTER stage]
EURO PEAN SO CIETY O F CARDIOLOGY ®
Original scientific paper
Secondary medical prevention and clinical outcome in coronary artery disease patients with a history of non-coronary vascular intervention: A report from the CORONOR investigators
European Journal of Preventive Cardiology 0(00) 1–8 ! The European Society of Cardiology 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/2047487314538857 ejpc.sagepub.com
Pascal Delsart1, Gilles Lemesle1,2,3, Nicolas Lamblin1,2,3, Olivier Tricot4, Thibaud Meurice5, Christophe Mycinski6, Mariam Elkohen7, Akram Chmait8, Ste´phan Haulon1,3,9 and Christophe Bauters1,2,3
Abstract Aim: To assess the level of secondary prevention and the outcome of coronary artery disease (CAD) in patients who have a history of non-coronary vascular intervention. Background: Patients with polyvascular disease have been reported to receive less evidence-based medications, with worse risk factor control and to be at higher risk than patients with single-bed disease. It is unknown whether these findings remain valid in the modern era of secondary prevention. Methods: We included 4184 patients with stable CAD. Two groups were formed according to the absence (n ¼ 3704) or presence (n ¼ 480) of a history of non-coronary vascular intervention. Treatments and risk factor control were recorded at inclusion. Follow-up was performed after 2 years. Results: Antiplatelets, angiotensin system antagonists, beta-blockers and statins were widely prescribed in both groups. The number of antihypertensive drugs was higher in patients with non-coronary vascular intervention. Except for slight increases in the rate of current smokers and in systolic blood pressure, risk factor control was similar between groups. All-cause and cardiovascular mortality rates were higher in patients with non-coronary intervention with adjusted HR of 1.55 (1.13–2.13) (p ¼ 0.007), and 1.98 (1.24–3.15) (p ¼ 0.004), respectively. Conclusions: In modern practice and real life conditions, the higher risk of CAD patients with a history of noncoronary vascular intervention is taken into account, with more intense secondary prevention and similar risk factor control than patients without such history. In spite of the level of secondary prevention, patients with a history of noncoronary vascular intervention remain at high risk of cardiovascular events. This should be an incentive to discuss more stringent objectives for secondary prevention in patients with polyvascular disease.
Keywords Coronary artery disease, peripheral vascular disease, secondary prevention, risk factors, prognosis Received 9 February 2014; accepted 18 May 2014
1
Centre Hospitalier Re´gional et Universitaire de Lille, Lille, France Inserm U744, Institut Pasteur de Lille, Universite´ Lille Nord de France, Lille, France 3 Faculte´ de Me´decine de Lille, Lille, France 4 Centre Hospitalier de Dunkerque, Dunkerque, France 5 Polyclinique du Bois, Lille, France 6 Centre Hospitalier de Be´thune, Be´thune, France 2
7
Hoˆpital Prive´ de Villeneuve d’Ascq, Villeneuve d’Ascq, France Clinique de la Coˆte d’Opale, Boulogne-Sur-Mer, France 9 Inserm U1008, Universite´ Lille Nord de France, Lille, France 8
Corresponding author: Christophe Bauters, Hoˆpital Cardiologique, CHRU de Lille, Boul Prof Leclercq, 59037 Lille Cedex, France. Email: [email protected]
Downloaded from cpr.sagepub.com at Selcuk Universitesi on January 28, 2015
XML Template (2014) [6.6.2014–9:11am] //blrnas3/cenpro/ApplicationFiles/Journals/SAGE/3B2/CPRJ/Vol00000/140076/APPFile/SG-CPRJ140076.3d
(CPR)
[1–8] [PREPRINTER stage]
2
European Journal of Preventive Cardiology 0(00)
Introduction
Study design and follow-up
Coronary artery disease (CAD) is a major public health problem.1 Although there has been important progress in the treatment of CAD, the association with other manifestations of vascular disease identifies a subgroup that has consistently been associated with higher mortality and morbidity rates in the literature.2–4 A frequent explanation for this observation is that patients with polyvascular disease may have a greater atherosclerotic burden and consequently a higher risk of cardiovascular events. However, other factors may also play a major role, and particularly the under-treatment and poor risk factor control, which has been repeatedly demonstrated for peripheral artery disease patients.5,6 As a consequence, current guidelines suggest that the coexistence of CAD with other manifestations of vascular disease should prompt closer attention with strict control of risk factors and the use of preventive treatments.7 In recent years, there have been reports of improvements in secondary prevention in CAD populations.8–12 This progress has also affected the high-risk subgroup with polyvascular disease, but whether this has had an impact on prognosis is not known. We therefore designed the present study with two specific aims. Firstly, to assess, in a recent cohort of patients with stable CAD, if a history of non-coronary vascular intervention – as an indicator of polyvascular disease – is still associated with inadequate secondary prevention. And, secondly, to determine how the achieved level of secondary prevention translates in terms of clinical outcome during follow-up when compared with patients with CAD as the sole manifestation of atherosclerosis.
A case record form, which contained information regarding demographic and clinical details of the patients including usual cardiovascular risk factors and treatments, was prospectively completed at the initial visit. The presence of other vascular disease was not prospectively assessed at inclusion but the history of non-coronary vascular intervention (NCVI) was recorded in the case record form. The study population (n ¼ 4184) was therefore divided into two separate groups according to the absence (n ¼ 3704) or presence (n ¼ 480) of a history of NCVI (aortic surgery for aneurysm or dissection (n ¼ 48), aortic endoprosthesis for aneurysm or dissection (n ¼ 32), open surgery for peripheral artery disease (n ¼ 116), percutaneous intervention for peripheral artery disease (n ¼ 264) or carotid endarterectomy (n ¼ 121)). Two-year clinical follow-up was performed at outpatient visits or by contacting the general practitioner. We collected data on death, MI and stroke. All clinical events were adjudicated blindly by two investigators and by three investigators in case of disagreement. The cause of death was determined after a detailed review of the circumstances of death and classified as cardiovascular, non cardiovascular or unknown.
Methods Study population The CORONOR study was a multicentre study that enrolled 4184 consecutive outpatients with stable CAD between February 2010 and April 2011.10 Patients were considered eligible if they had evidence of CAD defined by at least one of the following: previous myocardial infarction (MI) (more than 1 year ago), previous coronary revascularization (more than 1 year ago), and/or obstruction of 50% of the luminal diameter of at least one native vessel on coronary angiography. The sole exclusion criterion was hospitalization for MI or coronary revascularization within the last year. In order to present the real life spectrum of stable CAD, patients with other cardiovascular or non-cardiovascular illnesses or comorbidities were not excluded.
Statistical analysis Continuous variables were described as mean standard deviation or as median with 25th and 75th percentiles. Variables with skewed distribution were log-transformed before use as continuous variables in statistical analyses. Categorical variables were presented as absolute numbers and percentages. Baseline characteristics, cardiovascular treatments and risk factor control were compared with the 2 test or the Fisher test for categorical variables and the Student unpaired t-test for continuous variables as appropriate. Cumulative event rates were estimated using the Kaplan-Meier method and compared using the log rank test. Cox proportional hazard analyses were performed to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Age, gender, time since CAD diagnosis, smoking, history of hypertension, diabetes mellitus, prior MI, multivessel CAD, prior coronary bypass, left ventricular ejection fraction and estimated glomerular filtration rate were included as covariates. For each variable, the proportional hazards assumption was tested visually using Kaplan-Meier curves and by examining a plot of ln [ln(survival time)] against the ln(time). In addition, the proportional hazard was assessed and satisfied by including an interaction time-dependent term in the multivariable Cox regression analysis. All statistical analyses were
Downloaded from cpr.sagepub.com at Selcuk Universitesi on January 28, 2015
XML Template (2014) [6.6.2014–9:11am] //blrnas3/cenpro/ApplicationFiles/Journals/SAGE/3B2/CPRJ/Vol00000/140076/APPFile/SG-CPRJ140076.3d
(CPR)
[1–8] [PREPRINTER stage]
Delsart et al.
3
performed with the STATA 9.2 softwareÕ (STATA Corporation, College Station, Texas, USA). Statistical significance was assumed at p-value
(CPR)
[1–8] [PREPRINTER stage]
EURO PEAN SO CIETY O F CARDIOLOGY ®
Original scientific paper
Secondary medical prevention and clinical outcome in coronary artery disease patients with a history of non-coronary vascular intervention: A report from the CORONOR investigators
European Journal of Preventive Cardiology 0(00) 1–8 ! The European Society of Cardiology 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/2047487314538857 ejpc.sagepub.com
Pascal Delsart1, Gilles Lemesle1,2,3, Nicolas Lamblin1,2,3, Olivier Tricot4, Thibaud Meurice5, Christophe Mycinski6, Mariam Elkohen7, Akram Chmait8, Ste´phan Haulon1,3,9 and Christophe Bauters1,2,3
Abstract Aim: To assess the level of secondary prevention and the outcome of coronary artery disease (CAD) in patients who have a history of non-coronary vascular intervention. Background: Patients with polyvascular disease have been reported to receive less evidence-based medications, with worse risk factor control and to be at higher risk than patients with single-bed disease. It is unknown whether these findings remain valid in the modern era of secondary prevention. Methods: We included 4184 patients with stable CAD. Two groups were formed according to the absence (n ¼ 3704) or presence (n ¼ 480) of a history of non-coronary vascular intervention. Treatments and risk factor control were recorded at inclusion. Follow-up was performed after 2 years. Results: Antiplatelets, angiotensin system antagonists, beta-blockers and statins were widely prescribed in both groups. The number of antihypertensive drugs was higher in patients with non-coronary vascular intervention. Except for slight increases in the rate of current smokers and in systolic blood pressure, risk factor control was similar between groups. All-cause and cardiovascular mortality rates were higher in patients with non-coronary intervention with adjusted HR of 1.55 (1.13–2.13) (p ¼ 0.007), and 1.98 (1.24–3.15) (p ¼ 0.004), respectively. Conclusions: In modern practice and real life conditions, the higher risk of CAD patients with a history of noncoronary vascular intervention is taken into account, with more intense secondary prevention and similar risk factor control than patients without such history. In spite of the level of secondary prevention, patients with a history of noncoronary vascular intervention remain at high risk of cardiovascular events. This should be an incentive to discuss more stringent objectives for secondary prevention in patients with polyvascular disease.
Keywords Coronary artery disease, peripheral vascular disease, secondary prevention, risk factors, prognosis Received 9 February 2014; accepted 18 May 2014
1
Centre Hospitalier Re´gional et Universitaire de Lille, Lille, France Inserm U744, Institut Pasteur de Lille, Universite´ Lille Nord de France, Lille, France 3 Faculte´ de Me´decine de Lille, Lille, France 4 Centre Hospitalier de Dunkerque, Dunkerque, France 5 Polyclinique du Bois, Lille, France 6 Centre Hospitalier de Be´thune, Be´thune, France 2
7
Hoˆpital Prive´ de Villeneuve d’Ascq, Villeneuve d’Ascq, France Clinique de la Coˆte d’Opale, Boulogne-Sur-Mer, France 9 Inserm U1008, Universite´ Lille Nord de France, Lille, France 8
Corresponding author: Christophe Bauters, Hoˆpital Cardiologique, CHRU de Lille, Boul Prof Leclercq, 59037 Lille Cedex, France. Email: [email protected]
Downloaded from cpr.sagepub.com at Selcuk Universitesi on January 28, 2015
XML Template (2014) [6.6.2014–9:11am] //blrnas3/cenpro/ApplicationFiles/Journals/SAGE/3B2/CPRJ/Vol00000/140076/APPFile/SG-CPRJ140076.3d
(CPR)
[1–8] [PREPRINTER stage]
2
European Journal of Preventive Cardiology 0(00)
Introduction
Study design and follow-up
Coronary artery disease (CAD) is a major public health problem.1 Although there has been important progress in the treatment of CAD, the association with other manifestations of vascular disease identifies a subgroup that has consistently been associated with higher mortality and morbidity rates in the literature.2–4 A frequent explanation for this observation is that patients with polyvascular disease may have a greater atherosclerotic burden and consequently a higher risk of cardiovascular events. However, other factors may also play a major role, and particularly the under-treatment and poor risk factor control, which has been repeatedly demonstrated for peripheral artery disease patients.5,6 As a consequence, current guidelines suggest that the coexistence of CAD with other manifestations of vascular disease should prompt closer attention with strict control of risk factors and the use of preventive treatments.7 In recent years, there have been reports of improvements in secondary prevention in CAD populations.8–12 This progress has also affected the high-risk subgroup with polyvascular disease, but whether this has had an impact on prognosis is not known. We therefore designed the present study with two specific aims. Firstly, to assess, in a recent cohort of patients with stable CAD, if a history of non-coronary vascular intervention – as an indicator of polyvascular disease – is still associated with inadequate secondary prevention. And, secondly, to determine how the achieved level of secondary prevention translates in terms of clinical outcome during follow-up when compared with patients with CAD as the sole manifestation of atherosclerosis.
A case record form, which contained information regarding demographic and clinical details of the patients including usual cardiovascular risk factors and treatments, was prospectively completed at the initial visit. The presence of other vascular disease was not prospectively assessed at inclusion but the history of non-coronary vascular intervention (NCVI) was recorded in the case record form. The study population (n ¼ 4184) was therefore divided into two separate groups according to the absence (n ¼ 3704) or presence (n ¼ 480) of a history of NCVI (aortic surgery for aneurysm or dissection (n ¼ 48), aortic endoprosthesis for aneurysm or dissection (n ¼ 32), open surgery for peripheral artery disease (n ¼ 116), percutaneous intervention for peripheral artery disease (n ¼ 264) or carotid endarterectomy (n ¼ 121)). Two-year clinical follow-up was performed at outpatient visits or by contacting the general practitioner. We collected data on death, MI and stroke. All clinical events were adjudicated blindly by two investigators and by three investigators in case of disagreement. The cause of death was determined after a detailed review of the circumstances of death and classified as cardiovascular, non cardiovascular or unknown.
Methods Study population The CORONOR study was a multicentre study that enrolled 4184 consecutive outpatients with stable CAD between February 2010 and April 2011.10 Patients were considered eligible if they had evidence of CAD defined by at least one of the following: previous myocardial infarction (MI) (more than 1 year ago), previous coronary revascularization (more than 1 year ago), and/or obstruction of 50% of the luminal diameter of at least one native vessel on coronary angiography. The sole exclusion criterion was hospitalization for MI or coronary revascularization within the last year. In order to present the real life spectrum of stable CAD, patients with other cardiovascular or non-cardiovascular illnesses or comorbidities were not excluded.
Statistical analysis Continuous variables were described as mean standard deviation or as median with 25th and 75th percentiles. Variables with skewed distribution were log-transformed before use as continuous variables in statistical analyses. Categorical variables were presented as absolute numbers and percentages. Baseline characteristics, cardiovascular treatments and risk factor control were compared with the 2 test or the Fisher test for categorical variables and the Student unpaired t-test for continuous variables as appropriate. Cumulative event rates were estimated using the Kaplan-Meier method and compared using the log rank test. Cox proportional hazard analyses were performed to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). Age, gender, time since CAD diagnosis, smoking, history of hypertension, diabetes mellitus, prior MI, multivessel CAD, prior coronary bypass, left ventricular ejection fraction and estimated glomerular filtration rate were included as covariates. For each variable, the proportional hazards assumption was tested visually using Kaplan-Meier curves and by examining a plot of ln [ln(survival time)] against the ln(time). In addition, the proportional hazard was assessed and satisfied by including an interaction time-dependent term in the multivariable Cox regression analysis. All statistical analyses were
Downloaded from cpr.sagepub.com at Selcuk Universitesi on January 28, 2015
XML Template (2014) [6.6.2014–9:11am] //blrnas3/cenpro/ApplicationFiles/Journals/SAGE/3B2/CPRJ/Vol00000/140076/APPFile/SG-CPRJ140076.3d
(CPR)
[1–8] [PREPRINTER stage]
Delsart et al.
3
performed with the STATA 9.2 softwareÕ (STATA Corporation, College Station, Texas, USA). Statistical significance was assumed at p-value
