Summary
Background
Improvements in the treatment of coronary artery disease mean that an increasing number of patients survive acute cardiovascular events and live as outpatients with or without anginal symptoms.
Aim
To determine the characteristics and management of contemporary outpatients with stable coronary artery disease in Western Europe, and to compare France with the other Western European countries.
Methods
CLARIFY (prospeCtive observational LongitudinAl RegIstry oF patients with stable coronary arterY disease) is an international, prospective, observational, longitudinal study. Between November 2009 and July 2010, 32,954 adult outpatients with stable coronary artery disease (defined as a history of documented myocardial infarction [of > 3 months], prior coronary revascularization, chest pain with myocardial ischaemia, or coronary stenosis of > 50% proven by angiography) were enrolled in 45 countries. The demographics and management of CLARIFY patients enrolled in France were compared with those enrolled in other Western European countries (Austria, Belgium, Denmark, Germany, Greece, Ireland, Italy, Netherlands, Portugal, Spain, Switzerland and the UK).
Results
Of the 14,726 patients enrolled in Western Europe (mean age 66.2 [10.2] years; 79.6% male), 2432 (16.5%) were from France. The use of aspirin was lower in France than in other Western European countries (74.5% vs. 86.9%, respectively), whereas use of thienopyridines (48.5% vs. 21.7%), oral anticoagulants (12.3% vs. 9.0%) and lipid-lowering drugs (95.8% vs. 92.5%) was higher. Beta-blockers were used in 73% of both groups. Angina was less prevalent in France (6.3% vs. 15.5%) and French patients showed higher levels of physical activity than their counterparts in Western Europe.
Conclusions
The management of patients with stable CAD in France appears favourable, with good adherence to guideline-based therapies, but there remains room for improvement in terms of symptom and risk factor control.
Résumé
Contexte
Les améliorations dans le traitement de la maladie coronaire impliquent qu’un nombre croissant de patients survivent après un événement coronaire aigu et deviennent des patients ambulatoires avec ou sans symptômes angineux.
Objectif
Déterminer les caractéristiques et la prise en charge des patients ambulatoires porteurs d’une maladie coronaire stable en Europe de l’Ouest et comparer les patients français avec les patients des autres pays européens.
Méthodes
CLARIFY (ProspeCtive observational LongitudinAl RegIstry oF patients with stable coronary arterY disease) est une étude internationale longitudinale prospective et observationnelle. Entre novembre 2009 et juillet 2010, 32 954 patients adultes porteurs d’une maladie coronaire stable (définie comme des patients ayant une histoire d’infarctus du myocarde documenté de plus de 3 mois, un antécédent de revascularisation coronaire, des douleurs thoraciques avec une ischémie myocardique ou une sténose coronaire de plus de 50 % démontrée par une coronarographie) ont été inclus dans 45 pays. Les caractéristiques démographiques et la prise en charge des patients CLARIFY inclus en France ont été comparés avec celles des patients inclus dans les autres pays d’Europe de l’Ouest (Autriche, Belgique, Danemark, Allemagne, Grèce, Irlande, Italie, Pays-Bas, Portugal, Espagne, Suisse et le Royaume-Uni).
Résultats
Parmi les 14 726 patients inclus en Europe de l’Ouest (moyenne d’âge : 66,2 [10,2] ans ; 79,6 % d’hommes), 2432 (16,5 %) étaient des patients français. L’utilisation d’aspirine était plus basse en France que dans les autres pays européens de l’Ouest (74,5 % vs 86,9 %, respectivement) tandis que l’utilisation des thiénopyridines (48,1 % vs 21,7 %), les anticoagulants oraux (12,3 % vs 9,0 %) et les traitements hypolipidémiants (95,8 % vs 92,5 %) étaient plus élevés. Les bêtabloqueurs étaient utilisés chez 73 % des patients des deux groupes. L’angine de poitrine était moins prévalente en France (6,3 % vs 15,5 %) et les patients français présentaient un plus haut niveau d’activité physique par rapport aux autres patients d’Europe de l’Ouest.
Conclusion
La prise en charge des patients porteurs d’une maladie coronaire stable en France semble appropriée, avec une bonne adhésion aux thérapeutiques recommandées, mais il reste des améliorations à faire afin de contrôler les symptômes et les facteurs de risque.
Introduction
Despite substantial improvements in preventive cardiology, coronary artery disease (CAD) remains the leading cause of death and morbidity worldwide and in Europe . Secondary prevention of acute coronary syndromes has also advanced, with a series of large, randomized clinical trials establishing the value of antiplatelet therapy, statins, and angiotensin-converting enzyme inhibitors in this setting . CAD places a major burden on public health , due not only to an ageing population, but also to the increasing numbers of patients who survive an initial acute cardiovascular event and live as outpatients, with or without anginal symptoms , and who are at high risk of myocardial infarction, heart failure, arrhythmia, and death. Important determinants of long-term CAD survival include risk factors and their management, including left ventricular function, extent of artery disease, heart rate , and treatment .
Important changes in the management and outcomes of patients with CAD mean that a need has arisen for current data in patients with stable CAD treated in everyday practice. It is important to have longitudinal observations of a large, representative cohort of patients, spanning several geographical regions, focusing on stable outpatients, and including both symptomatic and asymptomatic individuals. The prospeCtive observational LongitudinAl RegIstry oF patients with stable coronary arterY disease (CLARIFY) was initiated to improve our knowledge about the contemporary stable CAD population . The aim of this analysis was to compare the characteristics and management of CLARIFY patients from France with those from patients in other Western European countries.
Methods
Study design
CLARIFY is an international, prospective, observational, longitudinal registry in outpatients with stable CAD, followed up for 5 years. The study rationale and methods have been published previously . Patients were enrolled between November 2009 and July 2010 in 45 countries in Africa, Asia, Australia, Europe, the Middle East, and North, Central and South America.
The registry is being performed in accordance with the principles of the Declaration of Helsinki and has been approved by local institutional review boards. All patients gave written informed consent to participate in agreement with national and local guidelines. Patient confidentiality is ensured by the use of patient identification code numbers that correspond to computer files. As an observational study, the management and treatment of patients is conducted according to usual practices, with no specific tests or therapies defined in the study protocol.
Study population
Eligible subjects were outpatients with stable CAD demonstrated by a history of at least one of the following criteria: documented myocardial infarction (> 3 months previously); coronary stenosis > 50% proven by coronary angiography; chest pain with myocardial ischaemia proven by stress electrocardiogram, stress echocardiography, or myocardial imaging; or coronary artery bypass graft or percutaneous coronary intervention performed > 3 months previously.
Patients were excluded from participation if they had been hospitalized for cardiovascular disease within the previous 3 months (including for revascularization), were planned to undergo revascularization, or had a condition expected to hamper participation up to 5 years (e.g. limited cooperation or legal capacity, serious non-cardiovascular disease, a condition that could affect life expectancy [e.g. cancer, drug abuse], or severe cardiovascular disease [e.g. advanced heart failure, severe valve disease, history of valve repair/replacement]).
Evaluations
Baseline data were collected anonymously using electronic case report forms. Information documented included patient demographics, medical history, risk factors, employment status, the results of physical examination, heart rate (determined by both pulse palpation and 12-lead electrocardiography, using the most recent electrocardiogram within 6 months in clinically stable patients), laboratory values (if available), and current chronic medical treatments (i.e. taken regularly for ≥ 7 days before entry into the registry).
Study setting and site selection
To ensure that the population was representative of the real-life community of stable CAD outpatients, recruitment of sites and patients was based on the predefined selection of physician types and consecutive enrolment of eligible patients. In each country participating in CLARIFY, the types (office-based primary care physicians, internists, physicians based in hospitals with outpatient clinics, cardiologists, or other specialties) and practice settings (hospital-based as opposed to ambulatory practice) of physicians in charge of CAD patients was determined, using the best available epidemiological data and market research data. This allowed targeting of an appropriate proportion of each of these physician types and settings, and provided a distribution of physicians (and therefore of patient populations) across regions and locations (urban, suburban, or rural) that reflected the epidemiological patterns in each country. The national coordinator in each country also reviewed the site selection. Each physician recruited, over a brief period of time, 10–15 outpatients with stable CAD.
Data management and quality
Data were collected centrally using a standardized, international case report form (translated into the local language) and sent by each country to the data management centre (Robertson Centre for Biostatistics, University of Glasgow, UK) where checks for completeness, internal consistency, and accuracy were run. Data quality control is performed annually onsite in 1% of randomly selected sites up to 5 years. At these sites, 100% of case report forms for patients enrolled at that site were monitored for source documentation and accuracy. Data quality control was done at face-to-face quality control visits, and involved review of source documents supporting the adequacy and accuracy of data collected on the case report forms.
In this analysis, the data from patients enrolled in France were compared with those enrolled in the other Western European countries participating in CLARIFY (Austria, Belgium, Denmark, Germany, Greece, Ireland, Italy, Netherlands, Portugal, Spain, Switzerland, UK).
Statistical analysis
Data were analysed by an independent statistics centre at the Robertson Centre for Biostatistics. Baseline variables are summarized as mean (standard deviation) or median (interquartile range) for continuous data, depending on the distribution of the data, and as counts and percentages for categorical data, and were based on patients in whom data were available. Comparisons between patients in France and those in Western Europe were made using one-way ANOVA or the Kruskal-Wallis test for continuous variables, again depending on the distribution of the data, and Pearson’s Chi 2 test or Fisher’s exact test for categorical variables. All analyses were performed using SAS version 9.2. A significance level of 0.05 was used to test for statistical differences; all tests used were two-sided.
Results
Study population
Of the 33,428 outpatients screened, 18,702 were excluded from the present analysis for one of the following reasons: 101 did not provide written informed consent, 42 did not meet the inclusion or exclusion criteria, in 331 patients informed consent or institutional review board approval was not ascertained or verifiable, and 18,228 patients were enrolled outside of Western Europe. Of the remaining 14,726 patients, 12,294 were from Western Europe (excluding France) and 2432 were from France ( Fig. 1 ). Patient enrolment in France took place between May and July 2010.
The mean age of the Western European population was 66.2 (10.2) years and 79.6% were male. The baseline characteristics of the outpatients, classified according to enrolment in France or other Western European country, are detailed in Table 1 . French patients were, on average, more frequently male (83.7% vs. 78.8%) and slightly older (66.7 vs. 66.1 years), and had a lower mean heart rate (64.6 vs. 66.5 beats per minute [bpm] on palpation) and higher left ventricular ejection fraction (59.3% vs. 56.9%) than patients in other Western European countries. French patients were less likely than those in other Western European countries to have treated hypertension (57.7% vs. 69.8%), to have a family history of premature CAD (24.7% vs. 29.6%) or to have congestive heart failure (2.9% vs. 7.9%), but were more likely to have dyslipidaemia (79.6% vs. 76.0%). A minority of patients achieved low-density lipoprotein cholesterol concentrations of < 1.8 mmol/L (< 70 mg/dL) (18.4% in France vs. 20.1% in other Western European countries). French patients also had a less frequent history of myocardial infarction (53.8% vs. 57.9%) and stroke (2.4% vs. 3.5%), but were more likely to have peripheral artery disease (17.6% vs. 11.5%). They were also more likely to have undergone a previous percutaneous coronary intervention (72.5% vs. 59.6%), whereas coronary artery bypass grafting was less frequently performed (22.6% vs. 26.7%). French patients showed higher levels of physical activity.
| Parameter | Patients with data | France ( n = 2432) | Europe ( n = 12,294) | P -value |
|---|---|---|---|---|
| Age (y), mean (SD) | 14,701 | 66.7 (10.7) | 66.1 (10.0) | 0.0057 |
| Men, n (%) | 14,703 | 2031 (83.7) | 9675 (78.8) | < 0.0001 |
| BMI (kg/m 2 ), median (IQR) | 14,691 | 26.8 (24.5, 29.7) | 27.7 (25.4, 30.5) | < 0.0001 |
| Risk factors | ||||
| Diabetes mellitus, n (%) | 14,705 | 619 (25.5) | 3272 (26.6) | 0.25 |
| Dyslipidaemia, n (%) | 14,707 | 1930 (79.6) | 9333 (76.0) | 0.0001 |
| Family history of CAD a , n (%) | 14,707 | 600 (24.7) | 3634 (29.6) | < 0.0001 |
| Treated hypertension, n (%) | 14,707 | 1400 (57.7) | 8578 (69.8) | < 0.0001 |
| Presentation characteristics | ||||
| HR palpation (bpm), mean (SD) | 14,679 | 64.6 (9.9) | 66.5 (10.6) | < 0.0001 |
| HR ECG (bpm), mean (SD) | 11,564 | 63.5 (10.2) | 65.9 (11.3) | < 0.0001 |
| SBP (mmHg), mean (SD) | 14,686 | 131.3 (14.1) | 131.5 (16.4) | 0.75 |
| DBP (mmHg), mean (SD) | 14,686 | 75.5 (8.4) | 76.6 (9.5) | < 0.0001 |
| Controlled blood pressure (SBP < 140/DBP < 90 mmHg) | 14,686 | 1658 (68.9) | 7903 (64.4) | < 0.0001 |
| LVEF (%), mean (SD) | 10,234 | 59.3 (10.1) | 56.9 (10.8) | < 0.0001 |
| Creatinine (mmol/L), median (IQR) | 11,146 | 0.09 (0.08, 0.10) | 0.09 (0.08, 0.10) | 0.96 |
| Total cholesterol (mmol/L), median (IQR) | 11,678 | 4.3 (3.8, 4.9) | 4.3 (3.7, 4.9) | 0.21 |
| LDL-cholesterol | 10,005 | 2.3 (2.0, 2.8) | 2.4 (1.9, 2.9) | 0.08 |
| LDL, n (%) | 10,005 | |||
| < 70 mg/dL (< 1.82 mmol/L) | 364 (18.4) | 1611 (20.1) | < 0.0001 | |
| 70–100 mg/dL (1.82–2.60 mmol/L) | 925 (46.8) | 3323 (41.4) | ||
| > 100 mg/dL (> 2.60 mmol/L) | 688 (34.8) | 3094 (38.5) | ||
| High-density lipoprotein cholesterol | 10,884 | 1.2 (1.0, 1.5) | 1.2 (1.0, 1.4) | <0.0001 |
| CHF symptoms including NYHA class, n (%) | 14,704 | |||
| No CHF | 2352 (97.1) | 11,313 (92.1) | < 0.0001 | |
| Class II | 53 (2.2) | 813 (6.6) | ||
| Class III | 18 (0.7) | 155 (1.3) | ||
| Current evidence of myocardial ischaemia, n (%) | 14,692 | 300 (12.4) | 2277 (18.6) | < 0.0001 |
| Medical history | ||||
| Peripheral artery disease, n (%) | 14,706 | 426 (17.6) | 1408 (11.5) | < 0.0001 |
| Myocardial infarction, n (%) | 14,706 | 1304 (53.8) | 7114 (57.9) | 0.0002 |
| Stroke, n (%) | 14,706 | 59 (2.4) | 428 (3.5) | 0.0081 |
| PCI, n (%) | 14,707 | 1758 (72.5) | 7322 (59.6) | < 0.0001 |
| CABG, n (%) | 14,707 | 547 (22.6) | 3277 (26.7) | < 0.0001 |
| Pacemaker, n (%) | 14,707 | 94 (3.9) | 365 (3.0) | 0.019 |
| Hospitalization for CHF, n (%) | 14,707 | 111 (4.6) | 464 (3.8) | 0.06 |
| Atrial fibrillation/flutter, n (%) | 14,707 | 209 (8.6) | 1041 (8.5) | 0.82 |
| Asthma/COPD, n (%) | 14,707 | 217 (8.9) | 1185 (9.6) | 0.28 |
| Reimbursement of cardiovascular agents, n (%) | 14,665 | |||
| Fully reimbursed | 2359 (97.8) | 6684 (54.5) | < 0.0001 | |
| Partly reimbursed | 51 (2.1) | 4281 (34.9) | ||
| Not reimbursed | 1 (0.04) | 1289 (10.5) | ||
| Lifestyle characteristics | ||||
| Smoking status, n (%) | 14,708 | |||
| Current | 250 (10.3) | 1428 (11.6) | 0.12 | |
| Former | 1221 (50.4) | 6207 (50.5) | ||
| Never | 954 (39.3) | 4648 (37.8) | ||
| Alcohol intake (number of drinks per week), n (%) | 14,706 | |||
| 0 | 836 (34.5) | 4118 (33.5) | 0.61 | |
| > 0 and < 20 | 1469 (60.6) | 7528 (61.3) | ||
| ≥ 20 | 119 (4.9) | 636 (5.2) | ||
| Stimulant drinks consumed, n (%) | 14,705 | |||
| Coffee | 1550 (64.0) | 7204 (58.7) | < 0.0001 | |
| Tea | 187 (7.7) | 2442 (19.9) | ||
| Neither | 686 (28.3) | 2636 (21.5) | ||
| Physical activity, n (%) | 14,703 | |||
| None | 353 (14.6) | 2194 (17.9) | < 0.0001 | |
| Light physical activity most weeks | 969 (40.0) | 6126 (49.9) | ||
| ≥ 20 min vigorous physical activity 1–2 times/week | 583 (24.1) | 2116 (17.2) | ||
| ≥ 20 min vigorous physical activity ≥ 3 times/week | 516 (21.3) | 1846 (15.0) | ||
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