Summary
Background
European guidelines recommend a low-density lipoprotein cholesterol (LDL-C) target of < 1.8 mmol/L (70 mg/dL), and/or a ≥ 50% reduction when the target level cannot be reached, for patients at very high cardiovascular risk, and high-potency lipid-lowering therapy (LLT) in patients with an acute coronary syndrome (ACS).
Aim
To document the prevalence of lipid abnormalities and the achievement of lipid targets among patients surviving an ACS and in patients with stable coronary heart disease (CHD), using data from the DYSIS II study.
Methods
DYSIS II was an observational cross-sectional study conducted in 21 countries (2012–2014). We report data from the French cohort, comprising patients hospitalized with an ACS and patients diagnosed with stable CHD. Data on patient characteristics, risk factors, treatments and lipid profile were collected. LDL-C target achievement was assessed based on the European guidelines endorsed by the French Society of Cardiology.
Results
Of the 468 ACS patients, 277 (59.2%) were receiving LLT at admission to hospital; 22.6% were hospitalized for a recurrent event. Statins were used in 96.6% (450/466) of patients at discharge and in 95.1% (310/326) at 120-day follow-up, at which time 50.6% (80/158) of patients with available data achieved the LDL-C goal. Most of the 436 patients with stable CHD (97.2%) were on LLT (56.8% on high-intensity therapy); 29.2% of patients on LLT met the LDL-C treatment target < 1.8 mmol/L (70 mg/dL).
Conclusion
These observational data show the progress made in the treatment of ACS from the acute phase up to 3 months, and highlight key areas for improvement in the prevention of recurrent events in patients with CHD in France. The use of higher intensity or combination LLT as recommended in secondary prevention are needed to increase the achievement of LDL-C treatment targets and reduce the risk of morbidity and mortality due to CHD.
Résumé
Contexte
Les recommandations européennes préconisent un objectif pour le cholestérol des lipoprotéines de basse densité (LDL-C) inférieur à 1,8 mmol/L (70 mg/dL), et/ou ≥ 50 % de réduction de LDL-C lorsque l’objectif ne peut pas être atteint, pour les patients à très haut risque cardiovasculaire, avec des traitements hypolipidémiants de forte intensité pour les patients avec un syndrome coronarien aigu (SCA)
Objectif
Documenter la prévalence des anomalies lipidiques et l’atteinte des objectifs lipidiques parmi les patients après un SCA ainsi que parmi les patients avec une maladie coronaire (MC) stable en utilisant les données de l’étude DYSIS II.
Méthodes
DYSIS II était une étude observationnelle transversale menée dans les 21 pays (2012–2014). Nous rapportons les données de la cohorte française, comprenant les patients hospitalisés avec un SCA et les patients avec une MC stable. Les données sur les caractéristiques des patients, les facteurs de risque, le traitement et le profil lipidique ont été collectées. L’atteinte des objectifs lipidiques a été déterminée selon les recommandations européennes validées par la Société française de cardiologie.
Résultats
Parmi les 468 patients avec un SCA, 277 (59,2 %) recevaient de traitement hypolipidémiant à l’admission à hôpital ; 22,6 % ont été hospitalisés à la suite d’un événement coronarien récurrent. Les statines étaient utilisées chez 96,6 % (450/466) des patients à la sortie de l’hospitalisation et chez 95,1 % (310/326) lors du suivi à 120 jours ; lors de ce suivi, 50,6 % (80/158) des patients pour lesquels les données étaient disponibles avaient atteint les objectifs de LDL-C. La majorité des 436 patients avec MC stable (97,2 %) recevaient un traitement hypolipidémiant (56,8 % des traitements de forte intensité) ; 29,2 % de patients sous traitement avaient atteint l’objectif de LDL-C inférieur à 1,8 mmol/L (70 mg/dL).
Conclusion
Ces données observationnelles montrent les progrès obtenus dans la prise en charge en aigu et lors du suivi à 3 mois après l’événement et soulignent les possibilités d’amélioration de la prise en charge et de la prévention des événements récurrents chez les patients avec une maladie coronaire en France. L’intensification des traitements en prévention secondaire par une augmentation des doses ou des associations médicamenteuses est nécessaire afin d’améliorer l’atteinte des objectifs lipidiques et réduire le risque de morbi-mortalité coronaire.
Background
Hypercholesterolemia is a major contributor to the development of atherosclerosis and coronary heart disease (CHD), with all-cause mortality rising in association with increasing concentrations of low-density lipoprotein cholesterol (LDL-C) . A large prospective meta-analysis involving over 90,000 individuals, almost half of whom had pre-existing CHD, showed that every 1 mmol/L reduction in LDL-C achieved with statin therapy resulted in a 21% reduction in major vascular events . Guidelines from the European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) recommend an LDL-C target of < 1.8 mmol/L (70 mg/dL), and/or a ≥ 50% reduction from baseline when this target cannot be reached, for patients at very high cardiovascular risk, and the administration of high-potency statin therapy as the first choice in patients presenting with an acute coronary syndrome (ACS) . Not all patients achieve these lipid goals, and require the addition of a non-statin lipid-lowering therapy (LLT) such as ezetimibe, while others are intolerant of statin therapy . Ezetimibe, when combined with a statin, results in an additional 20–25% reduction in LDL-C compared with statin monotherapy . The recently published IMPROVE-IT trial also demonstrated that ezetimibe, on top of statin therapy, improved cardiovascular outcomes .
In a previous examination of the first 12 countries (11 European countries and Canada) included in the DYSIS study , conducted between April 2008 and February 2009, half of the 22,063 statin-treated patients age ≥ 45 years did not achieve their therapeutic LDL-C goal, highlighting a gap between evidence-based recommendations and clinical practice. Among the patients enrolled in France, only 39.6% achieved the target lipid values . We sought to document the prevalence of lipid abnormalities and the achievement of lipid targets among patients who have had an ACS and in patients with stable CHD in France, using data from the global Dyslipidemia International Study (DYSIS) II ACS/CHD study.
Methods
Study design and population
DYSIS II was a cross-sectional observational study conducted in 21 countries in Asia-Pacific, Europe and Middle East/Africa between 2012 and 2014. Two distinct patient populations were enrolled: those hospitalized with an ACS (DYSIS II ACS) and those diagnosed with stable CHD (DYSIS II CHD). The study design is shown in Fig. 1 .
Patients who were eligible for enrolment in DYSIS II ACS were:
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≥ 18 years of age;
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had been hospitalized for an ACS (ST-segment elevation myocardial infarction, left bundle branch block, non-ST-segment elevation myocardial infarction or unstable angina) at the time of enrolment;
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had a full lipid profile performed on blood drawn within 24 hours of admission;
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had either been on LLT for ≥ 3 months or were not taking any LLT.
Patients were given a booklet at enrolment and instructed to take it with them when they next visited their physician following discharge from the index event. The booklet was retained by the patient and was completed by their physician during subsequent consultations, capturing the patient’s lipid profile and other basic characteristics. The purpose of the booklet was to gather accurate information that could be reported by the patient during the follow-up telephone interview, which was carried out with patients (or their next of kin) 120 ± 15 days after the index event.
DYSIS II CHD enrolled patients ≥ 18 years of age with stable CHD during a single visit to their physician on an outpatient basis. Physicians were representative of the general population of clinicians managing patients for secondary prevention in France, and included general practitioners or family physicians, internists and cardiologists. Stable CHD was defined as one or more of the following:
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> 50% stenosis on coronary angiography or computed tomography;
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previous percutaneous coronary intervention; previous coronary artery bypass graft;
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history of ACS > 3 months previously.
Patients were required to have had a fasting lipid profile done within the previous 12 months, either while on LLT for ≥ 3 months or not on any LLT. Patients with a history of ACS within the previous 3 months were not eligible for enrolment in DYSIS CHD.
To avoid selection bias, centres participating in DYSIS II were strongly encouraged to enrol all consecutive patients who fulfilled the inclusion criteria. Patients enrolled in clinical trials involving medication were not eligible.
Data on patient characteristics, risk factors, treatments (LLT and selected concomitant pharmacological therapies) and laboratory values were collected using an electronic case report form. LDL-C target achievement was assessed based on the 2011 ESC/EAS guidelines for patients at very high cardiovascular risk (LDL-C < 1.8 mmol/L [70 mg/dL]) .
DYSIS II was strictly observational in nature and the protocol did not recommend or discourage any treatments, procedures, diagnostics or examinations that were not part of those delivered in routine medical care. As such, the study served to comprehensively document current secondary prevention practices in patients with CHD or ACS, regardless of current treatment.
This study was conducted in accordance with good epidemiological and clinical practice, and all applicable laws, rules and regulations, and was approved by the authorities in all participating countries. All subjects provided written informed consent to participate.
Objectives
The primary objective in the French cohort of this observational study was to document real-life lipid concentrations relative to the targets in the 2011 ESC/EAS guidelines for the management of dyslipidaemias in patients hospitalized with an ACS and in those with stable CHD, who had either been on LLT for ≥ 3 months or were not taking any LLT. Key secondary objectives were to describe the patient characteristics and risk profiles, to document drug usage patterns and to determine lipid goal achievements.
Study management
A site management team (Institut für Herzinfarktforschung Ludwigshafen, Ludwigshafen, Germany) was responsible for training the site personnel on all aspects of the study and was a resource for data-collection questions and query resolution. This team closely monitored patient enrolment and data submission at each site and performed calls, as necessary, to stimulate enrolment or data submission.
Standardized data management procedures were undertaken to ensure the integrity and analytical utility of the study data, including handling rules for missing or incomplete data, range checks and data transformations. Data quality checks were carried out at the time of data entry and before creation of the analysis dataset. Data were anonymized to protect patient confidentiality. Source documentation and data accuracy were verified in 25% of cases.
Statistical analysis
Categorical variables are described using count (percentage) and continuous quantitative variables as mean ± standard deviation (SD) or median (interquartile range [IQR]). Treatment patterns, healthcare usage patterns, and all other documented variables were compared among prespecified subgroups using the chi-square test or Mann-Whitney-Wilcoxon test, as appropriate. In all analyses, a value of P ≤ 0.05 was considered statistically significant. All analyses were performed using SAS software version 9.3 (Cary, NC, USA).
Results
DYSIS II ACS
DYSIS II ACS was conducted in 24 coronary care units in France. Of the 468 patients enrolled, half (50.6%) had ST-segment elevation myocardial infarction or left bundle branch block, 40.8% had non-ST-segment elevation myocardial infarction, and 8.5% had unstable angina ( Table 1 ). The mean age of the ACS population was 65 ± 12 years and 80.1% were men. More than one-fifth (22.6%) had been hospitalized for a recurrent ischaemic event; these patients had a more severe medical history, including a higher prevalence of chronic kidney disease, type 2 diabetes mellitus, and peripheral artery disease, than patients with a first (incident) ACS, and 90.6% were on LLT compared with 50.0% of those with an incident ACS. Patients with an incident ACS who were receiving LLT were older than those not on LLT and had a more severe medical history ( Table 1 ).
| Variable | ACS | Stable CHD | ||||||
|---|---|---|---|---|---|---|---|---|
| All ACS | Incident ACS ( n = 362) | Recurrent ACS ( n = 106) | All CHD | No LLT | LLT | |||
| ( n = 468) | ( n = 436) | ( n = 12) | ( n = 424) | |||||
| No LLT ( n = 181) | LLT ( n = 181) | No LLT ( n = 10) | LLT ( n = 96) | |||||
| Age (years) | 65 ± 12 | 60 ± 12 | 68 ± 11 | 69 ± 11 | 65 ± 13 | 69 ± 12 | 74 ± 12 | 69 ± 12 |
| Men | 375 (80.1) | 154 (85.1) | 134 (74.0) | 5 (50.0) | 82 (85.4) | 349 (80.0) | 11 (91.7) | 338 (79.7) |
| Systolic BP (mmHg) | 138 ± 24 | 140 ± 26 | 139 ± 24 | 133 ± 19 | 135 ± 23 | 132 ± 13 | 134 ± 13 | 132 ± 13 |
| Diastolic BP (mmHg) | 80 ± 16 | 82 ± 16 | 80 ± 16 | 73 ± 14 | 75 ± 13 | 76 ± 9 | 82 ± 7 | 76 ± 9 |
| Medical history | ||||||||
| Myocardial infarction | 106 (22.6) | 0 | 0 | 10 (100) | 96 (100) | 236/435 (54.3) | 7 (58.3) | 229/423 (54.1) |
| CKD | 18 (3.8) | 5 (2.8) | 6 (3.3) | 2 (20.0) | 5 (5.2) | 22 (5.0) | 0 | 22 (5.2) |
| Diabetes mellitus type 2 a | 102 (21.8) | 23 (12.7) | 46 (25.4) | 3 (30.0) | 30 (31.3) | 117/434 (27.0) | 2 (16.7) | 115/422 (27.3) |
| Hypercholesterolaemia b | 312/463 (67.4) | 62 (34.3) | 162/177 (91.5) | 6 (60.0) | 82/95 (86.3) | 323/426 (75.8) | 6 (50.0) | 317/414 (76.6) |
| PAD | 43/466 (9.2) | 7 (3.9) | 20/179 (11.2) | 2 (20.0) | 14 (14.6) | 64/431 (14.8) | 0 | 64/420 (15.2) |
| Stroke (ischaemic or haemorrhagic) | 28/463 (6.0) | 5/179 (2.8) | 15/179 (8.4) | 0 | 8 (8.3) | 16/425 (3.8) | 0 | 16/413 (3.9) |
| Type of ACS | ||||||||
| ST elevation/LBBB MI | 237 (50.6) | 118 (65.2) | 77 (42.5) | 3 (30.0) | 39 (40.6) | – | – | – |
| Non-ST elevation MI | 191 (40.8) | 59 (32.6) | 81 (44.8) | 6 (60.0) | 45 (46.9) | – | – | – |
| Unstable angina | 40 (8.5) | 4 (2.2) | 23 (12.7) | 1 (10.0) | 12 (12.5) | – | – | – |
| Risk factors for CHD | ||||||||
| Current smoker | 131 (28.0) | 73 (40.3) | 36 (19.9) | 4 (40.0) | 18 (18.8) | 33 (7.6) | 1 (8.3) | 32 (7.5) |
| Family history of premature CVD c | 146/418 (34.9) | 52/171 (30.4) | 59/156 (37.8) | 3/8 (37.5) | 32/83 (38.6) | 129/338 (38.2) | 3/10 (30.0) | 126/328 (38.4) |
| Sedentary lifestyle d | 139/322 (43.2) | 58/134 (43.3) | 52/115 (45.2) | 4/7 (57.1) | 25/66 (37.9) | 178/428 (41.6) | 3 (25.0) | 175/416 (42.1) |
| Metabolic syndrome (NCEP-ATP III) | 56/122 (45.9) | 27/63 (42.9) | 18/40 (45.0) | 0 | 11/17 (64.7) | 55/217 (25.3) | 2/7 (28.6) | 53/210 (25.2) |
| Hypertension e | 395 (84.4) | 127 (70.2) | 169 (93.4) | 8 (80.0) | 91 (94.8) | 428 (98.2) | 10 (83.3) | 418 (98.6) |
| Central obesity f | 113/135 (83.7) | 54/69 (78.3) | 38/42 (90.5) | 2/2 (100) | 19/22 (86.4) | 207/290 (71.4) | 5 (41.7) | 202/278 (72.7) |
| BMI > 30 kg/m 2 | 115 (24.6) | 38 (21.0) | 46 (25.4) | 2 (20.0) | 29 (30.2) | 88 (20.2) | 2 (16.7) | 86 (20.3) |
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