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Archives of cardiovascular diseases
Volume 103, n° 8-9
pages 437-446 (août 2010)
Doi : 10.1016/j.acvd.2010.07.001
Received : 8 October 2009 ;  accepted : 23 July 2010
Observational study of adherence to European clinical practice guidelines for the management of acute coronary syndrome in revascularized versus non-revascularized patients – the CONNECT Study
Étude observationnelle d’adhérence aux recommandations européennes dans la prise en charge des syndromes coronaires aigus, revascularisés ou non : l’étude CONNECT
 

Pierre Sabouret a, Philippe Asseman b, Jean Dallongeville c, Jean-Jacques Dujardin d, François Philippe e, Marie-Annick Herrmann f, Gilles Montalescot a,

on behalf of the CONNECT study investigators

a Groupe hospitalier Pitié-Salpétrière, institut de cardiologie, 47-83, boulevard de l’Hôpital, 75651 Paris cedex 13, France 
b Department of Cardiology, Lille University Hospital, Lille, France 
c Pasteur Institute, Lille, France 
d Department of Cardiology, Douai Hospital, Douai, France 
e Department of Cardiology, Institut Mutualiste Montsouris, Paris, France 
f Bristol-Myers Squibb, Rueil-Malmaison, France 

Corresponding author. Fax: +33 01 42 16 29 31.
Summary
Background

The CONNECT study compared clinician adherence to guideline-recommended secondary prevention therapies prescribed at discharge for patients hospitalized for acute coronary syndrome (ACS) in those managed initially with percutaneous coronary intervention (PCI; revascularized) and those who did not undergo revascularization.

Methods

Patients aged greater than or equal to 18 years, hospitalized for a documented ST-segment elevation or non-ST-segment elevation ACS, were enrolled consecutively over 1 month at 238 sites in France.

Results

Compared with revascularized patients (n= 870), non-revascularized patients (n= 706) were significantly older, and a greater proportion were women, had high-blood pressure, type-2 diabetes or a history of atherothrombotic or cardiac disease, but a smaller proportion had a history of coronary angioplasty. On discharge, non-revascularized patients were prescribed beta-blockers, aspirin, statins, angiotensin-converting enzyme inhibitors or adenosine diphosphate receptor antagonists less frequently than revascularized patients. An adherence score greater than or equal to 80% (at least four of the five recommended agents prescribed at discharge) was found in 96.7% of revascularized patients and 74.4% of non-revascularized patients (P <0.001).

Conclusions

Despite a similar or even higher level of cardiovascular risk, non-revascularized ACS patients were prescribed guideline-recommended secondary prevention therapy less frequently than revascularized patients.

The full text of this article is available in PDF format.
Résumé
Objectifs

L’étude CONNECT a comparé la prise en charge thérapeutique, à la sortie de l’hôpital au décours d’un syndrome coronaire aigu (SCA), des patients ayant bénéficié d’une revascularisation coronaire percutanée par rapport aux patients non revascularisés, au moyen d’un score d’adhésion aux recommandations européennes.

Méthodes

Les patients âgés d’au moins 18 ans, et présentant un SCA avec ou sans sus-décalage du segment ST, ont été inclus, de façon consécutive, sur une période d’un mois par 238 centres investigateurs français.

Résultats

Comparés aux patients revascularisés (n =870), les patients non revascularisés étaient significativement plus âgés, plus fréquemment des femmes, et présentaient plus souvent des antécédents d’hypertension artérielle, de diabète de type 2, d’insuffisance cardiaque, d’insuffisance rénale, avec une moindre fréquence d’antécédents d’angioplastie coronaire. À la sortie de l’hôpital, les patients non revascularisés bénéficiaient moins souvent d’un traitement par bêtabloquants, aspirine, statines, inhibiteurs de l’enzyme de conversion (IEC), antagonistes des récepteurs à l’ADP par rapport aux patients revascularisés. Un score d’adhésion aux traitements BASIC supérieur ou égal à 80 % (au moins quatre traitements recommandés présents sur l’ordonnance de sortie) était observé chez 96,7 % de patients revascularisés et chez 70,4 % de patients non revascularisés (p <0,001).

Conclusion

Alors même que leur niveau de risque était au moins équivalent sinon supérieur, les patients présentant un SCA et non revascularisés recevaient moins souvent à la sortie de l’hospitalisation les traitements validés par rapport aux patients revascularisés.

The full text of this article is available in PDF format.

Keywords : Acute coronary syndrome, Adherence, Coronary angioplasty, Clinical practice guidelines, Revascularization

Mots clés : Syndromes coronaires aigus, Angioplastie coronaire, Revascularisation


Introduction

Coronary disease remains the principal cause of death in the Western world, with acute coronary syndrome (ACS) contributing greatly to cardiovascular morbidity and mortality. The constant advances in the treatments available have made effective therapeutic management of ACS extremely complex [1]. Recently, international clinical practice guidelines were published to define the optimum therapeutic strategies for the management of ACS by cardiologists [2, 3, 4, 5, 6]. It is important for these guidelines to be implemented by cardiologists when treating patients with ACS because adherence to guidelines is associated with a better patient prognosis, not only in the acute phase of the syndrome but also in the long-term for secondary prevention [7, 8, 9, 10].

The intervention-based strategy plays a major role in the management of acute-phase patients because of the cardiovascular benefits demonstrated in numerous randomized trials [11]. International guidelines, European as well as North American, therefore advocate early coronary angiography in anticipation of revascularization [3, 4, 5, 6]. In France, this approach is facilitated by the often easy and rapid access to a department of interventional cardiology.

Several recent studies have found that the interventional management of patients hospitalized for ACS would appear to be followed by better secondary prevention management than that of non-revascularized patients [9, 12, 13]. We designed and conducted the CONNECT study (“observational study of the adherence to international guidelines in the management of acute coronary syndrome patients both during hospitalization and at discharge, in revascularized as compared with non-revascularized patients”) to determine whether the same differences in patient management exist in hospitals in France, both for secondary prevention and during the acute phase, and the possible reasons for less than optimal management of patients who do not receive revascularization. The ultimate purpose of examining current management of ACS in France is to stimulate efforts to improve patient care.

Methods

The CONNECT study is a prospective, cross-sectional, observational, multicentre survey conducted in metropolitan France.

Hospital-based cardiologists in public or private cardiology units treating patients with acute-phase ACS were invited to participate in the survey. Patient management was entirely at the discretion of the treating physicians. Patient informed consent was not required. The study protocol was reviewed by the National Council of the Order of Physicians and was performed in accordance with French regulatory requirements, the Declaration of Helsinki and the principles of Good Epidemiologic Practice.

Patients

Male and female patients aged greater than or equal to 18 years who were hospitalized for ST-segment elevation ACS (Q-wave myocardial infarction [MI], STEMI) or non-ST-segment elevation ACS (non-Q-wave MI [non-ST-segment elevation myocardial infarction, NSTEMI]) and unstable angina, and who had not undergone coronary artery bypass graft (CABG) surgery for the present episode and who were not currently participating in a therapeutic trial of a medicinal product were enrolled in the study at the time of their discharge from hospital. Participating physicians recruited the first four consecutive patients who met the selection and revascularization criteria and the first four consecutive patients who met selection and non-revascularization criteria over the period of 1 month at each study center. Study investigators used the standard revascularization and non-revascularization criteria of their cardiology unit. Revascularization was by percutaneous coronary intervention (PCI), which was defined as coronary angioplasty with or without stenting. Patients in either group could receive fibrinolytic treatment; non-revascularized patients were not excluded if they received pharmacological reperfusion therapy with fibrinolytics.

Data collection

Physicians completed a standardized case report form to collect information on patient clinical characteristics, cardiovascular risk factors, medical history, clinical examination, laboratory test results, details of the intervention-based strategy, the treatments prescribed during the acute phase (hospitalization), treatments and reasons for non-prescription at discharge (for treatments for secondary prevention). Reasons were selected from the following list: absence of indication; contraindication; replaced by another therapeutic class; poor tolerability; deemed to have an inadequate benefit-to-risk ratio; refused by patient; and other.

Study endpoints

The main objective was to compare the therapeutic management at discharge of patients who had presented with ACS who underwent revascularization with those who received conservative treatment without revascularization, both overall and according to the type of ACS (with or without ST-segment elevation) by comparing the proportion of patients with a ‘good’ adherence score. Adherence scores were calculated by assigning one point for prescription of any of each of the following treatments as recommended for secondary prevention in the European Society of Cardiology guidelines on the management of ST-segment elevation myocardial infarction (STEMI) and non-ST-segment elevation ACS (NSTE ACS): beta-blockers, aspirin, 3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitors (statins), and angiotensin-converting enzyme (ACE) inhibitors or adenosine diphosphate (ADP) receptor antagonists [14, 15]. One point was assigned when a treatment was not prescribed because of the presence of a contraindication to that treatment because this was considered to be adherence, and thus reducing bias in the interpretation of guideline adherence. The score for each patient was expressed as a percentage of the maximum possible score (five points). Good adherence was defined as an adherence score of greater than or equal to 80% (at least four of the five recommended treatments).

The secondary objectives included the following: a comparison between revascularized and non-revascularized patients (and according to the type of ACS) for clinician adherence to recommendations for patient management at discharge and patient management in the acute phase; an analysis of the predictors of clinician non-adherence; and an analysis of the reasons for lack of prescription of secondary prevention therapies on discharge. An exploratory analysis comparing the risk of death and ischaemic events in the NSTE ACS group (using the thrombolysis in myocardial infarction [TIMI] risk score [16]) between revascularized and non-revascularized patients was also conducted.

Statistical methods

Data from all patients enrolled in the study (the study population) were analyzed descriptively as follows: the sample size, mean and standard deviation±SD, median and range from first to third quartile were calculated for continuous variables, and the number and percentage in relation to the total number of patients was calculated for qualitative variables. Patients in the non-revascularized group who had a normal coronary angiography result were excluded from the statistical analysis in order to avoid bias in interpretation of adherence to secondary prevention treatment.

The search for predictors of non-adherence was carried out using a multivariable logistic regression analysis incorporating variables such as characteristics of the evaluable patients. The statistical analyses were carried out using SAS software V8 (SAS Institute Inc, Cary, NC).

Results

A total of 1735 patients were recruited at 238 sites between September 2006 and June 2007, of whom 23 did not meet selection criteria. Thus, 1712 patients were included in the study population, of whom 870 patients were revascularized and 842 were not revascularized. In the latter group, 60% had a diagnostic coronary angiography of whom most had coronary lesions, but 136 had a normal result and were excluded from the evaluable patient population. Thus results are reported for 1576 patients.

Patients

Patient demographic and clinical characteristics are presented in Table 1, Table 2. The mean age was 67.5±14.7 years and there was a predominance of men (69.8% of patients). The proportion of overweight (body mass index [BMI]25kg/m2 but<30kg/m2) or obese (BMI30kg/m2) patients was 43.3% and 18.6%, respectively. A family history of early onset coronary disease, smoking, dyslipidaemia, hypertension or diabetes mellitus was observed frequently in this cohort (20.9–59.2%). Of the 1576 patients, 553 had Q-wave MI (35.1%) and 1023 had NSTE ACS (64.9%). Of the latter, 528 had non-Q-wave MI and 495 had unstable angina.

The non-revascularized patients were significantly older (P <0.001), had a greater proportion of women (P <0.001), and more often had a history of hypertension (P <0.001), diabetes mellitus (P =0.003) or heart failure (P <0.001) compared with revascularized patients (Table 1, Table 2; see Tables for other significant between-group differences). The risk of death and ischaemic events in patients with NSTE ACS was higher in non-revascularized than revascularized patients (Table 3). A TIMI score greater than or equal to 4 was observed in a greater proportion of non-revascularized patients (43.6% vs. 32.7%; statistical between-group comparison not conducted). In addition, systemic atherothrombotic disease with symptomatic polyarterial lesions, which was defined as patients with a cerebrovascular accident and/or peripheral arterial disease of the lower limbs, was observed more commonly in the non-revascularized group (both P <0.001 vs. revascularized group) (Table 2).

Secondary prevention guideline adherence

The proportion of patients in the evaluable patient population with a ‘good’ adherence score (≥80%) at discharge was 96.7% in the revascularized group and 74.4% in the non-revascularized group (P <0.001), with a greater probability of adherence in the revascularized than non-revascularized group (odds ratio [OR]: 10.0; 95% confidence intervals [CI]: 6.7–15.0). Of the patients with STEMI, the proportion with a good adherence score was even higher than in the overall group, both in revascularized (99.1%) and non-revascularized (76.1%) patients and between-group differences were significant (P <0.001). Conversely, of the patients without ST-segment elevation, this proportion was smaller than in the overall group, and was 95.3% in the revascularized group versus 73.8% in the non-revascularized group (P <0.001). Additionally, prescription at discharge of dual-antiplatelet therapy of aspirin plus ADP receptor antagonists occurred more commonly in the patients who were revascularized compared with those who were not revascularized (98.5% vs. 56.9%; P <0.001).

When analyzed by adherence score (secondary objective), there were more non-revascularized patients with poor adherence than revascularized patients in the study population (Figure 1). In fact, non-revascularized patients received aspirin, beta-blockers, statins, ACE inhibitors or ADP receptor antagonists significantly (P <0.01) less often than revascularized patients (Figure 2; data are shown as absence of prescription in the study population).



Figure 1


Figure 1. 

Comparison of the guideline-adherence scores at discharge for secondary prevention in revascularized and non-revascularized patients with acute coronary syndromes.

Zoom



Figure 2


Figure 2. 

Comparison of the proportion of revascularized and non-revascularized patients admitted for acute coronary syndrome for whom guideline-recommended secondary prevention treatment was not prescribed at discharge. ACE=angiotensin-converting enzyme; ADP=adenosine diphosphate. *P <0.01 vs. revascularized group.

Zoom

Reasons for non-prescription of secondary prevention treatment in non-revascularized patients

The most common reasons for lack of prescription of beta-blockers in non-revascularized patients were the presence of contraindications and substitution with another class of treatment (50.0% and 15.4%, respectively). The proportion of patients not prescribed an ACE inhibitor because of substitution with another class of treatment was 24.5% in the non-revascularized group, and because of an absence of indication was 19.0% in the non-revascularized group and 21.0% in the revascularized group. In both groups, contraindication to ACE inhibitor treatment was rarely given as a reason for non-prescription. ADP receptor antagonists were not prescribed in non-revascularized patients because of an absence of indication (32.3% of cases of non-prescription) and a poor benefit-to-risk ratio (25.7% of cases), whereas, the presence of a contraindication accounted for only 15.7% of cases of non-prescription in this group. This latter reason was, however, the most commonly cited reason for non-prescription of aspirin in non-revascularized patients (35.1% of cases). The benefit-to-risk ratio of statin treatment was considered insufficient in just over one-third of cases of non-prescription of this class of treatment in the non-revascularized group (32.3%), followed by absence of indication (21.5%).

Predictors of secondary prevention guideline non-adherence

Factors predictive of guideline non-adherence at discharge (defined as adherence score of<80%) in the evaluable patient population were unstable angina or NSTEMI, atrial fibrillation, age greater than 80 years, the presence of life-threatening comorbidities, and a normal troponin level (Table 4). Conversely, previous revascularization, the presence of dyslipidaemia and more than two episodes of angina in the 24hours preceding hospitalization were predictive of good adherence.

Acute-phase guideline adherence

The same trends in guideline adherence were observed in acute-phase management, with non-revascularized patients receiving recommended treatments less often than revascularized patients. Fewer patients in the non-revascularized group had a ‘good’ adherence score (≥80%) for acute-phase treatment compared with the revascularized group (72.6% vs. 92.0% of patients). Notably, ADP receptor antagonists were prescribed less frequently at admission for patients who did not undergo revascularization than in those who were revascularized (51.0% vs. 72.4% of patients; P <0.001).

Discussion

The CONNECT study has demonstrated the inadequacy of the therapeutic management of non-revascularized patients, regardless of the type of ACS that prompted their initial hospitalization. This happens despite the fact that non-revascularized patients presented more frequently than revascularized patients with a history of cardiovascular disease and comorbidities. Our analysis showed that beta-blockers, ADP receptor antagonists and ACE inhibitors, in particular, were under-prescribed at discharge in non-revascularized patients (by 18–43%; see Figure 2).

Our findings support those of previous French (OPERA [17]), European regional (Euro Heart [18], EUROASPIRE II [19]), US [20] and multinational (GRACE [9]) registry studies that have highlighted the under-use of recommended pharmacological secondary prevention treatments in patients with atherothrombotic or coronary heart disease [19, 21] or ACS [9, 17, 18, 20]. This under-use is particularly notable for antiplatelet agents [9]. Despite the fact that more recent follow-up registry studies have reported better use of pharmacological treatments in the management of ACS [22, 23, 24], our results suggest that there is still room for improvement in France.

The under-use of beta-blockers in our study (i.e., lack of prescription in 18% of cases) was due to the presence of contraindications or a substitution with another treatment class. Contraindication was also one of the main reasons for lack of prescription of this class of drug in a recently published French survey on the use of evidence-based therapies in patients with NSTE ACS [25]. Our results suggest that, in the absence of contraindications, prescription of beta-blockers is good overall.

Most of our patients received antiplatelet therapy at discharge with aspirin, supporting the findings of two French studies [17, 25] and the GRACE registry (aspirin given in 87% of patients [9]). Yet, the under-prescription at discharge of antiplatelet therapy with ADP receptor antagonists (by 43%) in our non-revascularized patient population is a cause for concern. The Euro Heart II survey [23], REACH [21] and GRACE [9] studies also reported less than optimal prescription of ADP receptor antagonists for secondary prevention. For example, 71% did not receive an ADP receptor antagonist (thienopyridine) in the GRACE registry study [9], with this figure as low as 24% in Europe and 39% in the US [9]. The physicians in our study cited absence of indication and an inadequate benefit-to-risk ratio as the principal reasons for a lack of prescription of ADP receptor antagonists at discharge in non-revascularized patients. Similarly, a lack of indication for treatment was the main reason given by physicians participating in the Euro Heart II survey of patients with ACS for non-prescription of thienopyridines [23]. Yet, the CURE (Clopidogrel in Unstable angina to prevent Recurrent Events) study showed clear improvement in prognosis in patients receiving clopidogrel in addition to standard therapy (as discussed next) [26].

Indeed, dual-antiplatelet therapy was prescribed more frequently in revascularized patients in our study, and by implication, in patients who received a stent. In the GRACE study, treatment with ADP receptor antagonists (usually in combination with aspirin) was significantly more common amongst revascularized patients [9], and a similar trend was noted in a French survey [25]. This suggests clinicians have the perception that antiplatelet dual therapy is appropriate only for revascularized patients, particularly those receiving a stent. Whereas in the CURE study [26, 27, 28] (where 21% of patients were revascularized [27]), benefits of antiplatelet dual therapy were consistent across different patient subgroups, that is, regardless of whether patients were revascularized or not [26], and by implication, whether they had received a stent or not. The problem then is clinician’s knowledge of clinical practice guidelines and the evidence from large clinical trials on which the guideline recommendations are based, including the CURE study. Antiplatelet dual therapy with aspirin plus clopidogrel reduced the risk of major cardiovascular events (composite endpoint of death from cardiovascular causes, non-fatal MI or stroke) over a mean follow-up of 1 year in patients with NSTE ACS [26]. Current guidelines therefore recommend long-term dual-antiplatelet therapy with aspirin and clopidogrel (the latter for 12 months) as secondary prevention treatment, provided neither agent is contraindicated, in ACS patients [4, 6].

Under-prescription of secondary prevention with an ACE inhibitor in non-revascularized patients was not attributable to the presence of contraindications (this was cited rarely as a reason for lack of prescription), rather replacement by another therapeutic class was the main reason, cited in 24.5% of cases of non-prescription in our study. It seems that clinicians in our study were not aware of the full potential use of ACE inhibitors as described in clinical practice guidelines or that they are unconvinced of the benefit in high-risk patients [4, 6]. In the absence of contraindications, the under-prescription of ACE inhibitors may place patients with coronary disease at greater risk of a cardiovascular event.

Finally, guideline adherence for the prescription of statins at discharge was relatively good in non-revascularized and revascularized patients and was in line with that reported in other French studies [17, 25]. Statins are considered standard in the secondary prevention armamentarium, and are associated with a 21% reduction in the incidence of major cardiovascular events when they reduce serum low-density lipoprotein levels by 1mM [29]. Clinicians have readily adopted guideline recommendations to use statins, as described in the EUROASPIRE surveys where there was a significant (P <0.0001) increase of 68% in the use of statins between the first and third surveys (spanning 12 years) [22].

In multivariable analyses, clinician adherence was predicted by the previous coronary angioplasty event, the presence of dyslipidaemia and two episodes or more of angina in the 24hours preceding hospitalization. We hypothesize that these situations are where cardiologists are more likely to pay greater attention to patient management, and in the case of dyslipidaemia would be more likely to prescribe statins. Our results are supported by the CRUSADE study, which showed that invasive management of patients with NSTE ACS was associated with improved guideline adherence both at discharge and in the acute phase [12]. Among the predictors of non-adherence, lack of use of appropriate therapies in the very elderly or those with life-threatening comorbidities may be attributable to a fear of applying guidelines to these high-risk patients.

Adherence to treatment guidelines for the acute phase mirrored that of the secondary prevention setting overall, suggesting that if a treatment is not prescribed in the acute phase, it is not prescribed at discharge either. In particular, ADP receptor antagonists were under-utilized in non-revascularized patients in this setting in our study, being prescribed in only 51.0% of patients, which is a value broadly similar to that observed in other studies (52–58% of patients in OPERA [17], CRUSADE [24] and GRACE [30]). Indeed, a recent analysis of CRUSADE data by Alexander et al. supports our conclusion that non-revascularized patients are undertreated; about 50% of patients with NSTE ACS who did not undergo PCI (within 24hours) did not receive guideline-recommended therapy with clopidogrel [31]. As a result, patient outcomes are adversely affected; clopidogrel given in the acute phase (i.e., within 24hours of hospitalization) was associated with lower risk of in-hospital mortality than non-use of clopidogrel (OR: 0.68; 95% CI: 0.61–0.77) [31].

All of the available data in the literature, including registry data, stress the need to optimize the prescribing of acute-phase and secondary prevention treatments for ACS patients in order to improve concordance between evidence-based medicine and current practice, and as a result, patient outcomes.

To reduce the potential for bias in our analysis of secondary prevention management, we excluded 136 patients with a normal coronary angiography from the non-revascularized group (16.1%). Moreover, the observed under-use of recommended pharmacological treatments in the management of ACS in our study cannot be explained by the presence of contraindications to treatment because the adherence score was weighted to account for contraindications.

One can argue that in the group of patients with unstable angina and no coronary angiography, the absence of proof of coronary disease may explain the difference in the non-adherence factors. An analysis was performed comparing non-revascularized patients with an abnormal coronary angiography versus those who did not undergo coronary angiography. Among the patients with no coronary angiography in the non-revascularized group, 31.4% had unstable angina, whereas 38.1% of patients with coronary angiography had unstable angina. This difference was not statistically significant (P =0.1). In the group with unstable angina and no coronary angiography, significantly more patients have a history of CABG, cardiac insufficiency and comorbidities compared with patients in the group with coronary angiography. Similar differences were observed between both groups (with or without coronary angiography for patients with Q-wave and non Q-wave MI [data not shown]). These data are concordant with the major reasons given for no coronary angiography, which were age, comorbidity and renal insufficiency. Therefore, the coronary status by itself (no proof of coronary disease) does not explain the differences in the non-adherence factors.

Any potential bias in the recruitment of cardiologists such as can exist in this type of study, which is based on voluntary participation by doctors, was eliminated by comparing the general characteristics of the investigating cardiologists with those of a general population of French cardiologists, for whom data was obtained from the DREES (French Directorate for Research, Studies, Evaluation and Statistics) at the time the study was set up. No physicians were excluded from participating in this study on the basis of this analysis. In addition, any potential bias in the selection of patients was avoided by enrolling the first four consecutive patients who met the selection and revascularization criteria and the first four who met selection and non-revascularization criteria. The conduct of the study might have led more to an overestimation rather than underestimation of the level of guideline adherence as compared with usual clinical practice.

Conclusion

Patients with ACS who do not undergo revascularization by PCI during their initial hospitalization receive guideline-recommended secondary prevention treatment at discharge less often than revascularized patients, even though their cardiovascular risk level is at least equivalent to or greater than that of revascularized patients. Patient characteristics such as age, the presence of comorbidities, atrial fibrillation, history of unstable angina or NSTEMI are predictive of clinician non-adherence to clinical guidelines as illustrated by under-prescribing of recommended treatments, leading to a paradoxical under-treatment of high-risk patients. Progress is therefore essential for the optimization of treatment of non-revascularized ACS patients and thus to improve their cardiovascular prognosis in the short and medium term.

Conflict of interest statement

P. Sabouret discloses the following relationships: consulting or lecture fees from Bristol-Myers Squibb, MSD, Pfizer, Sanofi-Aventis, Schering-Plough; P. Asseman declares no conflict of interest; J. Dallongeville declares potential conflicts of being a member of the CONNECT study scientific board and a scientific advisor on the ‘Institut d’athérotrhombose’ (France); J.J. Dujardin declares receipt of consulting fees from Sanofi-aventis and Bristol-Myers Squibb; F. Phillipe reports receiving lecture fees from Sanofi-Aventis, Bristol-Myers Squibb, Astra-Zeneca, and Takeda; and G. Montalescot discloses the following relationships: Research Grants (to the Institution) from Bristol-Myers Squibb, Boston Scientific, Centocor, Cordis, Eli-Lilly, ‘Fédération française de cardiologie’, ‘Fondation de France’, Guerbet Medical, Inserm, Medtronic, Pfizer, Sanofi-Aventis Group, ‘Société française de cardiologie’; consulting or lecture fees from Astra-Zeneca, Bayer, Boehringer-Ingelheim, Bristol-Myers Squibb, Daichi-Sankyo, Eisai, Eli-Lilly, Menarini, MSD, Novartis, Portola, Sanofi-Aventis Group, Schering-Plough and The Medicines Company.


Acknowledgements

We would like to thank all cardiologists who participated in the study, and acknowledge the expert assistance of Marie-Helene Barlet of Altigapharma for co-ordinating the study and Anne Fillipovics of Bristol-Myers Squibb for her contribution to the statistical analysis of the study data. We thank Tracy Harrison of Wolters Kluwer Health for providing medical writing assistance, which was funded by Sanofi-aventis and Bristol-Myers Squibb, France.

Funding/Support : The CONNECT study was supported by an unrestricted grant from Sanofi-aventis and Bristol-Myers Squibb, France.

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