Clinical characteristics and outcomes of COMPASS eligible patients in France. An analysis from the REACH Registry.

BACKGROUND: Following the publication of the COMPASS trial, the European Medicines Agency has approved a regimen of combination of rivaroxaban 2.5mg twice daily and a daily dose of 75-100mg acetylsalicylic acid (ASA) for patients with coronary artery disease (CAD) or symptomatic peripheral artery disease (PAD) at high risk of ischemic events. However, the applicability of such a therapeutic strategy in France is currently unknown. AIMS: To describe the proportion of patients eligible to COMPASS in France, their baseline clinical characteristics and the rate of major adverse cardiovascular events, using the REACH registry. METHODS: From the the REduction of Atherothrombosis for Continued Health (REACH) registry database, a large international registry of patients with, or at risk, of atherothrombosis, we analyzed patients included in France with either established CAD and/or PAD and fulfilling the inclusion and exclusion criteria of the COMPASS trial. The ischemic outcome was a composite of cardiovascular (CV) death, myocardial infarction (MI), or stroke, and serious bleeding were defined as haemorrhagic stroke or bleeding leading to hospitalization or transfusion. RESULTS: Among more than 65000 patients enrolled in REACH, 2.012 patients were evaluable and enrolled in France. Among them, 1194 patients (59.3%) were eligible to COMPASS. The main reasons for exclusion of the COMPASS trial, were high bleeding risk (59.1%), anticoagulant use (43.4%), requirement for dual antiplatelet therapy within 1 year of an ACS or PCI (24.7%). In the "COMPASS eligible population", the rate of MACE (CV, MI and stroke) at 4 years follow-up was 13.4% [11.3-15.8], and serious bleeding was 2.5% at 4 years [1.6-3.4]. Patients with polyvascular disease (n=219) had the highest rate of MACE, compared with patients with CAD only and PAD only (19.1% [13.9-26.1] vs. 11.6% [9.1-14.8] vs 13.2% [9.2-18.8], P<0.0001, respectively). CONCLUSION: The COMPASS therapeutic strategy in France appears to be applicable to more than half of CAD or PAD patients. This population appears at high residual risk of atherothrombotic events, and patients with polyvascular disease experienced the highest rate of events.

Blood transfusion and ischaemic outcomes according to anemia and bleeding in patients with non-ST-segment elevation acute coronary syndromes: Insights from the TAO randomized clinical trial.

BACKGROUND: The benefits and risks of blood transfusion in patients with acute myocardial infarction who are anemic or who experience bleeding are debated. We sought to study the association between blood transfusion and ischemic outcomes according to haemoglobin nadir and bleeding status in patients with NST-elevation myocardial infarction (NSTEMI). METHODS: The TAO trial randomized patients with NSTEMI and coronary angiogram scheduled within 72h to heparin plus eptifibatide versus otamixaban. After exclusion of patients who underwent coronary artery bypass surgery, patients were categorized according to transfusion status considering transfusion as a time-varying covariate. The primary ischemic outcome was the composite of all-cause death or MI within 180 days of randomization. Subgroup analyses were performed according to pre-transfusion hemoglobin nadir and bleeding status. RESULTS: 12,547 patients were enrolled. Among these, blood transfusion was used in 489 (3.9%) patients. Patients who received transfusion had a higher rate of death or MI (29.9% vs. 8.1%, p<0.01). This excess risk persisted after adjustment on GRACE score and nadir of hemoglobin (HR 3.36 95%CI 2.63-4.29 p<0.01). Subgroup analyses showed that blood transfusion was associated with a higher risk in patients without overt bleeding (adjusted HR 6.25 vs. 2.85; p-interaction 0.001) as well as in those with hemoglobin nadir > 9.0 g/dl (HR 4.01; p-interaction<0.0001). CONCLUSION: In patients with NSTEMI, blood transfusion was associated with an overall increased risk of ischaemic events. However, this was mainly driven by patients without overt bleeding and those hemoglobin nadir > 9.0g/dl. This suggests possible harm of transfusion in those groups.

[Elderly patients with coronary artery disease are at high bleeding risk]. / Le coronarien âgé : un patient à haut risque hémorragique.

Bleeding complications are frequent in coronary artery disease patients and are associated with increased mortality. Among clinical factors increasing the risk of bleeding, age appears to be a major determinant, whatever the clinical presentation (stable disease, acute coronary syndrome, PCI). Evidence of the role of age comes from the weight given to age in most existing bleedingrisk scores.

Geographic differences in outcomes in outpatients with established atherothrombotic disease: results from the REACH Registry.

AIMS: There are major differences in the prevalence and management of patients with atherothrombotic disease including coronary artery disease (CAD), cerebrovascular disease (CVD) and peripheral artery disease (PAD) across different geographical regions. There is, however, little data allowing comparisons of management and outcomes across broad geographic regions. We aimed to describe geographical differences in baseline characteristics, management and outcomes in stable outpatients with established atherothrombotic disease. METHODS AND RESULTS: From the REACH Registry of atherothrombosis, patients with documented CAD, PAD or CVD and with 4-year follow-up were included. Baseline characteristics, treatments and 4-year outcomes were recorded. Event rates were compared between geographical regions and were adjusted for risk scores predicting ischemic and bleeding events. The analyses of baseline characteristics and medications according to geographical region showed marked differences. For the composite primary outcome (cardiovascular death, non-fatal myocardial infarction (MI) and non-fatal stroke), rates ranged from 12.1% in Japan to 18.2% in Eastern Europe. After adjustment, substantial variations remained: taking North America as a reference, patients from Western Europe and Japan had a lower risk of primary outcome event (hazard ratio (HR) 0.93; p = 0.045, and HR = 0.67; p < 0.001 respectively) whereas patients from Eastern Europe had a higher risk (HR = 1.24; p < 0.001). There were no obvious differences between patients from North America and those from Latin America, the Middle East and Asia. CONCLUSION: There are important variations in the outcomes of patients with atherothrombotic across geographic regions. These observations have important implications for public health and clinical research.

[Comparison between European Society of Cardiology (ESC) and American College of Cardiology/American Heart Association (ACC/AHA) guidelines for initial management of ST-elevation myocardial infarction (STEMI)]. / Comparaison des recommandations européennes (ESC) et américaines (ACC/AHA) concernant la prise en charge initiale des syndromes coronariens aigus avec sus décalage du segment ST.

The European Society of Cardiology (ESC) and American College of Cardiology/American Heart Association (ACC/AHA) have recently updated guidelines for management of ST-elevation myocardial infarction (STEMI). The aim of this study is to compare the both recommendations.

Consensus statement on the care of the hyperglycaemic/diabetic patient during and in the immediate follow-up of acute coronary syndrome.

The Diabetes and Cardiovascular Disease study group of the Société francophone du diabète (SFD, French Society of Diabetes) in collaboration with the Société française de cardiologie (SFC, French Society of Cardiology) have devised a consensus statement on the care of the hyperglycaemic/diabetic patient during and in the immediate follow-up of acute coronary syndrome (ACS); in particular, it includes the different phases of ACS [the intensive care unit (ICU) period, the post-ICU period and the short-term follow-up period after discharge, including cardiac rehabilitation] and also embraces all of the various diagnostic and therapeutic issues with a view to optimizing the collaboration between cardiologists and diabetologists. As regards diagnosis, subjects with HbA(1c) greater or equal to 6.5% on admission may be considered diabetic while, in those with no known diabetes and HbA(1c) less than 6.5%, it is recommended that an OGTT be performed 7 to 28 days after ACS. During hospitalization in the ICU, continuous insulin treatment should be initiated in all patients when admission blood glucose levels are greater or equal to 180 mg/dL (10.0 mmol/L) and, in those with previously known diabetes, when preprandial glucose levels are greater or equal to 140 mg/dL (7.77 mmol/L) during follow-up. The recommended blood glucose target is 140-180 mg/dL (7.7-10 mmol/L) for most patients. Following the ICU period, insulin treatment is not mandatory for every patient, and other antidiabetic treatments may be considered, with the choice of optimal treatment depending on the metabolic profile of the patient. Patients should be referred to a diabetologist before discharge from hospital in cases of unknown diabetes diagnosed during ACS hospitalization, of HbA(1c) greater or equal to 8% at the time of admission, or newly introduced insulin therapy or severe/repeated hypoglycaemia. Referral to a diabetologist after hospital discharge is recommended if diabetes is diagnosed by the OGTT, or during cardiac rehabilitation in cases of uncontrolled diabetes (HbA(1c) ≥ 8%) or severe/repeated hypoglycaemia.

[Risk factors of upper gastrointestinal complications in outpatients on antiplatelet therapy: description and management]. / Facteurs de risque de complications digestives des patients sous antiagrégant plaquettaire suivis en cardiologie de ville : description et prise en charge.

OBJECTIVES: Patients on antiplatelet therapy have a gastrointestinal bleeding risk. It is increased by risk factors. The frequency of those risk factors, the prevalence of upper digestive symptoms and their management in patients on antiplatelet agents is unknown. PATIENTS AND METHODS: We performed an observational multi-centred prospective survey among 560 French cardiologists with private practice. Each cardiologist completed a questionnaire for the first four patients treated with antiplatelet agents in primary or secondary prevention. RESULTS: Among the 2182 patients included, (age = 67 ± 11 years; 74% male), 83% had at least one gastrointestinal bleeding risk factor and 38.9% had a history of upper digestive tract symptom. A history of gastrointestinal bleeding was reported in 3.4% and a history of documented gastro-duodenal ulcer in 5.5%. A proton pump inhibitor was already prescribed in 39% of the patients. At the time of the consultation, upper digestive symptoms were described in 21% of the patients. In those patients with symptoms, 85% had no modification in antiplatelet therapy and 62.7% were prescribed gastro-protective drugs (proton pump inhibitors: 51.8%, H(2)-blockers 3.6% other anti-acid medication: 7.3%). CONCLUSION: Among patients on antiplatelet agents, the prevalence of upper digestive symptoms and risk factors for gastrointestinal bleeding is high. Preventative management needs to be clarified in this population.

Consensus statement on the care of the hyperglycaemic/diabetic patient during and in the immediate follow-up of acute coronary syndrome.

The Diabetes and Cardiovascular Disease study group of the Société francophone du diabète (SFD, French Society of Diabetes) in collaboration with the Société française de cardiologie (SFC, French Society of Cardiology) have devised a consensus statement on the care of the hyperglycaemic/diabetic patient during and in the immediate follow-up of acute coronary syndrome (ACS); in particular, it includes the different phases of ACS [the intensive care unit (ICU) period, the post-ICU period and the short-term follow-up period after discharge, including cardiac rehabilitation] and also embraces all of the various diagnostic and therapeutic issues with a view to optimalizing the collaboration between cardiologists and diabetologists. As regards diagnosis, subjects with HbA(1c) greater or equal to 6.5% on admission may be considered diabetic while, in those with no known diabetes and HbA(1c) less than 6.5%, it is recommended that an OGTT be performed 7 to 28days after ACS. During hospitalization in the ICU, continuous insulin treatment should be initiated in all patients when admission blood glucose levels are greater or equal to 180mg/dL (10.0mmol/L) and, in those with previously known diabetes, when preprandial glucose levels are greater or equal to 140mg/dL (7.77mmol/L) during follow-up. The recommended blood glucose target is 140-180mg/dL (7.7-10mmol/L) for most patients. Following the ICU period, insulin treatment is not mandatory for every patient, and other antidiabetic treatments may be considered, with the choice of optimal treatment depending on the metabolic profile of the patient. Patients should be referred to a diabetologist before discharge from hospital in cases of unknown diabetes diagnosed during ACS hospitalization, of HbA(1c) greater or equal to 8% at the time of admission, or newly introduced insulin therapy or severe/repeated hypoglycaemia. Referral to a diabetologist after hospital discharge is recommended if diabetes is diagnosed by the OGTT, or during cardiac rehabilitation in cases of uncontrolled diabetes (HbA(1c)≥8%) or severe/repeated hypoglycaemia.

[Chloroquine cardiotoxicity in long-term lupus therapy in two patients]. / Cardiotoxicité après un traitement au long cours par chloroquine chez deux patientes lupiques.

BACKGROUND: The antimalarial compounds chloroquine and hydroxychloroquine are widely used in the treatment of connective tissue diseases and are usually well tolerated. We report two cases of chloroquine cardiotoxicity. PATIENTS AND METHODS: Two women (aged 43 and 48 years) were treated for 5 years for lupus. They developed severe conduction disturbances requiring a pacemaker. Plasma chloroquine concentrations were abnormally high in both cases. In one case, a genetic polymorphism modulating the activity of a cytochrome involved in chloroquine metabolism (CYP2C8) was identified. DISCUSSION: Since 1965, 60 cases of occasionally severe cardiotoxicity have been reported following long-term treatment with chloroquine in most cases, but also with hydroxychloroquine. This toxicity must be detected early and close cardiac assessment is required.

Antiplatelet therapy following drug-eluting stent implantation: new clinical data and recommendations.

Technological developments in percutaneous coronary interventions (PCI) allow the possibility for less invasive revascularization in an increasing number of patients with atherosclerotic coronary artery disease. Bare-metal stents (BMS) have considerably improved the efficacy of PCI in addition to greatly reducing restenosis. However, even with standard stents, restenosis has remained a significant limitation of this revascularization technique. The advent of drug-eluting stents (DES) has dramatically reduced in-stent restenosis and, as a result, the need for repeat revascularization. However, their potential thrombogenicity has raised concerns about their clinical utility and long-term safety. Indeed, there is a possible higher rate of late stent thrombosis (LST) with DES compared with BMS. Antiplatelet therapy has been shown to be efficient in preventing DES thrombosis. Nevertheless, in the future, significant improvement will occur to improve the safety and efficacy of this therapy. This article will summarize the pathophysiology and the epidemiology of stent thrombosis (ST). Definitions of definite, probable and possible ST will be described. Furthermore, clinical risk factors for ST will be clearly enumerated. Then, the various antiplatelet therapeutic strategies used to prevent ST will be taken in consideration. Finally, a summary of the major recommendations about antiplatelet therapy made by some of the most prestigious learned societies will be presented.

[Treatment of intrastent restenosis by drug eluting stents: experience from one cardiology centre]. / Traitement des resténoses intrastent par un stent actif: experience monocentrique.

Many interventional treatments have been proposed for intrastent stenosis, in particular by drug-eluting stents, with encouraging results. The aim of this study was to assess the clinical outcome of patients with restenosis of an ordinary uncovered stent treated by a drug eluting stent in a prospective series. The register included 43 patients (50 intrastent restenoses) treated by a drug eluting stent (Cypher or Taxus). The restenosis lesion was focal in 32% of cases with an average length of 14.8 +/- 8 mm and diameter inferior to 2.5 mm in 48% of cases. A Cypher stent was implanted in 44% of cases and a Taxus stent in 56% of cases. After an average follow-up of 6.7 +/- 1.3 months, the major adverse cardiac event rate was 9.3%. It included one transmural infarct in a patient, due to stent thrombosis, and symptomatic restenoses in 3 patients (clinical restenosis rate: 7%). An angiographic control was performed in 15 patients (35%) identifying focal restenosis at the exit of the stent in the 3 symptomatic patients. As in previously reported studies, these results show that with well conducted platelet antiaggregant therapy, the treatment of intrastent restenosis with a drug eluting stent is effective with a low rate of adverse cardiovascular events which compares favourably with previously proposed techniques of management.