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1.
Int J Cardiol ; 330: 259-265, 2021 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-33592237

RESUMEN

BACKGROUND: Friedreich's ataxia (FA) is a rare autosomal recessive mitochondrial disease most commonly due to a triplet repeat expansion guanine-adenine-adenine (GAA) in the FXN gene. Cardiac disease is the major cause of death, patients with reduced left ventricular ejection fraction (LVEF) having the worse prognosis. Longitudinal strain (LS) appeared to be a better predictor of outcome than LVEF in different diseases. We compared the prognostic value of LS measured from the 4 chambers view to LVEF. METHODS: From 2003 to 2017 consecutive patients with FA were included and LS analysis was retrospectively performed. RESULTS: We studied 140 patients, with a median age of 34 (26-41) years (Q1-Q3) with age at onset of 14 (11-19) years and GAA repeats on the shorter allele of 600 (467-783) pb. Mean LS was 19.9 ± 5.0% and LVEF 64 ± 8%. After a mean follow-up of 7.4 ± 3.9 years, 14 patients died. In univariate Cox analysis, all-cause mortality was associated with: LS (HR 0.83; 95%CI, 0.75-0.91, p = 0.0002), LVEF (HR 0.30; 95%CI, 0.19-0.49, p < 0.0001), GAA repeats on the shorter allele (HR 1.29; 95%CI, 1.10-1.51, p = 0.002), age at onset (HR 0.87; 95%CI, 0.77-0.98, p = 0.018), LVSystolic Diameter (HR 1.17; 95%CI, 1.09-1.26, p < 0.0001), LVMass index (HR 1.02; 95%CI, 1.00-1.04, p = 0.027), and LVDiastolic Diameter (HR1.12; 95%CI, 1.01-1.23, p = 0.028). In multivariate analysis, LVEF was the only independent predictor of mortality (HR 0.41; 95%CI, 0.23-0.74, p = 0.0029). CONCLUSION: In FA, LS was not an independent predictor of mortality, LVEF remained the only independent predictor in the present study.


Asunto(s)
Ataxia de Friedreich , Adulto , Ataxia de Friedreich/diagnóstico , Ataxia de Friedreich/genética , Humanos , Pronóstico , Estudios Retrospectivos , Volumen Sistólico , Función Ventricular Izquierda
2.
Int J Cardiol ; 323: 281-284, 2021 01 15.
Artículo en Inglés | MEDLINE | ID: mdl-32918938

RESUMEN

INTRODUCTION: COVID-19 infection is commonly complicated with pro-thrombotic state and endothelial dysfunction. While several studies reported a high incidence of venous thromboembolic events. The occurrence of arterial thromboses are yet rarely described and could be underestimated. OBJECTIVES: To describe the clinical and biological characteristics of COVID-19 patients presenting with an associated arterial thromboembolic event. MATERIAL AND METHODS: We performed a retrospective multicentric study in 3 centers between France and Italy. All patients with a confirmed SARS-CoV-2 infection and arterial thromboembolic events were included in the analysis. RESULTS: From March 8th to April 25th 2020, we identified 20 patients (24 events) with arterial thromboembolic events over 209 admitted patients (9.6%) with severe COVID-19 infection. Arterial thrombotic events included acute coronary occlusions (n = 9), stroke (n = 6), limb ischemia (n = 3), splenic infarcts (n = 3), aortic thrombosis (n = 2) and occlusive mesenteric ischemia (n = 1). At the time of the event, 10/20 (50%) of patients received thromboprohylaxis, 2/20 (10%) were receiving treatment dose anticoagulation and 5/20 (25%) were receiving antiplatelet therapy. CONCLUSION: Our observations suggest that serious arterial thrombotic events might occur in Covid-19 patients. However, the exact incidence of such events and the best way to prevent them yet remains to be investigated.


Asunto(s)
COVID-19/complicaciones , Oclusión Coronaria/virología , Isquemia/virología , Isquemia Mesentérica/virología , Infarto del Bazo/virología , Accidente Cerebrovascular/virología , Trombosis/virología , Anciano , Anticoagulantes/uso terapéutico , Aorta , Extremidades/irrigación sanguínea , Femenino , Francia/epidemiología , Humanos , Italia/epidemiología , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/uso terapéutico , Estudios Retrospectivos , SARS-CoV-2
3.
Ann Cardiol Angeiol (Paris) ; 69(4): 158-166, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32778388

RESUMEN

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.


Asunto(s)
Anticoagulantes/administración & dosificación , Aspirina/administración & dosificación , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Enfermedad Arterial Periférica/tratamiento farmacológico , Inhibidores de Agregación Plaquetaria/administración & dosificación , Rivaroxabán/administración & dosificación , Anciano , Análisis de Varianza , Aterosclerosis , Enfermedad de la Arteria Coronaria/epidemiología , Esquema de Medicación , Femenino , Estudios de Seguimiento , Francia/epidemiología , Hemorragia/etiología , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Infarto del Miocardio/epidemiología , Selección de Paciente , Intervención Coronaria Percutánea , Enfermedad Arterial Periférica/epidemiología , Estudios Prospectivos , Sistema de Registros/estadística & datos numéricos , Factores de Riesgo , Accidente Cerebrovascular/epidemiología , Trombosis/etiología , Factores de Tiempo , Resultado del Tratamiento
4.
Ann Cardiol Angeiol (Paris) ; 66(6): 373-379, 2017 Dec.
Artículo en Francés | MEDLINE | ID: mdl-29096907

RESUMEN

Coronary thrombosis remains the leading cause for cardiovascular death in France. Great advances have been made in the knowledge of the basic mechanism involved in coronary thrombogenesis and in antithrombotic treatments. They have led to substantial survival benefit after myocardial infarction and enabled development of tailored therapeutic strategies, especially for high-risk patients. Direct oral anticoagulants have now entered the game for secondary prevention after coronary thrombosis.


Asunto(s)
Trombosis Coronaria/tratamiento farmacológico , Trombosis Coronaria/fisiopatología , Fibrinolíticos/administración & dosificación , Medicina Integrativa , Calidad de Vida , Administración Oral , Trombosis Coronaria/mortalidad , Humanos , Factores de Riesgo , Resultado del Tratamiento
5.
Clin Pharmacol Ther ; 100(3): 287-94, 2016 09.
Artículo en Inglés | MEDLINE | ID: mdl-27213804

RESUMEN

Interindividual variability in platelet aggregation is common among patients treated with clopidogrel and both high on-treatment platelet reactivity (HTPR) and low on-treatment platelet reactivity (LTPR) increase risks for adverse clinical outcomes. CYP2C19 influences clopidogrel response but only accounts for ∼12% of the variability in platelet reactivity. To identify novel variants implicated in on-treatment platelet reactivity, patients with coronary artery disease (CAD) with extreme pharmacodynamic responses to clopidogrel and wild-type CYP2C19 were subjected to exome sequencing. Candidate variants that clustered in the LTPR subgroup subsequently were genotyped across the discovery cohort (n = 636). Importantly, carriers of B4GALT2 c.909C>T had lower on-treatment P2Y12 reaction units (PRUs; P = 0.0077) and residual platelet aggregation (P = 0.0008) compared with noncarriers, which remained significant after adjusting for CYP2C19 and other clinical variables in both the discovery (P = 0.0298) and replication (n = 160; PRU: P = 0.0001) cohorts. B4GALT2 is a platelet-expressed galactosyltransferase, indicating that B4GALT2 c.909C>T may influence clopidogrel sensitivity through atypical cell-surface glycoprotein processing and platelet adhesion.


Asunto(s)
Plaquetas/efectos de los fármacos , Citocromo P-450 CYP2C19/genética , Galactosiltransferasas/genética , Inhibidores de Agregación Plaquetaria/farmacología , Ticlopidina/análogos & derivados , Adulto , Anciano , Aspirina/administración & dosificación , Clopidogrel , Enfermedad de la Arteria Coronaria/tratamiento farmacológico , Quimioterapia Combinada , Exoma , Femenino , Genotipo , Humanos , Masculino , Persona de Mediana Edad , Fenotipo , Proyectos Piloto , Inhibidores de Agregación Plaquetaria/administración & dosificación , Ticlopidina/administración & dosificación , Ticlopidina/farmacología
6.
Thromb Haemost ; 110(5): 1055-64, 2013 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-23925438

RESUMEN

A new ELISA technique has been developed to measure the vasodilator-associated stimulated phosphoprotein (VASP) platelet reactivity index (PRI) in clopidogrel-treated patients. This technique has not been evaluated in acute coronary syndrome (ACS) patients or in prasugrel-treated patients. We assessed the accuracy of ELISA-VASP to identify high on-treatment platelet reactivity (HPR) in ACS patients in comparison with established platelet function tests. Platelet reactivity was measured in 240 ACS patients treated with clopidogrel (75 or 150 mg) or prasugrel (5 or 10 mg) using flow cytometry (FC-VASP) and the ELISA-VASP technique, light transmission aggregometry (LTA) and VerifyNow-P2Y12 assay (VN-P2Y12). When using the ELISA-VASP PRI, the rate of patients with HPR in the overall ACS population was 15.5%, including a 27% rate in clopidogrel-treated patients and a 4% rate in prasugrel-treated patients. There was a strong correlation between ELISA-VASP PRI and FC-VASP PRI (r = 0.83, r2 = 0.68 p < 0.0001) with an area under the receiver-operating characteristics (ROC) curve to identify HPR (VASP-PRI >50% with FC-VASP) of 0.94, p<0.0001. The threshold of 60% for ELISA-VASP PRI provided the best accuracy (likelihood ratio= 23.67) to identify patients with HPR when compared to FC-VASP, LTA or VN-P2Y12 assays. In conclusion, ELISA-VASP is a fast, easy-to-use and specific test to identify HPR in ACS patients on thienopyridines. A 60% threshold value displays the best accuracy to identify HPR in these patients.


Asunto(s)
Síndrome Coronario Agudo/diagnóstico , Anticoagulantes/administración & dosificación , Moléculas de Adhesión Celular/metabolismo , Ensayo de Inmunoadsorción Enzimática/métodos , Proteínas de Microfilamentos/metabolismo , Fosfoproteínas/metabolismo , Piperazinas/administración & dosificación , Tiofenos/administración & dosificación , Ticlopidina/análogos & derivados , Síndrome Coronario Agudo/sangre , Anciano , Separación Celular , Clopidogrel , Estudios de Factibilidad , Femenino , Citometría de Flujo , Humanos , Masculino , Persona de Mediana Edad , Pruebas de Función Plaquetaria , Clorhidrato de Prasugrel , Estándares de Referencia , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Ticlopidina/administración & dosificación
7.
Int J Cardiol ; 167(6): 2646-52, 2013 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-22795712

RESUMEN

BACKGROUND: To assess the impact of impaired renal function (IRF) and timing of catheterization (immediate versus delayed intervention) on outcomes in intermediate/high risk NSTE-ACS patients. METHODS: We performed a post-hoc analysis of the randomized ABOARD population to compare 1) patients with vs. without IRF and 2) the two intervention strategies in patients with IRF. A creatinine clearance <60 mL/min defined IRF. The primary endpoint was the in-hospital peak troponin I value; the secondary endpoints were a) the composite of death, myocardial infarction, urgent revascularization or recurrent ischemia (death/MI/UR/RI) and b) STEEPLE major bleeding (MB) at 1-month follow-up. RESULTS: Among the 345 patients, 75 (21.7%) had IRF. Patients with IRF were older, had more comorbidities and were at higher cardiovascular risk. Radial catheterization was predominant (84%). Among IRF patients, 37 (49%) and 38 (51%) patients were randomized to an immediate and delayed strategy, respectively. The primary and secondary endpoints rates were not different for the two comparisons. IRF was associated with more death (5.3% vs. 1.1%, p=0.043) and non-CABG MB (9.3% vs. 2.2%, p=0.001). In patients with IRF, a delayed strategy was associated with more recurrent ischemia (28.9% vs. 8.1%, p=0.021). Absence of clopidogrel pretreatment, insulin therapy and left main culprit lesion were independently associated with death/MI/UR/RI, while age and CABG surgery were related with MB. CONCLUSION: IRF is associated with worse outcomes in NSTE-ACS patients. The primary results of the ABOARD study apply also to patients with IRF in which the timing of catheterization does not impact hard outcomes.


Asunto(s)
Síndrome Coronario Agudo/sangre , Síndrome Coronario Agudo/terapia , Cateterismo Cardíaco/métodos , Insuficiencia Renal/sangre , Insuficiencia Renal/terapia , Troponina I/sangre , Síndrome Coronario Agudo/epidemiología , Adulto , Anciano , Angioplastia Coronaria con Balón/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Insuficiencia Renal/epidemiología , Factores de Tiempo , Resultado del Tratamiento
8.
Int J Cardiol ; 167(3): 739-44, 2013 Aug 10.
Artículo en Inglés | MEDLINE | ID: mdl-22459370

RESUMEN

BACKGROUND: Late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) enables the estimation of myocardial infarct (MI) extent. Nevertheless, manual quantification is time consuming and subjective. We sought to assess MI volume with different quantitative methods in both acute (AMI) and chronic MI (CMI). METHODS: CMR was performed 50 ± 21 h after MI in 52 patients and was repeated 100 ± 21 days later in a subgroup of 34 patients. Then, necrosis volumes were quantified using: 1) manual delineation, 2) automated fuzzy c-means method, and 3) +2 to 6 SD thresholding approaches. Results were compared against peak values of serum Troponin I (TnI), creatine kinase (CK) and left ventricular (LV) functional parameters: LV ejection fraction (LVEF), indexed end-diastolic (EDVi), end-systolic volumes (ESVi) and the number of hypokinetic segments (NbHk). RESULTS: For CMI, quantitative evaluation of infarct size using manual, +2SD, +3 SD and fuzzy c-means provided equivalent results in terms of correlation coefficients for comparisons of MI volumes against LV function parameters (LVEF: r>0.79, p<0.0001; ESVi: r>0.82, p<0.0001, EDVi: r>0.67, p<0.0001, NbHk: r>0.54, p<0.0009). For AMI, +2SD and fuzzy c-means approaches provided higher correlations for comparisons of AMI volumes against biochemical markers (CK: r>0.79, p<0.0001,TnI: r>0.77, p<0.0001) and chronic LV function parameters (LVEF: r>0.82, p<0.0001, NbHk: r>0.59, p<0.0002). CONCLUSIONS: The fuzzy c-means and 2SD methods provided highest correlations with biochemical MI quantification as well as LV function parameters. The fuzzy c-means approach which does not require an arbitrary identification of the remote myocardium is fast and reproducible. It may be clinically useful in the evaluation of patients with MI.


Asunto(s)
Imagen por Resonancia Cinemagnética/normas , Infarto del Miocardio/diagnóstico , Estadística como Asunto/normas , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/epidemiología , Estudios Prospectivos
10.
QJM ; 105(10): 935-48, 2012 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-22543683

RESUMEN

Non-ST elevation (NSTE) myocardial infarction and unstable angina are the most common clinical presentations of acute coronary syndrome (ACS). Platelet activation is central to the pathogenesis of NSTE-ACS and consensus guidelines that advocate early revascularization supported by intensive antiplatelet therapy. This review examines the drugs used concurrently with aspirin as dual antiplatelet therapy in the NSTE-ACS setting. Clopidogrel represented an important therapeutic advance. However, variations in platelet response and a relatively slow onset of action compromise outcomes with clopidogrel. Evidence reviewed in this article shows that in NSTE-ACS patients, ticagrelor and prasugrel are more effective than clopidogrel and are relatively well tolerated, with an acceptable and manageable bleeding risk. The literature suggests several differences between ticagrelor and prasugrel that should allow clinicians to better tailor treatment to the patient. Head-to-head comparisons are now needed to compare directly the risks and benefits of ticagrelor and prasugrel in NSTE-ACS. Further studies also need to address other outstanding issues such as the benefits and risks of prasugrel pre-treatment and to stratify efficacy and tolerability according to diabetes mellitus (DM) and other co-morbidities. In the meantime, the issues discussed in this review should enhance clinicians' ability to optimize and individualize NSTE-ACS treatment, thereby further reducing the morbidity and mortality associated with this common cardiovascular condition.


Asunto(s)
Síndrome Coronario Agudo , Adenosina/análogos & derivados , Electrocardiografía , Piperazinas/farmacología , Activación Plaquetaria/efectos de los fármacos , Tiofenos/farmacología , Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/tratamiento farmacológico , Síndrome Coronario Agudo/metabolismo , Síndrome Coronario Agudo/fisiopatología , Adenosina/agonistas , Adenosina/metabolismo , Adenosina/farmacología , Aspirina/farmacología , Disponibilidad Biológica , Clopidogrel , Investigación sobre la Eficacia Comparativa , Monitoreo de Drogas/métodos , Sinergismo Farmacológico , Quimioterapia Combinada/métodos , Humanos , Farmacovigilancia , Inhibidores de Agregación Plaquetaria/farmacología , Clorhidrato de Prasugrel , Ensayos Clínicos Controlados Aleatorios como Asunto , Receptores Purinérgicos P2Y/metabolismo , Medición de Riesgo , Ticagrelor , Ticlopidina/análogos & derivados , Ticlopidina/farmacología , Resultado del Tratamiento
11.
Thromb Haemost ; 105(6): 1024-31, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21505721

RESUMEN

It was the objective of this study to assess the effect of the implementation of the smoke-free legislation on haemostasis and systemic inflammation in second-hand smoking (SHS)-exposed healthy volunteers. Fibrin-rich clot properties, platelet reactivity and inflammatory biomarkers were measured before and four months following the implementation of the smoke-free legislation in gender and age-matched healthy volunteers exposed (n=23, exposed) and unexposed (n=23, controls) to occupational SHS. The primary objective was to compare fibrin-rich clot stiffness before and after implementation of the smoke-free legislation. There was 40% reduction in fibrin-rich clot stiffness following the implementation of the smoke-free legislation in SHS-exposed volunteers (17 ± 7 vs. 10.6 ± 7 dynes/cm², before and after, respectively, p=0.001). These dramatic changes were associated with a 20% reduction in fibrin fiber density (p<0.01) and a 20% reduction in clot lysis time (p=0.05). No change in fibrin properties was observed in the control group of SHS-unexposed volunteers related to the implementation of the smoke-free legislation. Of interest, neither platelet reactivity nor systemic inflammatory biomarkers were changed in either group. The smoke-free legislation is associated with significant changes in fibrin-rich clot properties toward a less thrombogenic conformation with a better fibrinolysis response while neither platelet reactivity nor systemic inflammatory biomarkers are modified. These improvements may explain the observed reduction in acute coronary syndrome following the implementation of the smoke-free legislation.


Asunto(s)
Síndrome Coronario Agudo/epidemiología , Legislación como Asunto/estadística & datos numéricos , Contaminación por Humo de Tabaco/legislación & jurisprudencia , Síndrome Coronario Agudo/sangre , Síndrome Coronario Agudo/diagnóstico , Síndrome Coronario Agudo/inmunología , Biomarcadores/sangre , Retracción del Coagulo , Fibrinólisis , Francia , Hemostasis , Humanos , Incidencia , Inflamación , Exposición Profesional/efectos adversos , Exposición Profesional/legislación & jurisprudencia , Activación Plaquetaria , Contaminación por Humo de Tabaco/efectos adversos
12.
Heart ; 97(11): 887-91, 2011 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-21421600

RESUMEN

AIM: To determine the incidence, type and possible association with mortality of major bleeding in patients with non-ST segment elevation acute coronary syndrome (NSTE-ACS) treated with an invasive strategy using predominantly the radial approach and triple antiplatelet therapy. METHODS: In the multicentre randomised ABOARD Study, 352 patients with NSTE-ACS were randomised to an 'immediate percutaneous coronary intervention (PCI)' strategy or a strategy of PCI on the 'next working day'. Radial access was predominantly used in this study population. The present subanalysis evaluated the occurrence of major bleeding complications and their association with mortality at 1 month. RESULTS: Patients were treated with a triple antiplatelet therapy using high loading and maintenance doses of clopidogrel and abciximab in 99% of patients receiving PCI. The trans-radial approach was used in the vast majority of patients (84%). During the first 30 days, major bleeding complications (STEEPLE definition) occurred in 5.4% of patients (n=19), with no difference between immediate and delayed intervention. The most common bleeding complications were occult bleeding (36.8% of bleeding, n=7/19) and overt gastrointestinal bleeding (21% of bleeding, n=4/19). Patients with major bleeding had a higher peak concentration of creatinine during hospitalisation (mean±SD, 170±169 vs 97±57 µmol/l; p=0.005) and a 1-month mortality of 26.3%, much higher than patients without bleeding (0.6%, p<0.0001). Major bleeding was strongly associated with 30-day mortality (OR 50.3; 95% CI 10.1 to 249.7; p<0.0001). CONCLUSION: Despite the predominant use of the radial approach, major bleeding (essentially occult and gastrointestinal) remains a common complication, which is highly associated with mortality in patients with NSTE-ACS treated with optimal antithrombotic therapy.


Asunto(s)
Síndrome Coronario Agudo/terapia , Angioplastia Coronaria con Balón/métodos , Hemorragia/inducido químicamente , Inhibidores de Agregación Plaquetaria/efectos adversos , Abciximab , Anciano , Anticuerpos Monoclonales/efectos adversos , Aspirina/efectos adversos , Clopidogrel , Quimioterapia Combinada , Femenino , Humanos , Fragmentos Fab de Inmunoglobulinas/efectos adversos , Masculino , Persona de Mediana Edad , Ticlopidina/efectos adversos , Ticlopidina/análogos & derivados , Resultado del Tratamiento
13.
Hamostaseologie ; 29(4): 339-48, 2009 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-19882081

RESUMEN

The P2Y12 receptor has proven to be a key target in the prevention of complications associated with atherosclerotic vascular disease especially in the context of acute coronary syndrome and percutaneous coronary intervention in addition to aspirin. Three generations of thienopyridines, ticlopidine, clopidogrel, and prasugrel have proven efficacy in the prevention of ischemic vascular events but with increased bleeding. The concept of individualized tailored therapy has recently emerged with the discovery of the diminished effect of some thienopyridine among carriers of the loss-of-function cytochrome (CYP) P4502C19*2 variant. Non-thienopyridine P2Y12 antagonists have also recently demonstrated that these benefits are not limited to one class of agents or may be generalizable to reversible antagonists of this receptor. Future rational use of these agents will require attention to disease and patient features to strike the optimal balance of benefit to risk.


Asunto(s)
Antagonistas del Receptor Purinérgico P2 , Síndrome Coronario Agudo/prevención & control , Adenosina/análogos & derivados , Adenosina/uso terapéutico , Angioplastia Coronaria con Balón , Aspirina/uso terapéutico , Aterosclerosis/complicaciones , Puente de Arteria Coronaria/efectos adversos , Hemorragia/prevención & control , Humanos , Piperazinas/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Complicaciones Posoperatorias/prevención & control , Clorhidrato de Prasugrel , Receptores Purinérgicos P2Y12 , Accidente Cerebrovascular/prevención & control , Tiofenos/uso terapéutico , Ticagrelor
14.
Eur J Neurol ; 16(8): 902-8, 2009 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-19473362

RESUMEN

BACKGROUND AND PURPOSE: Data on current cardiovascular event rates in patients with asymptomatic carotid artery stenosis (ACAS) are sparse. We compared the 1-year outcomes of patients with ACAS > or =70% versus patients without ACAS in an international, prospective cohort of outpatients with or at risk of atherothrombosis. METHODS: The Reduction of Atherothrombosis for Continued Health Registry enrolled patients with either > or =3 atherothrombotic risk factors or established atherothrombotic disease. We investigated the 1-year follow-up data of patients for whom physicians reported presence/absence of ACAS at the time of inclusion. RESULTS: Compared with patients without ACAS (n = 30 329), patients with ACAS (n = 3164) had higher age- and sex-adjusted 1-year rates of transient ischaemic attack (3.51% vs. 1.61%, P < 0.0001), non-fatal stroke (2.65% vs. 1.75%, P = 0.0009), fatal stroke (0.49% vs. 0.26%, P = 0.04), cardiovascular death (2.29% vs. 1.52%, P = 0.002), the composite end-point cardiovascular death/myocardial infarction/stroke (6.03% vs. 4.29%, P < 0.0001) and bleeding events (1.41% vs. 0.81%, P = 0.002). In patients with ACAS, Cox regression analyses identified history of cerebrovascular ischaemic events as most important predictor of future stroke (HR 3.21, 95% CI 1.82-5.65, P < 0.0001). CONCLUSION: Asymptomatic carotid artery stenosis was associated with high 1-year rates of cardiovascular and cerebrovascular ischaemic events. Stroke was powerfully predicted by prior cerebrovascular ischaemic events.


Asunto(s)
Enfermedades Cardiovasculares/epidemiología , Accidente Cerebrovascular/epidemiología , Anciano , Isquemia Encefálica/epidemiología , Estenosis Carotídea/epidemiología , Trastornos Cerebrovasculares/epidemiología , Femenino , Humanos , Masculino , Modelos de Riesgos Proporcionales , Estudios Prospectivos , Sistema de Registros , Factores de Riesgo , Accidente Cerebrovascular/prevención & control
15.
Heart ; 95(3): 211-5, 2009 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18801782

RESUMEN

OBJECTIVE: To test if delay-to-angiography (>72 hours from admission) in patients presenting with high-risk non-ST-elevation acute coronary syndromes (NSTE-ACS) is associated with adverse outcomes. DESIGN: GRACE (Global Registry of Acute Coronary Events) is a multinational registry of patients admitted with NSTE-ACS. SETTING: 14 countries with varying healthcare systems. PATIENTS: 23 396 high-risk NSTE-ACS patients with complete initial data collection entered into GRACE between 1999 and 2006 were analysed. INTERVENTIONS: Data were analysed according to delay-to-angiography and subsequent in-hospital or post-discharge adverse outcomes. MAIN OUTCOME MEASURES: Outcomes recorded included death, myocardial infarction, recurrent ischaemia, stroke, new heart failure and composite major adverse cardiovascular event (MACE) comprising death, cerebrovascular accident and myocardial infarction. Revascularisation procedures were recorded. RESULTS: 10 089 (43.1%) had no in-hospital angiography. Median delay-to-angiography was 46 hours; 3680 (34%) patients waited >72 hours. 9.3% waited >7 days before angiography. Patients waiting longest were more often older, diabetic, women and had a history of heart failure, previous myocardial infarction or hypertension. Recurrent in-hospital ischaemia (33% vs 22%), reinfarction (8.4% vs 5.0%) and heart failure (14% vs 9.1%) were more common with delayed angiography. Delayed angiography was associated with better outcomes than no angiography (MACE 18.9% vs 22.2%, p = 0.015). MACE rates within six months of admission were higher with longer delay-to-angiography and highest of all with no angiography. CONCLUSIONS: High-risk NSTE-ACS is suboptimally managed with 43% not undergoing angiography. One-third of those undergoing angiography are delayed >72 hours. Longer delays were more likely with higher risk, sicker patients. These delays were associated with adverse outcomes at six months. Very long delay was associated with lower MACE, but not mortality, compared to conservative management.


Asunto(s)
Síndrome Coronario Agudo/diagnóstico por imagen , Síndrome Coronario Agudo/terapia , Femenino , Humanos , Masculino , Persona de Mediana Edad , Revascularización Miocárdica , Pautas de la Práctica en Medicina , Pronóstico , Estudios Prospectivos , Calidad de la Atención de Salud , Radiografía , Medición de Riesgo , Factores de Tiempo , Resultado del Tratamiento
16.
Arch Cardiovasc Dis ; 101(4): 220-5, 2008 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-18654096

RESUMEN

INTRODUCTION: Conflicting data exist on the risk of stent thrombosis with drug-eluting stents (DES) versus bare-metal stents (BMS). Little is known about the potential different characteristics and outcomes of DES versus BMS thrombosis. OBJECTIVE: To compare the characteristics, timing and outcomes of patients with angiographic stent thrombosis according to type of stent implanted. METHODS: The population comprised consecutive patients who underwent BMS or DES implantation (January 2003-April 2007) at Pitié-Salpêtrière Hospital. Data from patients with and without a stent thrombosis were compared to identify predictors of thrombosis. Timing of thrombosis (acute,<24 hours; subacute,<30 days; late,>30 days; very late,>1 year), clinical, angiographic and procedural characteristics, and outcomes were compared between patients with a BMS or DES thrombosis. RESULTS: A total of 3579 patients received a BMS (2815 lesions, 2318 patients) or a DES (1536 lesions, 1261 patients). Documented angiographic stent thrombosis occurred in 52 (1.4%) patients, 16 (1.3%) with a DES and 36 (1.6%) with a BMS. Rates of acute (0.1% versus 0.2%), subacute (1% versus 0.7%), late (both 0.2%) and very late (both 0.2%) thrombosis were similar in patients with BMS and DES thrombosis. Factors predictive of stent thrombosis were similar, including left ventricular failure (P<0.0001), initial percutaneous coronary intervention (PCI) for acute myocardial infarction (P<0.0001), multivessel PCI (P<0.0001), and balloon dilatation before stenting (P<0.04). Eleven (21%) cases of BMS (n=8, 22%) or DES (n=3, 19%) thrombosis arose soon after stopping antiplatelet therapy. Thirteen of 52 (25%) patients died a few hours after the event. Twenty-seven (52%) major adverse cardiac events occurred at 18 months, 7 in patients with a DES and 20 in those with a BMS (44% versus 55%, P=NS). These included 16 deaths (31%), 7 repeat PCIs and 4 myocardial infarctions. There were no independent predictive factors of death after stent thrombosis. CONCLUSIONS: BMS and DES thrombosis are similar in terms of timing of thrombosis, characteristics and outcomes, and share the same risk of late thrombosis after interruption of antiplatelet therapy.


Asunto(s)
Angiografía Coronaria , Estenosis Coronaria/terapia , Trombosis Coronaria/diagnóstico por imagen , Stents/efectos adversos , Angioplastia Coronaria con Balón , Cateterismo , Trombosis Coronaria/epidemiología , Trombosis Coronaria/prevención & control , Femenino , Insuficiencia Cardíaca/epidemiología , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/epidemiología , Infarto del Miocardio/terapia , Inhibidores de Agregación Plaquetaria/uso terapéutico , Pronóstico , Diseño de Prótesis , Recurrencia , Retratamiento , Factores Sexuales , Factores de Tiempo
17.
Arch Cardiovasc Dis ; 101(3): 175-80, 2008 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-18477945

RESUMEN

AIMS OF THE STUDY: To assess mortality in people > or =75 years of age 6 months after myocardial infarction complicated by cardiogenic shock and treated by angioplasty with complete revascularisation and optimal anti-thrombotic treatment; to compare results to those of younger patients with or without shock and to analyse predictive factors for death. MATERIALS AND METHODS: The study is based on 1011 consecutive patients with myocardial infarction admitted for primary angioplasty, subdivided into four groups by age and the presence or absence of cardiogenic shock: group 1 (<75 years of age without shock, n=733), group 2 (<75 years of age with shock, n=49), group 3 (> or =75 years of age without shock, n=208) and group 4 (> or =75 years of age with shock, n=20). These four patient groups were compared for mortality rates and predictive factors for in-hospital and 6 month mortality. RESULTS: In-hospital mortality in groups 1 to 4 was 1.7%, 30.6%, 9.1%, and 70% (p<0.0001) respectively and 6-month mortality was 3.1%, 40%, 16% and 78% (P<0.0001). By univariate analysis renal failure was a predictive factor for death at 6 months in patients without cardiogenic shock (groups 1 and 3), and left ventricular function in patients in group 2. No predictive factors were found in group 4 patients. The independent predictive factors for death at 6 months were: age >75 years of age (P<0.0003), cardiogenic shock (P<0.0001), triple vessel lesions (P<0.01) and creatinine clearance (P=0.004). CONCLUSION: Mortality after angioplasty remains high in people > or =75 years with cardiogenic shock despite all the advances in the management of myocardial infarction. These disappointing results should encourage us to assess the role of surgical revascularisation and circulatory assistance.


Asunto(s)
Angioplastia Coronaria con Balón/efectos adversos , Infarto del Miocardio/terapia , Choque Cardiogénico/mortalidad , Factores de Edad , Anciano , Femenino , Francia/epidemiología , Mortalidad Hospitalaria/tendencias , Humanos , Masculino , Infarto del Miocardio/complicaciones , Infarto del Miocardio/mortalidad , Pronóstico , Factores de Riesgo , Choque Cardiogénico/etiología , Tasa de Supervivencia/tendencias
18.
Arch Cardiovasc Dis ; 101(2): 81-8, 2008 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-18398391

RESUMEN

INTRODUCTION: Atherothrombosis is a systemic, diffuse disease associated with a high risk of cardiovascular morbidity and mortality. It is the main cause of death in Western populations, a major public health concern and its prevalence will further increase in the future. OBJECTIVES: To evaluate the rate of major vascular events at 1 year in French patients with confirmed atherothrombotic disease, recruited in the REACH international registry. METHODS: The REACH Registry has recruited 55.000 patients in 44 countries, aged at least 45 years and suffering from established atherothrombotic disease (EAD). In France, 713 investigators selected 3.514 patients with EAD between December 2003 and June 2004. Each investigator had to include 5 to 10 patients presenting after a first documented event of cerebrovascular disease (CVD), coronary artery disease (CAD) or lower limb peripheral arterial occlusive disease (PAD). The patients were followed up for 1 year with collection of major vascular events. RESULTS: Among the 3514 French patients with EAD in the REACH registry, 2.373 (68%) had documented coronary disease, 778 (22%) had an ischemic stroke and 923 (26%) had documented PAD. One quarter of CAD patients, one third of CVD patients and one half of PAD patients had another atherothrombotic disease localization. Follow-up at 1 year was documented for 3.373 patients with EAD. The 1-year event rate in patients who had EAD was a function of the number of atherothrombotic localizations: the vascular death rate was 1.8% if there was a single localization and 4.1% if there were 2 or 3 localizations, and the composite death, infarct and stroke rates were 3.8% and 7.2% respectively and 11.7% and 22.3% respectively if hospitalizations were added to the latter endpoint. CONCLUSION: The number of major vascular events during the first year is high in EAD patients although these patients were followed up on an outpatient basis and are considered to be stable. In patients with prior EAD, there was a close link between the incidence of major vascular events and the number of symptomatic arterial beds (2 or 3 sites). The risk of a major vascular event was twice as high in patients with polyvascular involvement than in those who only had one affected artery.


Asunto(s)
Aterosclerosis/complicaciones , Trastornos Cerebrovasculares/epidemiología , Enfermedad de la Arteria Coronaria/epidemiología , Enfermedades Vasculares Periféricas/epidemiología , Sistema de Registros , Trombosis/complicaciones , Anciano , Aterosclerosis/tratamiento farmacológico , Trastornos Cerebrovasculares/etiología , Enfermedad de la Arteria Coronaria/etiología , Femenino , Francia/epidemiología , Humanos , Inhibidores de Hidroximetilglutaril-CoA Reductasas/uso terapéutico , Masculino , Persona de Mediana Edad , Enfermedades Vasculares Periféricas/etiología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Estudios Prospectivos , Accidente Cerebrovascular/epidemiología , Trombosis/tratamiento farmacológico
19.
Ann Cardiol Angeiol (Paris) ; 56(6): 250-6, 2007 Dec.
Artículo en Francés | MEDLINE | ID: mdl-17963716

RESUMEN

Treatment of intracoronary thrombus is well documented. Three situations should be differentiated Primary percutaneous coronary intervention for early STEMI presenters is the most frequent one. Glycoprotein IIb/IIIa inhibitors are the gold standard antithrombotic treatment with a clear mortality benefit with abciximab. Thrombectomy with simple to use devices is another attractive option for interventionalists, although there is no clear established clinical benefit. Rescue PCI following failed thrombolysis is a more complicated situation given the underlying bleeding risk that is difficult to evaluate. The second situation is when a thrombus appears during an elective PCI. Although much less frequent than primary PCI, it is more often related to a lack of identification of the risk, to an inappropriate choice of the materials or to a non-optimal upstream antithrombotic treatment. A careful identification of all potential relevant causes is the key point of the management strategy. Post-PCI rethrombosis is the third situation and probably the less frequent. However, it is the most difficult to deal with.


Asunto(s)
Síndrome Coronario Agudo/terapia , Angioplastia Coronaria con Balón , Trombosis Coronaria/terapia , Abciximab , Anticuerpos Monoclonales/uso terapéutico , Fibrinolíticos/uso terapéutico , Hemorragia/prevención & control , Humanos , Fragmentos Fab de Inmunoglobulinas/uso terapéutico , Inhibidores de Agregación Plaquetaria/uso terapéutico , Complejo GPIIb-IIIa de Glicoproteína Plaquetaria/antagonistas & inhibidores , Medición de Riesgo , Stents , Trombectomía , Resultado del Tratamiento
20.
Ann Cardiol Angeiol (Paris) ; 56 Suppl 1: S21-8, 2007 Jun.
Artículo en Francés | MEDLINE | ID: mdl-17719354

RESUMEN

The clinical benefit of the combination of aspirin plus clopidogrel over aspirin alone to prevent recurrent events after acute coronary syndrome is obviously a key step of the past few years in the management of coronary artery disease. The extended benefit of this combination among patients undergoing stent implantation is another key message for clinician. The consistent benefit of the dual oral antiplatelet therapy in all clinical trials is reassuring for clinicians. However, all well designed clinical trials generate new hypothesis and unsolved clinical issues. The loading dose of clopidogrel and whether we should monitor the biological response to clopidogrel in order to improve its clinical benefit are the next clinical challenges for clinicians dealing with acute coronary syndromes. Providing adequate answers to these relevant clinical issues should improve the clinical benefit of clopidogrel. All these important points are discussed in the following manuscript.


Asunto(s)
Síndrome Coronario Agudo/terapia , Angioplastia Coronaria con Balón , Aspirina/uso terapéutico , Ensayos Clínicos como Asunto , Clopidogrel , Trombosis Coronaria/prevención & control , Quimioterapia Combinada , Humanos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Ticlopidina/análogos & derivados , Ticlopidina/uso terapéutico
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