RESUMEN
Heart failure (HF) has high event rates, mortality, and is challenging to manage in clinical practice. Clinical management is complicated by complex therapeutic strategies in a population with a high prevalence of comorbidity and general frailty. In the last four years, an abundance of research has become available to support multidisciplinary management of heart failure from within the hospital through to discharge and primary care as well as supporting diagnosis and comorbidity management. Within the hospital setting, recent evidence supports sacubitril-valsartan combination in frail, deteriorating or de novo patients with LVEF≤40%. Furthermore, new strategies such as SGLT2 inhibitors and vericiguat provide further benefit for patients with decompensating HF. Studies with tafamidis report major clinical benefits specifically for patients with ATTR cardiac amyloidosis, a remaining underdiagnosed and undertreated disease. New evidence for medical interventions supports his bundle pacing to reduce QRS width and improve haemodynamics as well as ICD defibrillation for non-ischemic cardiomyopathy. The Mitraclip reduces hospitalisations and mortality in patients with symptomatic, secondary mitral regurgitation and ablation reduces mortality and hospitalisations in patients with paroxysmal and persistent atrial fibrillation. In end-stage HF, the 2018 French Heart Allocation policy should improve access to heart transplants for stable, ambulatory patients and, mechanical circulatory support should be considered to avoid deteriorating on the waiting list. In the community, new evidence supports that improving discharge education, treatment and patient support improves outcomes. The authors believe that this review fills the gap between the guidelines and clinical practice and provides practical recommendations to improve HF management.
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Insuficiencia Cardíaca , Alta del Paciente , Aminobutiratos , Compuestos de Bifenilo , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/terapia , Hospitalización , Hospitales , HumanosRESUMEN
BACKGROUND: Male hypogonadism, arising from a range of etiologies including androgen-deprivation therapies (ADTs), has been reported as a risk factor for acquired long-QT syndrome (aLQTS) and torsades de pointes (TdP). A full description of the clinical features of aLQTS associated with ADT and of underlying mechanisms is lacking. METHODS: We searched the international pharmacovigilance database VigiBase for men (n=6 560 565 individual case safety reports) presenting with aLQTS, TdP, or sudden death associated with ADT. In cardiomyocytes derived from induced pluripotent stem cells from men, we studied electrophysiological effects of ADT and dihydrotestosterone. RESULTS: Among subjects receiving ADT in VigiBase, we identified 184 cases of aLQTS (n=168) and/or TdP (n=68; 11% fatal), and 99 with sudden death. Of the 10 ADT drugs examined, 7 had a disproportional association (reporting odds ratio=1.4-4.7; P<0.05) with aLQTS, TdP, or sudden death. The minimum and median times to sudden death were 0.25 and 92 days, respectively. The androgen receptor antagonist enzalutamide was associated with more deaths (5430/31 896 [17%]; P<0.0001) than other ADT used for prostate cancer (4208/52 089 [8.1%]). In induced pluripotent stem cells, acute and chronic enzalutamide (25µM) significantly prolonged action potential durations (action potential duration at 90% when paced at 0.5Hz; 429.7±27.1 (control) versus 982.4±33.2 (acute, P<0.001) and 1062.3±28.9ms (chronic; P<0.001), and generated afterdepolarizations and/or triggered activity in drug-treated cells (11/20 acutely and 8/15 chronically). Enzalutamide acutely and chronically inhibited delayed rectifier potassium current, and chronically enhanced late sodium current. Dihydrotestosterone (30nM) reversed enzalutamide electrophysiological effects on induced pluripotent stem cells. CONCLUSION: QT prolongation and TdP are a risk in men receiving enzalutamide and other ADTs. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT03193138.
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Dihidrotestosterona/farmacología , Miocitos Cardíacos/efectos de los fármacos , Función Ventricular/efectos de los fármacos , Andrógenos/farmacología , Andrógenos/uso terapéutico , Diferenciación Celular/efectos de los fármacos , Diferenciación Celular/fisiología , Células Cultivadas , Bases de Datos Factuales , Muerte Súbita Cardíaca/epidemiología , Dihidrotestosterona/uso terapéutico , Fenómenos Electrofisiológicos/efectos de los fármacos , Eunuquismo/tratamiento farmacológico , Eunuquismo/epidemiología , Eunuquismo/fisiopatología , Ventrículos Cardíacos/efectos de los fármacos , Ventrículos Cardíacos/fisiopatología , Humanos , Células Madre Pluripotentes Inducidas/efectos de los fármacos , Células Madre Pluripotentes Inducidas/fisiología , Internacionalidad , Síndrome de QT Prolongado/inducido químicamente , Síndrome de QT Prolongado/epidemiología , Síndrome de QT Prolongado/patología , Síndrome de QT Prolongado/fisiopatología , Masculino , Potenciales de la Membrana/efectos de los fármacos , Miocitos Cardíacos/patología , Farmacovigilancia , Torsades de Pointes/inducido químicamente , Torsades de Pointes/epidemiología , Torsades de Pointes/patología , Torsades de Pointes/fisiopatología , Investigación Biomédica TraslacionalRESUMEN
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 â¼12% 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.
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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/farmacologíaRESUMEN
OBJECTIVES: Benefits of hydroxychloroquine (HCQ) use on physician reported outcomes are well documented in systemic lupus erythematosus (SLE). We assess for the first time the association and predictive value of blood HCQ levels towards health-related quality of life (HRQOL) in SLE. METHODS: Data from the PLUS study (a randomized, double-blind, placebo-controlled, multicentre study) were utilized. Blood HCQ levels were quantified by high-performance liquid chromatography along with HRQOL assessments (Medical Outcomes Study-SF-36) at baseline (V1) and month 7 (V2). RESULTS: 166 SLE patients' data were analysed. Mean (SD) age and disease duration were 44.4 (10.7) and 9.3 (6.8) years. Eighty-seven per cent were women. Mean (SD, median, IQR) HCQ concentrations in the blood at V1 were 660 (314, 615, 424) ng/ml and increased to 1020 (632, 906, 781) ng/ml at V2 (mean difference 366 units, 95% confidence interval -472 to -260, p < 0.001). No significant correlations between HCQ concentrations with HRQOL domains at V1 or V2 were noted. There were no differences in HRQOL stratified by HCQ concentrations. HCQ concentrations at V1 or changes in HCQ concentration (V2-V1) were not predictive of HRQOL at V2 or changes in HRQOL (V2-V1). CONCLUSIONS: No association of HCQ concentrations with current or longitudinal HRQOL were found in SLE.
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Antirreumáticos/sangre , Hidroxicloroquina/sangre , Lupus Eritematoso Sistémico/sangre , Calidad de Vida , Adulto , Método Doble Ciego , Femenino , Francia , Humanos , Modelos Lineales , Masculino , Persona de Mediana EdadRESUMEN
INTRODUCTION: Pharmacogenetics aims to identify the underlying genetic factors participating in the variability of drug response. Indeed, genetic variability at the DNA or RNA levels can directly or indirectly modify the pharmacokinetic or the pharmacodynamic parameters of a drug. The ultimate aim of pharmacogenetics is to move towards a personalised medicine by predicting responders and non-responders, adjusting the dose of the treatment, and identifying individuals at risk of adverse drug effects. METHODS: A literature research was performed in which we reviewed all pharmacogenetic studies in neurological disorders including neurodegenerative diseases, multiple sclerosis, stroke and epilepsy. RESULTS: Several pharmacogenetic studies have been performed in neurology, bringing insights into the inter-individual drug response variability and in the pathophysiology of neurological diseases. The principal implications of these studies for the management of patients in clinical practice are discussed. CONCLUSION/DISCUSSION: Although several genetic factors have been identified in the modification of drug response in neurological disorders, most of them have a marginal predictive effect at the single gene level, suggesting mutagenic interactions as well as other factors related to drug interaction and disease subtypes. Most pharmacogenetic studies deserve further replication in independent populations and, ideally, in pharmacogenetic clinical trials to demonstrate their relevance in clinical practice.
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Enfermedades del Sistema Nervioso/tratamiento farmacológico , Enfermedades del Sistema Nervioso/genética , Farmacogenética/métodos , Trastornos Heredodegenerativos del Sistema Nervioso/genética , HumanosRESUMEN
OBJECTIVE: Blood concentrations of hydroxychloroquine (HCQ) vary widely among patients with systemic lupus erythematosus (SLE). A pharmacokinetic/pharmacodynamic relationship has been found in different situations, and a very low blood concentration of HCQ is a simple marker of nonadherence to treatment. Therefore, interest in blood HCQ concentration measurement has increased, but little is known about factors that influence blood HCQ concentration variability. This study was undertaken to analyze determinants of blood HCQ concentrations. METHODS: We conducted a retrospective analysis of patient data, including data from the Plaquenil Lupus Systemic (PLUS) study, to determine the association of epidemiologic, clinical, and biologic factors with blood HCQ concentrations. Data for nonadherent patients (blood HCQ concentration <200 ng/ml) were excluded. RESULTS: To examine homogeneous pharmacologic data, we restricted the analyses of the PLUS data to the 509 SLE patients receiving 400 mg/day. We found no association of ethnicity or smoking with blood HCQ concentrations and no pharmacokinetic drug-drug interaction with antacids or with inhibitors or inducers of cytochrome P450 enzymes. On multivariate analysis, high body mass index (P = 0.008), no treatment with corticosteroids (P = 0.04), increased time between the last tablet intake and measurement of blood HCQ concentrations (P = 0.017), low platelet count (P < 0.001), low neutrophil count (P < 0.001), and high estimated creatinine clearance (P < 0.001) were associated with low blood HCQ concentrations. In 22 SLE patients with chronic renal insufficiency (median serum creatinine clearance 52 ml/minute [range 23-58 ml/minute]) who received 400 mg/day HCQ, the median blood HCQ concentration was significantly higher than that in the 509 patients from the PLUS study (1,338 ng/ml [range 504-2,229 ng/ml] versus 917 ng/ml [range 208-3316 ng/ml]) (P < 0.001). CONCLUSION: We provide a comprehensive analysis of determinants of blood HCQ concentrations. Because this measurement is increasingly being used, these data might be useful for clinicians.
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Corticoesteroides/uso terapéutico , Antirreumáticos/farmacocinética , Hidroxicloroquina/farmacocinética , Lupus Eritematoso Sistémico/tratamiento farmacológico , Adulto , Antirreumáticos/sangre , Antirreumáticos/uso terapéutico , Índice de Masa Corporal , Creatinina/sangre , Femenino , Humanos , Hidroxicloroquina/sangre , Hidroxicloroquina/uso terapéutico , Recuento de Leucocitos , Lupus Eritematoso Sistémico/sangre , Lupus Eritematoso Sistémico/complicaciones , Masculino , Persona de Mediana Edad , Análisis Multivariante , Neutrófilos/citología , Obesidad/complicaciones , Insuficiencia Renal Crónica/complicaciones , Estudios Retrospectivos , Trombocitopenia , Factores de Tiempo , Adulto JovenRESUMEN
Cytochrome P450 (CYP)2C19 catalyzes the bioactivation of the antiplatelet prodrug clopidogrel, and CYP2C19 loss-of-function alleles impair formation of active metabolites, resulting in reduced platelet inhibition. In addition, CYP2C19 loss-of-function alleles confer increased risks for serious adverse cardiovascular (CV) events among clopidogrel-treated patients with acute coronary syndromes (ACSs) undergoing percutaneous coronary intervention (PCI). Guideline updates include emphasis on appropriate indication for CYP2C19 genotype-directed antiplatelet therapy, refined recommendations for specific CYP2C19 alleles, and additional evidence from an expanded literature review (updates at http://www.pharmgkb.org).
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Hidrocarburo de Aril Hidroxilasas/genética , Inhibidores de Agregación Plaquetaria/farmacocinética , Ticlopidina/análogos & derivados , Clopidogrel , Citocromo P-450 CYP2C19 , Pruebas Genéticas , Variación Genética , Genotipo , Humanos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Medición de Riesgo , Ticlopidina/farmacocinética , Ticlopidina/uso terapéuticoAsunto(s)
Bases de Datos Genéticas , Registros Electrónicos de Salud/organización & administración , Genómica/organización & administración , Farmacogenética/organización & administración , Medicina de Precisión/métodos , Sistemas de Apoyo a Decisiones Clínicas/organización & administración , Femenino , Pruebas Genéticas , Personal de Salud , Humanos , Masculino , Persona de Mediana Edad , Evaluación de Procesos y Resultados en Atención de SaludRESUMEN
To determine CYP2C19 and CYP2C8 allele frequencies, 28 coding and/or functional variants were genotyped in 1250 African-American, Asian, Caucasian, Hispanic and Ashkenazi Jewish (AJ) individuals. The combined CYP2C19 variant allele frequencies ranged from â¼0.30 to 0.41; however, the CYP2C8 frequencies were much lower (â¼0.04-0.13). After incorporating previously reported CYP2C9 genotyping results from these populations (36 total CYP2C variants), 16 multi-ethnic CYP2C haplotypes were inferred with frequencies >0.5%. Notably, the 2C19*17-2C9*1-2C8*2 haplotype was identified among African-Americans (8%) and Hispanics (2%), indicating that CYP2C19*17 does not always tag a CYP2C haplotype that encodes efficient CYP2C-substrate metabolism. The 2C19*1-2C9*2-2C8*3 haplotype was identified in all populations except African-Americans and additional novel haplotypes were identified in selected populations (for example, 2C19*2-2C9*1-2C8*4 and 2C19*4B-2C9*1-2C8*1), together indicating that both CYP2C19*17 and *2 can be linked with other CYP2C loss-of-function alleles. These results have important implications for pharmacogenomic association studies involving the CYP2C locus and are clinically relevant when administering CYP2C-substrate medications.
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Hidrocarburo de Aril Hidroxilasas/genética , Frecuencia de los Genes , Haplotipos/genética , Pueblo Asiatico/genética , Población Negra/genética , Citocromo P-450 CYP2C19 , Citocromo P-450 CYP2C8 , Genotipo , Humanos , Población Blanca/genéticaRESUMEN
Human multidrug resistance-related protein 2 (MRP2, encoded by ABCC2) is involved in the transport of anionic drugs such as methotrexate (MTX). We prospectively investigated the influence of four common ABCC2 genetic variants (rs717620, rs2273697, rs8187694 and rs8187710) on MTX pharmacokinetics parameters. MTX concentrations were monitored in 50 patients with lymphoid malignancy (27 males; mean age: 53±17 years) receiving high-dose MTX (5.13±1.88 g m(-)(2) in a 4-h perfusion). The population pharmacokinetics modelling showed that ABCC2 -24T allele (rs717620) had a combined influence on both MTX elimination and distribution. The MTX clearance and distribution volume were significantly higher in carriers of at least one copy of the -24T allele as compared with noncarriers: 8.6±2.2 vs 6.7± 2.5 l h(-1), P<0.01 and 30.7±7.7 vs 22.1±8.8 l, P<0.001, respectively. Consequently, -24T allele carriers were more prone to reach MTX nontoxic levels, 48 h after administration.
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Antimetabolitos Antineoplásicos/farmacocinética , Linfoma/tratamiento farmacológico , Metotrexato/farmacocinética , Proteínas Asociadas a Resistencia a Múltiples Medicamentos/genética , Polimorfismo de Nucleótido Simple , Adulto , Anciano , Anciano de 80 o más Años , Secuencia de Bases , Cartilla de ADN , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Linfoma/clasificación , Masculino , Metotrexato/uso terapéutico , Persona de Mediana Edad , Proteína 2 Asociada a Resistencia a Múltiples Medicamentos , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Adulto JovenRESUMEN
Although progress in conventional treatments is making steady and incremental gains to reduce mortality associated with heart failure (HF), there remains a need to explore potentially new therapeutic approaches. HF induced by different etiologies such as coronary artery disease, hypertension, diabetes, infection or inflammation results generally in calcium cycling dysregulation at the myocyte level. Recent advances in understanding of the molecular basis of these calcium cycling abnormalities, together with the evolution of increasingly efficient gene transfer technology, has placed HF within the reach of gene-based therapy. Furthermore, the recent successful completion of a phase 2 trial targeting the sarcoplasmic reticulum calcium pump ushers in a new era for gene therapy for the treatment of HF.
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Terapia Genética/métodos , Insuficiencia Cardíaca/terapia , ATPasas Transportadoras de Calcio del Retículo Sarcoplásmico/genética , Animales , Ensayos Clínicos como Asunto , Marcación de Gen/métodos , Técnicas de Transferencia de Gen , HumanosAsunto(s)
Hidrocarburo de Aril Hidroxilasas/genética , Farmacogenética/métodos , Inhibidores de Agregación Plaquetaria/uso terapéutico , Ticlopidina/análogos & derivados , Síndrome Coronario Agudo/terapia , Alelos , Angioplastia Coronaria con Balón/métodos , Hidrocarburo de Aril Hidroxilasas/metabolismo , Clopidogrel , Citocromo P-450 CYP2C19 , Genotipo , Humanos , Inhibidores de Agregación Plaquetaria/efectos adversos , Inhibidores de Agregación Plaquetaria/metabolismo , Ticlopidina/efectos adversos , Ticlopidina/metabolismo , Ticlopidina/uso terapéuticoAsunto(s)
2-Piridinilmetilsulfinilbencimidazoles/administración & dosificación , Hidrocarburo de Aril Hidroxilasas/genética , Inhibidores de Agregación Plaquetaria/administración & dosificación , Agregación Plaquetaria/efectos de los fármacos , Polimorfismo Genético , Inhibidores de la Bomba de Protones/administración & dosificación , Ticlopidina/análogos & derivados , Adulto , Hidrocarburo de Aril Hidroxilasas/antagonistas & inhibidores , Hidrocarburo de Aril Hidroxilasas/metabolismo , Clopidogrel , Citocromo P-450 CYP2C19 , Relación Dosis-Respuesta a Droga , Interacciones Farmacológicas , Heterocigoto , Homocigoto , Humanos , Lansoprazol , Masculino , Fenotipo , Inhibidores de Agregación Plaquetaria/metabolismo , Ticlopidina/administración & dosificación , Ticlopidina/metabolismo , Adulto JovenAsunto(s)
Síndrome Coronario Agudo/tratamiento farmacológico , Hidrocarburo de Aril Hidroxilasas/genética , Ticlopidina/análogos & derivados , Anciano , Alelos , Plaquetas/efectos de los fármacos , Clopidogrel , Citocromo P-450 CYP2C19 , Femenino , Humanos , Masculino , Persona de Mediana Edad , Inhibidores de Agregación Plaquetaria/farmacología , Inhibidores de Agregación Plaquetaria/uso terapéutico , Estudios Retrospectivos , Ticlopidina/farmacología , Ticlopidina/uso terapéutico , Resultado del TratamientoRESUMEN
Enoxaparin is frequently prescribed for pregnant women who are at high risk for thromboembolic complications. We conducted a population pharmacokinetics study with 75 pregnant women and 38 nonpregnant women as controls to evaluate enoxaparin pharmacokinetics during pregnancy and the postpartum period. Clearance of the drug was higher in the pregnant women throughout pregnancy when compared with nonpregnant women (0.78 +/- 0.03 l/h vs. 0.52 +/- 0.03 l/h, respectively P < 0.001) with the stage of the pregnancy having no influence. The volume of distribution was influenced by stage of the pregnancy, characterized by a two-step increase, with an initial rise paralleling the woman's increase in body weight during the first two trimesters, followed by an additional increase of 41% during the last 2 months of pregnancy, independent of changes in weight. Using enoxaparin pharmacokinetic parameters to simulate anti-Xa time profiles, we observed that the maintenance of the same doses throughout pregnancy resulted in a progressive reduction in mean and peak anti-Xa activities. We recommend the administration of doses normalized for body weight changes so as to counteract enoxaparin pharmacokinetic changes that accompany various stages of pregnancy.
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Anticoagulantes/farmacocinética , Anticoagulantes/uso terapéutico , Enoxaparina/farmacocinética , Enoxaparina/uso terapéutico , Periodo Posparto/metabolismo , Complicaciones Hematológicas del Embarazo/prevención & control , Trombosis de la Vena/prevención & control , Adulto , Femenino , Edad Gestacional , Humanos , Tasa de Depuración Metabólica , Embarazo , Distribución TisularAsunto(s)
Hidrocarburo de Aril Hidroxilasas/genética , Sistema Enzimático del Citocromo P-450/genética , Oxigenasas de Función Mixta/genética , Inhibidores de Agregación Plaquetaria/farmacología , Polimorfismo Genético , Ticlopidina/análogos & derivados , Alelos , Clopidogrel , Citocromo P-450 CYP2C19 , Citocromo P-450 CYP3A , Genotipo , Humanos , Mutación , Adhesividad Plaquetaria , Pruebas de Función Plaquetaria , Isoformas de Proteínas , Análisis de Regresión , Ticlopidina/farmacología , Factores de Tiempo , Resultado del TratamientoRESUMEN
PURPOSE: Recent end point trials of lipid-lowering drugs have shown that patients at very high-risk for coronary disease benefit from treatments that lowers low density lipoprotein cholesterol (LDL cholesterol) plasma levels< or =70 mg/dl and that patients with at least 2 risk factors benefit from LDL cholesterol levels< or =100 mg/dl. Epidemiologic studies have shown that the concentration of high density lipoprotein cholesterol (HDL cholesterol) is a strong, independent, inverse predictor of coronary disease risk. Innovative pharmacological approaches to raise low HDL cholesterol levels are currently of considerable interest, especially for patients with type 2 diabetes or metabolic syndrome. RESULTS: Rosuvastatin has shown superior efficacy in lowering LDL cholesterol, although evidence of clinical benefit is actually lacking. Ezetimibe is a lipid-lowering drug that inhibits absorption of dietary and biliary cholesterol. Its co-administration with statin has given very interesting results. Niacin is the most effective of currently available options for raising HDL cholesterol, although tolerability can be an issue, with serious side effects such as loss of glucose control and liver toxicity. Flushing may occur in 80% of treated patients. Two CETP inhibitors have shown therapeutical efficacy to raise HDL cholesterol, but clinical benefit remains uncertain.
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Dislipidemias/tratamiento farmacológico , Anticolesterolemiantes/uso terapéutico , Enfermedades Cardiovasculares/prevención & control , HDL-Colesterol/sangre , LDL-Colesterol/sangre , HumanosRESUMEN
OBJECTIVE: The antimalarial agents chloroquine (CQ) and hydroxychloroquine (HCQ) are used in long-term treatment of connective tissue diseases (CTDs). A high incidence of heart conduction disorders, including bundle-branch block and incomplete or complete atrioventricular block, has been observed among patients treated with CQ. Since no data were available for HCQ, we studied electrocardiograms (ECGs) in 85 unselected patients with CTD treated with HCQ as the sole antimalarial. METHODS: Eighty-five unselected out-patients treated with HCQ for a minimum of 1 yr, and without established cardiac diseases had standard 12-lead ECGs. RESULTS: Two incomplete right bundle-branch blocks and one left bundle-branch block were observed. No atrioventricular block was observed. The mean PR interval was 137 +/- 20 ms (range 99-188). The mean QTc interval was 410 ms (range 349-464). The mean heart rate was 73 beats/min (range 53-102). CONCLUSION: PR interval, QTc interval and heart rate were not different from normal values. The rate of heart conduction disorders was similar to what is expected in the general population, and contrasted with prior results in CQ-treated patients. Our results add further evidence on the safety of HCQ compared with CQ.
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Antimaláricos/efectos adversos , Antirreumáticos/efectos adversos , Enfermedades del Tejido Conjuntivo/tratamiento farmacológico , Bloqueo Cardíaco/inducido químicamente , Hidroxicloroquina/efectos adversos , Adolescente , Adulto , Anciano , Antimaláricos/uso terapéutico , Antirreumáticos/uso terapéutico , Bloqueo de Rama/inducido químicamente , Electrocardiografía/efectos de los fármacos , Femenino , Estudios de Seguimiento , Sistema de Conducción Cardíaco/efectos de los fármacos , Humanos , Hidroxicloroquina/uso terapéutico , Lupus Eritematoso Sistémico/tratamiento farmacológico , Masculino , Persona de Mediana EdadAsunto(s)
Hidroxicloroquina/sangre , Lupus Eritematoso Sistémico/tratamiento farmacológico , Cromatografía Líquida de Alta Presión , Método Doble Ciego , Humanos , Hidroxicloroquina/administración & dosificación , Hidroxicloroquina/uso terapéutico , Lupus Eritematoso Sistémico/sangre , Cooperación del Paciente , Ensayos Clínicos Controlados Aleatorios como Asunto , Factores de TiempoRESUMEN
We report the case of an association of IgA nephropathy and tuberculosis with superimposed vasculitis lesions on the renal biopsy. Three previous cases of the same association are discussed. The nephropathy had a favorable course in all of these cases on antituberculous treatment only. Tuberculosis is another infection related to IgA nephropathy.