Análisis del proceso de prescripción de inhibidores PCSK9 en los servicios de cardiología de los hospitales españoles y propuesta de optimización. Estudio IKIGAI / Analysis of the prescription process of PCSK9 inhibitors in the cardiology departments of Spanish hospitals and optimization proposal. The IKIGAI study

Objetivos: Conocer las tramitaciones y gestiones requeridas en la prescripción del tratamiento con inhibidores PCSK9 en los servicios de cardiología de los hospitales españoles, haciendo propuestas de mejoras para optimizar el proceso de prescripción. Métodos: Una primera fase de recogida de información sobre variables y procedimientos administrativos requeridos en la prescripción de inhibidores PCSK9 y elaboración de un cuestionario específico. Una segunda fase de recogida de datos a través de un cuestionario electrónico autoadministrado. Resultados: Participaron 88 hospitales (número medio de camas 625; número medio de cardiólogos 18 ± 10; 78% hospitales universitarios). Hubo una infrautilización de inhibidores PCSK9 (prescripción real 30 tratamientos/año; prescripción potencial 80), principalmente por no cumplir con informe de posicionamiento terapéutico (52%), con la denegación de solicitud en un 31%. Se requirieron una media de 1,2 ± 0,4 formularios, con un promedio de 8,5 ± 4,2 variables, además de los requisitos del informe de posicionamiento terapéutico. Solo en el 21% de los hospitales no es necesario un proceso de autorización previa, y en el resto es necesaria la aprobación por una comisión. El tiempo acumulado en el proceso de prescripción es de seis semanas. La discontinuación del tratamiento durante el seguimiento es de 9 ± 12%. Conclusiones: Los inhibidores PCSK9 se encuentran claramente infrautilizados en España. Esto se debe a una incorrecta identificación de los pacientes, y a la existencia de complejos procedimientos de tipo administrativo que podrían inhibir/desmotivar su prescripción por parte de los cardiólogos, y consecuentemente, limitar su prescripción. Asimismo, existe un retraso notable desde la aprobación del fármaco hasta su administración.(AU)

Aims: To ascertain the formalities and procedures required for the prescription of PCSK9 inhibitors in the cardiology departments of Spanish hospitals, making proposals for improvement to optimize the prescription process. Methods: A first phase of collecting information about the variables and administrative procedures required for the prescription of PCK9 inhibitors and the elaboration of a specific questionnaire and a second phase of collecting data with an online self-administered questionnaire. Results: A total of 88 hospitals participated in the study (mean number of beds 625; mean number of cardiologists 18 ± 10; 78% university hospitals). There was underuse of PCSK9 inhibitors (real prescription of 30 treatments/year; potential prescription of 80), mainly because of not fulfilling the therapeutic positioning report (52%) and application refusal (31%). Beyond the requirements of the therapeutic positioning report, 1.2 ± 0.4 applications are required with 8.5 ± 4.2 variables. Only 21% of hospitals did not require a previous authorization process and in the remaining hospitals, approval from a committee was necessary. The accumulated time of the prescription process was 6 weeks. Discontinuation rates during follow-up were 9% ± 12%. Conclusions: Treatment with PCSK9 inhibitors is clearly underused in Spain. This is mainly due to both inappropriate identification of patients, and complex administrative procedures that could inhibit/discourage prescription by cardiologists and consequently, limit their use. In addition, there is a substantial delay from drug approval tadministration.(AU)

Analysis of the prescription process of PCSK9 inhibitors in the cardiology departments of Spanish hospitals and optimization proposal. The IKIGAI study. / Análisis del proceso de prescripción de inhibidores PCSK9 en los servicios de cardiología de los hospitales españoles y propuesta de optimización. Estudio IKIGAI.

AIMS: To ascertain the formalities and procedures required for the prescription of PCSK9 inhibitors in the cardiology departments of Spanish hospitals, making proposals for improvement to optimize the prescription process. METHODS: A first phase of collecting information about the variables and administrative procedures required for the prescription of PCK9 inhibitors and the elaboration of a specific questionnaire and a second phase of collecting data with an online self-administered questionnaire. RESULTS: A total of 88 hospitals participated in the study (mean number of beds 625; mean number of cardiologists 18 ± 10; 78% university hospitals). There was underuse of PCSK9 inhibitors (real prescription of 30 treatments/year; potential prescription of 80), mainly because of not fulfilling the therapeutic positioning report (52%) and application refusal (31%). Beyond the requirements of the therapeutic positioning report, 1.2 ± 0.4 applications are required with 8.5 ± 4.2 variables. Only 21% of hospitals did not require a previous authorization process and in the remaining hospitals, approval from a committee was necessary. The accumulated time of the prescription process was 6 weeks. Discontinuation rates during follow-up were 9% ± 12%. CONCLUSIONS: Treatment with PCSK9 inhibitors is clearly underused in Spain. This is mainly due to both inappropriate identification of patients, and complex administrative procedures that could inhibit/discourage prescription by cardiologists and consequently, limit their use. In addition, there is a substantial delay from drug approval tadministration.

Evaluación del desarrollo infantil en niños menores de 1 año en una unidad médica / Evaluation of child development in children under 1 year in a medical unita

Introducción: el desarrollo psicomotor es un fenómeno de adquisición continua y progresiva de habilidades a lo largo de la infancia, afectado por la herencia genética y factores psicosociales y biológicos. Objetivo: evaluar el desarrollo infantil en niños menores de 1 año mediante la prueba Evaluación del Desarrollo Infantil en una unidad de medicina familiar. Metodología: estudio descriptivo con 62 niños menores de 1 año, en el módulo de PREVENIMSS, de octubre de 2018 a octubre de 2019. Se realizó un muestreo no probabilístico. Para el análisis de los datos se utilizó estadística descriptiva (media, desviación estándar, frecuencias y porcentajes); el análisis inferencial se realizó mediante la prueba de ji al cuadrado, considerando como significancia estadística p < 0.05. Resultados: el 42% (26) fueron niños y el 58% (36) niñas. En el resultado global, el 68% (42) obtuvieron desarrollo normal, el 29% (18) rezago en el desarrollo y el 3% (2) riesgo de retraso en el desarrollo. Las áreas del desarrollo afectadas fueron motricidad fina y lenguaje. Conclusiones: es necesario implementar estrategias institucionales para que se cumplan las políticas públicas de la primera infancia y que todos los niños derechohabientes del Instituto Mexicano del Seguro Social cuenten con evaluaciones periódicas de su desarrollo.

Introduction: Psychomotor development is a phenomenon of continuous and progressive acquirement of skills throughout childhood, affected by genetic inheritance and psychosocial and biological factors. Objective: To evaluate child development to children under 1 year old, through the Child Development Assessment test in a family medicine unit. Methods: Descriptive study in 62 children under 1 year of age, in the PREVENIMSS module, from October 2018 to October 2019. A non-probability sampling was carried out. Descriptive statistics (mean, standard deviation, frequencies and percentages) were used for data analysis, inferential analysis was performed using Chi Square, statistical significance of p < 0.05. Results: 42% (26) were men and 58% (36) women. In the overall result: 68% (42) obtained normal development, 29% (18) lag in development and 3% (2) risk of delay in development. The developmental areas affected were fine motor skills and language. Conclusions: It is necessary to implement institutional strategies so that early childhood public policies are complied with and that all IMSS eligible children have periodic evaluations of their development.

La consulta telemática para el cardiólogo clínico en tiempos de la COVID-19: presente y futuro. Documento de consenso de la Sociedad Española de Cardiología / Telemedicine consultation for the clinical cardiologists in the era of COVID-19: present and future. Consensus document of the Spanish Society of Cardiology

La pandemia producida por la infección por el coronavirus SARS-CoV-2 (COVID-19) ha cambiado la forma de entender nuestras consultas. Para reducir el riesgo de contagio de los pacientes más vulnerables (aquellos con cardiopatías) y del personal sanitario, se han suspendido la mayoría de las consultas presenciales y se han puesto en marcha las consultas telemáticas. Este cambio se ha implementado en muy poco tiempo, pero parece que ha venido para quedarse. No obstante, hay grandes dudas sobre aspectos organizativos, legales, posibilidades de mejora, etc. En este documento de consenso de la Sociedad Española de Cardiología, tratamos de dar las claves para mejorar la calidad asistencial en nuestras nuevas consultas telemáticas, revisando las afecciones que el cardiólogo clínico atiende con más frecuencia en su consulta ambulatoria y proponiendo unos mínimos en ese proceso asistencial. Estas enfermedades son la cardiopatía isquémica, la insuficiencia cardiaca y las arritmias. En los 3 escenarios tratamos de clarificar los aspectos fundamentales que hay que revisar en la entrevista telefónica, a qué pacientes habrá que atender en una consulta presencial y cuáles serán los criterios para su seguimiento en atención primaria. El documento también recoge distintas mejoras que pueden introducirse en la consulta telemática para mejorar la asistencia de nuestros pacientes

The coronavirus disease 2019 (COVID-19) pandemic has changed how we view our consultations. To reduce the risk of spread in the most vulnerable patients (those with heart disease) and health personnel, most face-to-face consultations have been replaced by telemedicine consultations. Although this change has been rapidly introduced, it will most likely become a permanent feature of clinical practice. Nevertheless, there remain serious doubts about organizational and legal issues, as well as the possibilities for improvement etc. In this consensus document of the Spanish Society of Cardiology, we attempt to provide some keys to improve the quality of care in this new way of working, reviewing the most frequent heart diseases attended in the cardiology outpatient clinic and proposing some minimal conditions for this health care process. These heart diseases are ischemic heart disease, heart failure, and arrhythmias. In these 3 scenarios, we attempt to clarify the basic issues that must be checked during the telephone interview, describe the patients who should attend in person, and identify the criteria to refer patients for follow-up in primary care. This document also describes some improvements that can be introduced in telemedicine consultations to improve patient care

Telemedicine consultation for the clinical cardiologists in the era of COVID-19: present and future. Consensus document of the Spanish Society of Cardiology.

The coronavirus disease 2019 (COVID-19) pandemic has changed how we view our consultations. To reduce the risk of spread in the most vulnerable patients (those with heart disease) and health personnel, most face-to-face consultations have been replaced by telemedicine consultations. Although this change has been rapidly introduced, it will most likely become a permanent feature of clinical practice. Nevertheless, there remain serious doubts about organizational and legal issues, as well as the possibilities for improvement etc. In this consensus document of the Spanish Society of Cardiology, we attempt to provide some keys to improve the quality of care in this new way of working, reviewing the most frequent heart diseases attended in the cardiology outpatient clinic and proposing some minimal conditions for this health care process. These heart diseases are ischemic heart disease, heart failure, and arrhythmias. In these 3 scenarios, we attempt to clarify the basic issues that must be checked during the telephone interview, describe the patients who should attend in person, and identify the criteria to refer patients for follow-up in primary care. This document also describes some improvements that can be introduced in telemedicine consultations to improve patient care.

[Telemedicine consultation for the clinical cardiologists in the era of COVID-19: present and future. Consensus document of the Spanish Society of Cardiology]. / La consulta telemática para el cardiólogo clínico en tiempos de la COVID-19: presente y futuro. Documento de consenso de la Sociedad Española de Cardiología.

The coronavirus disease 2019 (COVID-19) pandemic has changed how we view our consultations. To reduce the risk of spread in the most vulnerable patients (those with heart disease) and health personnel, most face-to-face consultations have been replaced by telemedicine consultations. Although this change has been rapidly introduced, it will most likely become a permanent feature of clinical practice. Nevertheless, there remain serious doubts about organizational and legal issues, as well as the possibilities for improvement etc. In this consensus document of the Spanish Society of Cardiology, we attempt to provide some keys to improve the quality of care in this new way of working, reviewing the most frequent heart diseases attended in the cardiology outpatient clinic and proposing some minimal conditions for this health care process. These heart diseases are ischemic heart disease, heart failure, and arrhythmias. In these 3 scenarios, we attempt to clarify the basic issues that must be checked during the telephone interview, describe the patients who should attend in person, and identify the criteria to refer patients for follow-up in primary care. This document also describes some improvements that can be introduced in telemedicine consultations to improve patient care.

Impact of different models of improvement of continuity of care on lipid control and the delay of visits to cardiology.

Aims: To analyze the impact of implementing three different models of continuity of care on the delay of first visits to the cardiologist (management end point) and on LDL-cholesterol control rates among patients with atherosclerotic vascular disease (clinical end point). Methods: Observational, longitudinal and retrospective study of patients with cardiovascular disease and LDL-cholesterol ≥70 mg/dl attended in three hospitals (H1/H2/H3). In H1 and H2, a virtual system (telecardiology) was developed (in H1, internal audits and specific medical education were also performed). In H3 a cardiologist was integrated into the primary care center. Results: The delay of visits to cardiologist significantly improved from 66.5 ± 29.1 days to 34.1 ± 14.1 days (p < 0.001), as well as the intensification of lipid-lowering treatment and the achievement of lipid goals. LDL-cholesterol control rates were higher in H1 and the reduction of the delay of visits in H3. Conclusion: Continuity of care is associated with improvements in management and clinical end points.

Promoción de estilos de vida saludables: estrategias y escenarios / Promotion of healthy lifestyles: strategies and scenarios / Promoção de estilos de vida saudaveís: estrategias e cenarios

Resumen Objetivo: analizar las estrategias de promoción de la salud para el fomento de Estilos de Vida Saludables en escenarios de familia, trabajo, comunidad, educación y sector sanitario. Método: estudio descriptivo a partir de la revisión y análisis sistemático de estudios originales primarios sobre estrategias de promoción de la salud y estilos de vida saludables, haciendo uso de la lista de control PRISMA. Resultados: se identificaron tres estrategias de PS para el fomento de EVS, estas se basaron en información, educación, cambio de actitudes, fortalecimiento de la autoestima y toma de decisiones a través de salud móvil, técnicas de motivación, talleres prácticos y psicoeducación. Conclusiones: el desarrollo de estrategias que promueven estilos de vida saludables es incipiente en escenarios como el lugar de trabajo y la familia, lo cual genera una baja cobertura poblacional y demanda acciones interdisciplinarias desde diferentes campos como el de la Psicología de la Salud.

Abstract Objective: To analyze Health Promotion (HP) strategies for the encouragement of healthy lifestyles (EHL) in family, work, community, education and the health sector scenarios. Method: descriptive study based on the systematic review and analysis of primary original studies on health promotion strategies in healthy lifestyles, making use of the PRISMA checklist. Results: three HP strategies were identified for the promotion of EHL which were based on information, education, change of attitudes, strengthening of self-esteem and decision making through mobile health, motivation techniques, practical workshops and psychoeducation. Conclusions: the development of strategies that promote healthy lifestyles is incipient in scenarios such as the workplace and the family, which generates low population coverage and demands interdisciplinary actions from different fields such as the Psychology of health.

Resumo Objetivo: analisar as estratégias de promoção da saúde para o fomento de Estilos de Vida Saludáveis em cenários de família, trabalho, comunidade, educação e setor sanitário. Método: estudo descritivo a partir da revisão e analise sistemático de estudos originais primários sobre estratégias de promoção da saúde e estilos de vida saudáveis, fazendo uso da lista de controle PRISMA. Resultados: Identificaram-se três estratégias de PS para o fomento de EVS, estas se basearam em informação, educação, cambio de atitudes, fortalecimento da autoestima e toma de decisões a través de saúde móvel, técnicas de motivação, oficinas práticos e psico-educação. Conclusões: o desenvolvimento de estratégias que promovem estilos de vida saudáveis é incipiente em cenários como o lugar de trabalho e a família, o qual gera uma baixa cobertura populacional e demanda ações interdisciplinares desde diferentes campos como o da Psicologia da Saúde.

Molecular Interactions of Different Steroids Contributing to Sebum Production. Review.

Considerable progress has been made in learning about the physiology and biochemistry of the sebaceous glands and several of the diseases that affect this component of the skin. Of these diseases, acne has particular importance. It is associated with adolescence, and because of the hormonal changes that take place in this stage, when it is severe it can cause depression. Moreover, in a considerable proportion of acne sufferers both adolescent and adult, it can produce tumors and deformation of the sebaceous glands. This seriously affects the sufferers to the point where it may limit their professional activities because they do not want to be seen in public. Several important issues from classic studies on the sebaceous gland will be reviewed in this document to report the state of the art of current treatments for the pathology of these glands. The sebaceous gland is an intracrine organ, capable of synthesizing and metabolizing different steroidal hormones. The role of each of the enzymes involved in these processes of the skin will be analyzed. The presence of different hormone receptors in the scientific literature will be also reviewed, due to the role of the sebaceous gland in lipogenesis at different ages. We also describe the mechanism of action of androgens and progestins in relation to coregulators recruited for lipogenesis in this gland. We propose several new steroidal compounds based on their mechanism of action to block lipogenesis in the sebaceous glands. These molecules offer potential for new treatment options for skin diseases.

Activity of steroid 4 and derivatives 4a-4f as inhibitors of the enzyme 5α-reductase 1.

It is known that the growth of prostate metastatic bone tumor depends on androgens, and tumor formation can start from migratory malignant cells produced in that organ. These cells exhibit grater type 1 5α-reductase (5α-R1) activity than type 2 5α-reductase. Noteworthy, both isozymes convert testosterone (T) to the more active androgen dihydrotestosterone (DHT) in the target tissues. Thus, in order to potentially improve the prognosis of this disease, in this work, seven derivatives of 17-(1H-benzimidazol-1-yl)-16-formillandrosta-5,16-dien-3ß-yl benzoate (4a-f) and 17-(1H-benzimidazol-1-yl)-3-hydroxy-16-formylandrost-5,16-diene (4) were synthesized, characterized and identified as inhibitors of type 1 5α-reductase (5αR1). These derivatives having the advantage of improved plasma half-life. The inhibitory activity of the compounds towards 5α-R1 isoenzyme was determined by conversion of T into DHT in the presence or absence of compounds 4, 4a-f. Further, in vivo experiments were also carried out, treating gonadectomized hamsters with T and/or 4, 4a-f and evaluating their effect on the diameter of hamster flank organs and on the weight of the prostatic and seminal vesicles. Results indicated that compounds 4, 4b, 4c, served as in vitro inhibitors of the enzyme 5α-R1 and pharmacological experiments showed that 4 and derivatives 4a-f decreased the diameter of the flank glands, the weight of the prostate and seminal vesicles of treated hamsters without any appreciable toxicity during observation. Noteworthy the fact that compound 4 is the product, in all cases, of the hydrolysis of the series of esters 4a-f, thus they can serve as precursors (prodrugs) of the active form 4.

Selección de lo mejor del año 2017 en cardiología clínica. Continuidad asistencial entre cardiología y atención primaria / Selection of the best of 2017 in clinical cardiology. continuum healthcare between cardiology and primary care

No disponible

Selección de lo mejor del año 2017 en cardiología clínica. Novedades terapéuticas / Selection of the best of 2017 in clinical cardiology. Therapeutic novelties

No disponible

Synthesis of new derivatives of 21-imidazolyl-16-dehydropregnenolone as inhibitors of 5α-reductase 2 and with cytotoxic activity in cancer cells.

The aim of this study was to synthesize several 16-dehydropregnenolone derivatives containing an imidazole ring at C-21 and a different ester moiety at C-3 as inhibitors of 5α-reductase 1 and 2 isoenzymes. Their binding capacity to the androgen receptor (AR) was also studied. Additionally, we evaluated their pharmacological effect in a castrated hamster model and their cytotoxic activity on a panel of cancer cells (PC-3, MCF7, SK-LU-1). The results showed that only the derivatives with an alicyclic ester at C-3 showed 5α-R2 enzyme inhibition activity, the most potent of them being 21-(1H-imidazol-1-yl)-20-oxopregna-5,16-dien-3ß-yl-cyclohexanecarboxylate with an IC50 of 29nM. This is important because prostatic benign hyperplasia is directly associated with the presence of 5α-R2. However, all the derivatives failed to inhibit 5α-R1 or bind to the AR. These alicyclic ester derivatives decreased the weight and size of androgen-dependent glands in the hamster, indicating they are very active in vivo and are not toxic. In addition, the 21-(1H-imidazol-1-yl)-20-oxopregna-5,16-dien-3ß-yl-acetate derivative showed the highest cytotoxic activity on the three cancer cell lines studied. It is therefore important in the synthesis of steroidal compounds to consider the size of the ester moiety at C-3 of the steroid skeleton, which is key in obtaining biological activity, as observed in this experiment.

ABCC3 Polymorphisms and mRNA Expression Influence the Concentration of a Carboxylic Acid Metabolite in Patients on Clopidogrel and Aspirin Therapy.

Acetylsalicylic acid (ASA) and clopidogrel combined therapy has been reported to be beneficial in patients with acute coronary syndrome (ACS). Antiplatelet drug resistance, especially to clopidogrel, is a multifactorial phenomenon that affects a large number of ACS patients. The genetic contribution to this drug response is not fully elucidated. We investigated the relationship of ABC-type efflux subfamily C member 3 (ABCC3) polymorphisms and mRNA expression with plasma concentrations of clopidogrel, salicylic acid (SA) and a carboxylic acid metabolite (CAM). Clopidogrel, CAM and SA plasma concentrations were measured simultaneously by liquid chromatography-tandem mass spectrometry (LCMS/MS) from 83 ACS patients undergoing percutaneous coronary intervention. ABCC3 (rs757421, rs733392 and rs739923) and CYP2C19*2 (rs4244285) polymorphisms as well as mRNA expression were evaluated. A positive correlation was found between CAM concentrations and ABCC3 mRNA expression (r = 0.494, p < 0.0001). Patients carrying genotype AA (rs757421 variant) had higher CAM concentrations and ABCC3 mRNA expression as compared to those of GG + GA carriers (p = 0.017). A multiple linear regression analysis revealed that ABCC3 mRNA expression (p = 0.017), rs757421 AA genotype (p = 0.001), blood collection time (p = 0.018) and clopidogrel dose (p = 0.001) contributed to the concentration of CAM. No associations were observed for the CYP2C19*2 polymorphism. These results suggest that up-regulation of ABCC3 mRNA expression leads to increased plasma CAM levels through MRP3-mediated cell efflux. The ABCC3 rs757421 polymorphism may contribute to gene expression. Therefore, ABCC3 may be a potential biomarker for the response to clopidogrel.

ABCC3 Polymorphisms and mRNA Expression Influence the / Concentration of a Carboxylic Acid Metabolite in Patients on / Clopidogrel and Aspirin Therapy

Acetylsalicylic acid (ASA) and clopidogrel combined therapy has been reported to be beneficial in patients with acute coronary syndrome (ACS). Antiplatelet drug resistance, especially to clopidogrel, is a multifactorial phenomenon that affects a large number of ACS patients. The genetic contribution to this drug response is not fully elucidated. We investigated the relationship of ABC-type efflux subfamily C member 3 (ABCC3) polymorphisms and mRNA expression with plasma concentrations of clopidogrel, salicylic acid (SA) and a carboxylic acid metabolite (CAM). Clopidogrel, CAM and SA plasma concentrations were measured simultaneously by liquid chromatography-tandem mass spectrometry (LCMS/MS) from 83 ACS patients undergoing percutaneous coronary intervention. ABCC3 (rs757421, rs733392 and rs739923) and CYP2C19*2 (rs4244285) polymorphisms as well as mRNA expression were evaluated. A positive correlation was found between CAM concentrations and ABCC3 mRNA expression (r = 0.494, p < 0.0001). Patients carrying genotype AA (rs757421 variant) had higher CAM concentrations and ABCC3 mRNA expression as compared to those of GG + GA carriers (p = 0.017). A multiple linear regression analysis revealed that ABCC3 mRNA expression (p = 0.017), rs757421 AA genotype (p = 0.001), blood collection time (p = 0.018) and clopidogrel dose (p = 0.001) contributed to the concentration of CAM. No associations were observed for the CYP2C19*2 polymorphism. These results suggest that up-regulation of ABCC3 mRNA expression leads to increased plasma CAM levels through MRP3-mediated cell efflux. The ABCC3 rs757421 polymorphism may contribute to gene expression. Therefore, ABCC3 may be a potential biomarker for the response to clopidogrel.

ABCC3 Polymorphisms and mRNA expression influence the concentration of a carboxylic acid metabolite in patients on clopidogrel and aspirin therapy

Acetylsalicylic acid (ASA) and clopidogrel combined therapy has been reported to be beneficial in patients with acute coronary syndrome (ACS). Antiplatelet drug resistance, especially to clopidogrel, is a multifactorial phenomenon that affects a large number of ACS patients. The genetic contribution to this drug response is not fully elucidated. We investigated the relationship of ABC-type efflux subfamily C member 3 (ABCC3) polymorphisms and mRNA expression with plasma concentrations of clopidogrel, salicylic acid (SA) and a carboxylic acid metabolite (CAM). Clopidogrel, CAM and SA plasma concentrations were measured simultaneously by liquid chromatography-tandem mass spectrometry (LCMS/MS) from 83 ACS patients undergoing percutaneous coronary intervention. ABCC3 (rs757421, rs733392 and rs739923) and CYP2C19*2 (rs4244285) polymorphisms as well as mRNA expression were evaluated. A positive correlation was found between CAM concentrations and ABCC3 mRNA expression (r = 0.494, p < 0.0001). Patients carrying genotype AA (rs757421 variant) had higher CAM concentrations and ABCC3 mRNA expression as compared to those of GG + GA carriers (p = 0.017). A multiple linear regression analysis revealed that ABCC3 mRNA expression (p = 0.017), rs757421 AA genotype (p = 0.001), blood collection time (p = 0.018) and clopidogrel dose (p = 0.001) contributed to the concentration of CAM. No associations were observed for the CYP2C19*2 polymorphism...

Pharmacogenomics of anti-platelet therapy focused on peripheral blood cells of coronary arterial disease patients.

BACKGROUND: To investigate genes differentially expressed in peripheral blood cells (PBCs) from patients with coronary arterial disease (CAD) under double anti-platelet therapy. METHODS: Twenty-six CAD patients that were submitted to percutaneous coronary intervention (PCI) were selected to participate in this study. These patients took 100mg/day of acetylsalicylic acid (ASA) and 75mg/day of clopidogrel. Blood samples were collected before PCI to evaluate platelet reactivity using VerifyNow ASA and P2Y12 assays (Accumetrics). The patients were stratified into 4 quartiles based on ASA reaction units (ARUs) and P2Y12 reaction units (PRUs). Quartile 1 (Q1) patients were classified as responders and quartile 4 (Q4) patients as non-responders. Global mRNA expression from Q1 to Q4 was analyzed by microarray using the GeneChip Exon 1.0 ST array (Affymetrix) and was confirmed by RT-qPCR. RESULTS: Patients with ARU or PRU values within the first quartile (Q1, ARU<390 and PRU<151) were considered responders, while those who had ARU or PRU within the fourth quartile (Q4, ARU>467 and PRU>260) were considered nonresponders. The risk factors associated for CAD showed expected frequencies and no difference was found between Q1 and Q4. Microarray analysis identified 117 genes differentially expressed for ASA and 29 for clopidogrel between Q1 and Q4 groups (p<0.01, FC>1.2). CONCLUSION: The variation in response to ASA may be related with an increased expression of IGF1 and IGF1R, as well as a response to clopidogrel can be affected by pharmacokinetic change related to the reverse transport pathway by increased expression of ABCC3.