Cardiovascular Safety of Anagrelide in Healthy Subjects: Effects of Caffeine and Food Intake on Pharmacokinetics and Adverse Reactions

BACKGROUND: Essential thrombocythaemia (ET) is a rare clonal myeloproliferative disorder characterized by a sustained elevation in platelet count and megakaryocyte hyperplasia. Anagrelide is used in the treatment of ET, where it has been shown to reduce platelet count. Anagrelide is metabolized by cytochrome P450 (CYP) 1A2, and previous studies of the effect of food on the bioavailability and pharmacokinetics of anagrelide were conducted prior to the identification of the active metabolite, 3-hydroxyanagrelide. OBJECTIVES: The objectives of this study were to determine the effect of food and caffeine on the pharmacokinetics of anagrelide and its active metabolite, 3-hydroxyanagrelide, to monitor electrocardiogram (ECG) parameters following drug administration, and to document the relationship between palpitations, ECG changes and caffeine intake METHODS: Thirty-five healthy subjects who received 1 mg of anagrelide following either a 10-h fast or within 30 min of a standardized breakfast, including two cups of coffee, were studied. RESULTS: Time to maximum (peak) plasma concentration (C(max)) of anagrelide was 4.0 h in the fed and 1.5 h in the fasted group (p < 0.05); similar results were observed for 3-hydroxyanagrelide. The mean C(max) of anagrelide was 4.45 ± 2.32 ng/mL and 5.08 ± 2.99 ng/mL in the fed/caffeine and fasted groups, respectively; peak concentrations were higher for 3-hydroxyanagrelide in both the fed/caffeine and fasted groups. The most frequent adverse events (AEs) were headache (60 %) and palpitations (40 %). There were no serious AEs and all ECGs were normal, although significant reductions in PR interval, QRS length and QT interval were observed in both groups. Heart rate increased after anagrelide administration in both fed/caffeine and fasted states (p < 0.01); however, increased heart rate was significantly more frequent in the fed/caffeine state than in the fasted state (p < 0.001 for heart rate increase in the first hour after drug administration). There was a trend towards a greater heart rate increase in subjects reporting palpitations than in those without (mean heart rate ± SD at 1 h: 10.1 ± 6.4 vs. 8.0 ± 8.4 beats/min [p = 0.35]; at 4 h: 12.7 ± 7.5 vs. 9.1 ± 8.8 beats/min [p = 0.10], respectively). CONCLUSION: We conclude that food/caffeine delayed absorption of anagrelide. Anagrelide was generally well tolerated and had small effects on ECG parameters and heart rate. Caffeine may be implicated in a higher increase in heart rate and increased frequency of palpitations observed following administration of anagrelide with food/caffeine versus fasting

Cáncer y cardiotoxicidad en la población transgénero

La relación entre el diagnóstico de cáncer y enfermedades cardiovasculares es compleja, con pacientes recién diagnosticados enfrentando un mayor riesgo de enfermedad coronaria, insuficiencia cardíaca y fibrilación auricular. Comparados con la población general, tienen de dos a seis veces más riesgo de morir por causas cardiovasculares. Las complicaciones cardiovasculares derivadas de la quimioterapia y la radioterapia, junto con disparidades sociales y de acceso a la salud, complican la recopilación de datos precisos sobre la incidencia de cáncer y cardiotoxicidad en poblaciones marginadas. Entre la comunidad LGTBQ, ciertos tipos de cáncer son más frecuentes, y la administración de hormonas para la reafirmación de género también está bajo estudio. El retraso en el cribado de cáncer en la población transgénero resulta en detecciones tardías y muertes por cáncer. La investigación sobre cáncer en la población transgénero y cardiotoxicidad es limitada, pero se requiere atención especial para desarrollar estrategias de detección y prevención en situaciones específicas, como tumores dependientes de hormonas

New-onset atrial fibrillation and prognosis in nonagenarians after acute myocardial infarction

2.263 JCR (2013) Q2, 61/125 Cardiac & cardiovascular system

Cardiovascular Safety of Anagrelide in Healthy Subjects: Effects of Caffeine and Food Intake on Pharmacokinetics and Adverse Reactions

Essential thrombocythaemia (ET) is a rare clonal myeloproliferative disorder characterized by a sustained elevation in platelet count and megakaryocyte hyperplasia. Anagrelide is used in the treatment of ET, where it has been shown to reduce platelet count. Anagrelide is metabolized by cytochrome P450 (CYP) 1A2, and previous studies of the effect of food on the bioavailability and pharmacokinetics of anagrelide were conducted prior to the identification of the active metabolite, 3-hydroxyanagrelide.1.704 JCR (2013) Q3, 167/254 Pharmacology & pharmac

End-of-life care in a cardiology department: Have we improved?

nd-of-life care is not usually a priority in cardiology departments. We sought to evaluate the changes in end-of-life care after the introduction of a do-not-resuscitate (DNR) order protocol. Retrospective analysis of all deaths in a cardiology department in two periods, before and after the introduction of the protocol. Comparison of demographic characteristics, use of DNR orders, and end-of-life care issues between both periods, according to the presence in the second period of the new DNR sheet (Group A), a conventional DNR order (Group B) or the absence of any DNR order (Group C). The number of deaths was similar in both periods (n = 198 vs. n = 197). The rate of patients dying with a DNR order increased significantly (57.1% vs. 68.5%; P = 0.02). Only 4% of patients in both periods were aware of the decision taken about cardiopulmonary resuscitation. Patients in Group A received the DNR order one day earlier, and 24.5% received it within the first 24 h of admission (vs. 2.6% in the first period; P < 0.001). All patients in Group A with an implantable cardioverter defibrillator (ICD) had shock therapies deactivated (vs. 25.0% in the first period; P = 0.02). The introduction of a DNR order protocol may improve end-of-life care in cardiac patients by increasing the use and shortening the time of registration of DNR orders. It may also contribute to increase ICD deactivation in patients with these orders in place. However, the introduction of the sheet in late stages of the disease failed to improve patient participation.Sin financiación1.806 JCR (2016) Q3, 86/126 Cardiac and Cardiovascular Systems; Q4, 36/49 Geriatrics and GerontologyUE

Breast Radiotherapy-Related Cardiotoxicity. When, How, Why. Risk Prevention and Control Strategies

In recent decades, improvements in breast cancer management have increased overall patient survival; however, many cancer therapies have been linked to an important risk of cardiovascular adverse events. Cardio-oncology has been proposed as an emerging specialty to coordinate preventive strategies that improve the cardiovascular health of oncologic patients. It employs the most suitable personalized multidisciplinary management approach for each patient to optimize their cardiovascular health and improve their survival and quality of life. Radiotherapy is an essential part of the therapeutic regimen in breast cancer patients but can also increase the risk of cardiovascular disease. Therefore, minimizing the negative impact of radiation therapy is an important challenge for radiotherapy oncologists and cardiologists specializing in this field. The aim of the present review is to update our knowledge about radiation-induced cardiotoxicity in breast cancer patients by undertaking a critical review of the relevant literature to determine risk prevention and control strategies currently available.Sin financiación6.639 JCR (2020) Q1, 51/242 Oncology1.349 SJR (2021) Q1, 72/369 OncologyNo data IDR 2020UE

Oral anticoagulation in octogenarians with atrial fibrillation

Vitamin K antagonists (VKAs) are still largely employed, even in nonvalvular atrial fibrillation (AF). Our aim was to study the clinical profile of octogenarians treated with oral anticoagulation and to study the effect of age on the quality of VKAs anticoagulation. Data are from a prospective national registry in an adult Spanish population of nonvalvular AF. We included 1637 patients who had been receiving VKAs for at least 6 months before enrolment. Mean age was 73.8 ± 9.4 years. Patients aged > 80 years (N = 429) had a high risk profile with higher risk of stroke and bleeding than younger patients; CHA2DS2-VASc (Cardiac failure, Hypertension, Age > 74, Diabetes, Stroke, Vascular disease, Age 65–74 years, and Sex category) 4.5 ± 1.3 vs. 3.5 ± 1.6, p 64 years), Drugs/alcohol concomitantly) 2.4 ± 0.9 vs. 1.9 ± 1.1, p < 0.001. Creatinine clearance was lower in octogenarians than in younger patients (54.3 ± 16.1 ml/min vs. 69.5 ± 23.7 ml/min, p < 0.001) and severe renal disease with creatinine clearance < 30 ml/min was more frequent in octogenarians (5.2% vs. 2.2%, p < 0.001). In patients treated with VKAs (N = 1637), the international normalized ratio values of the 6 months previous to enrollment were similar in all age quartiles, as was the time in the therapeutic range. In this large registry octogenarians with nonvalvular AF had high risk of stroke and bleeding and frequent renal disease. VKAs anticoagulation quality was similar in octogenarians and in younger patients.Sin financiación6.189 JCR (2016) Q1, 16/126 Cardiac and Cardiovascular SystemsUE

Toward a Better Understanding of Cardiovascular Risk in the Transgender and Gender-Diverse Community: A Global Call to Action

On World Heart Day 2022, the Mexican Society of Cardiology, the Inter-American Society of Cardiology, and the World Heart Federation collaborated on a public call to action regarding the increased risk of adverse cardiovascular health outcomes in transgender and gender diverse (TGD) individuals. The aim of this article is to unpack the numerous factors that contribute to this, such as the social stigma faced by members of the TGD community, their reduced access to clinical care, and the scarcity of research regarding the unique needs of their community, which makes it difficult for clinicians to provide individualized medical care. Decreasing the incidence of adverse cardiovascular events among TGD individuals requires interventions such as educational reform in the medical community, an increase in inclusive research studies, and broader social initiatives intended to reduce the stigma faced by TGD individuals

El camino hacia una mejor comprensión del riesgo cardiovascular en la comunidad transgénero y diferentes géneros: un suplemento a la Declaración de Tijuana

En el Día Mundial del Corazón 2022, la Sociedad Mexicana de Cardiología, la Sociedad Interamericana de Cardiología y la Federación Mundial del Corazón colaboraron en una comunicación sobre el aumento del riesgo de resultados adversos para la salud cardiovascular en individuos transgénero y de género diverso (TGD). Este documento, conocido como la Declaración de Tijuana, instó a la comunidad cardiovascular global a trabajar en la comprensión y mitigación de este problema. Este artículo tiene como objetivo desentrañar los numerosos factores que lo provocan. Un ejemplo es el estigma social enfrentado por los miembros de la comunidad TGD, lo que conduce a un aumento del estrés y el riesgo de complicaciones cardiovasculares. Los pacientes TGD también tienen más probabilidades de tener un acceso insuficiente a la atención médica, y aquellos que la reciben a menudo se enfrentan a proveedores que no están adecuadamente educados sobre las necesidades únicas de su comunidad. Finalmente, hay evidencia que sugiere que las terapias hormonales de afirmación de género tienen un impacto en la salud cardiovascular, pero los estudios sobre este tema a menudo tienen preocupaciones metodológicas y hallazgos contradictorios. Disminuir la incidencia de eventos cardiovasculares adversos en esta comunidad requiere intervenciones como la reforma educativa en la comunidad médica, un aumento en los estudios de investigación sobre este tema e iniciativas sociales más amplias destinadas a reducir el estigma enfrentado por los individuos TGD

Guía mexicana de práctica clínica para el diagnóstico y el tratamiento de la insuficiencia cardiaca

La insuficiencia cardiaca crónica sigue siendo unas de las principales causas de afectación en el funcionamiento y en la calidad de vida de las personas que la presentan, así como una de las primeras causas de mortalidad en nuestro país y en todo el mundo. México tiene una alta prevalencia de factores de riesgo para desarrollar insuficiencia cardiaca, tales como hipertensión arterial, diabetes y obesidad, lo que hace imprescindible contar con un documento basado en la evidencia que brinde recomendaciones a los profesionales de la salud involucrados en el diagnóstico y el tratamiento de estos pacientes. Este documento establece la guía de práctica clínica (GPC) elaborada por iniciativa de la Sociedad Mexicana de Cardiología (SMC) en colaboración con la Agencia Iberoamericana de Desarrollo y Evaluación de Tecnologías en Salud, con la finalidad de establecer recomendaciones basadas en la mejor evidencia disponible y consensuadas por un grupo interdisciplinario y multicolaborativo de expertos. Cumple con estándares internacionales de calidad, como los descritos por el Institute of Medicine de los Estados Unidos de América (IOM), el National Institute of Clinical Excellence (NICE) del Reino Unido, la Intercollegiate Network for Scottish Guideline Development (SIGN) de Escocia y la Guidelines International Network (G-I-N). El grupo de desarrollo de la guía se integró de manera interdisciplinaria con el apoyo de metodólogos con experiencia en revisiones sistemáticas de la literatura y en el desarrollo de GPC. Se llevó a cabo y se condujo metodología de panel Delphi modificado para lograr un nivel de consenso adecuado en cada una de las recomendaciones contenidas en esta GPC. Esperamos que este documento contribuya para la mejor toma de decisiones clínicas y se convierta en un punto de referencia para los clínicos que manejan pacientes con insuficiencia cardiaca crónica en todas sus etapas clínicas, y de esta manera logremos mejorar la calidad en la atención clínica, aumentar la calidad de vida de los pacientes y disminuir las complicaciones de la enfermedad