The angiotensin II receptors type 1 and 2 modulate astrocytes and their crosstalk with microglia and neurons in an in vitro model of ischemic stroke.

BACKGROUND: Astrocytes are the most abundant cell type of the central nervous system and are fundamentally involved in homeostasis, neuroprotection, and synaptic plasticity. This regulatory function of astrocytes on their neighboring cells in the healthy brain is subject of current research. In the ischemic brain we assume disease specific differences in astrocytic acting. The renin-angiotensin-aldosterone system regulates arterial blood pressure through endothelial cells and perivascular musculature. Moreover, astrocytes express angiotensin II type 1 and 2 receptors. However, their role in astrocytic function has not yet been fully elucidated. We hypothesized that the angiotensin II receptors impact astrocyte function as revealed in an in vitro system mimicking cerebral ischemia. Astrocytes derived from neonatal wistar rats were exposed to telmisartan (angiotensin II type 1 receptor-blocker) or PD123319 (angiotensin II type 2 receptor-blocker) under normal conditions (control) or deprivation from oxygen and glucose. Conditioned medium (CM) of astrocytes was harvested to elucidate astrocyte-mediated indirect effects on microglia and cortical neurons. RESULT: The blockade of angiotensin II type 1 receptor by telmisartan increased the survival of astrocytes during ischemic conditions in vitro without affecting their proliferation rate or disturbing their expression of S100A10, a marker of activation. The inhibition of the angiotensin II type 2 receptor pathway by PD123319 resulted in both increased expression of S100A10 and proliferation rate. The CM of telmisartan-treated astrocytes reduced the expression of pro-inflammatory mediators with simultaneous increase of anti-inflammatory markers in microglia. Increased neuronal activity was observed after treatment of neurons with CM of telmisartan- as well as PD123319-stimulated astrocytes. CONCLUSION: Data show that angiotensin II receptors have functional relevance for astrocytes that differs in healthy and ischemic conditions and effects surrounding microglia and neuronal activity via secretory signals. Above that, this work emphasizes the strong interference of the different cells in the CNS and that targeting astrocytes might serve as a therapeutic strategy to influence the acting of glia-neuronal network in de- and regenerative context.

Recomendación rápida sobre el uso de antihipertensivos IECA/ARA II en pacientes con riesgo o documentación de COVID-19 / Rapid recommendation on the use of ACEI/ARA antihypertensives in patients at risk or with documented COVID-19

Ciertos hallazgos preclínicos generaron preocupación en la comunidad científica y en la población general sobre el uso de inhibidores de la enzima convertidora de angiotensina (IECA) y los antagonistas del receptor de la angiotensina II (ARAII), y los posibles desenlaces adversos asociados con relación a la infección por el nuevo Coronavirus (SARS-Cov-2).Por este motivo, nos planteamos como objetivo proveer de recomendaciones dinámicas (living recommendations) para el tratamiento con fármacos IECA o ARA II en pacientes con riesgo o documentación de infección por SARS-CoV-2 (en todo su espectro de gravedad). Se utilizó como metodología la adaptación/adopción de guías de práctica clínica bajo el enfoque GRADE, actualizando la evidencia al 7 de abril de 2020 mediante búsquedas en múltiples bases de datos y consultando a un panel multidisciplinario libre de conflictos de interés. Como resultado de este proceso se arribó a la siguiente afirmación: se recomienda, en contexto de la pandemia de COVID-19, en personas que se encuentran en tratamiento con IECA/ARAII, mantener el tratamiento sin cambios por sobre suspenderlo o reemplazarlo por otros fármacos (Recomendación fuerte a favor - calidad de evidencia baja). (AU)

Certain preclinical findings raised concerns in the scientific community and in the general population about the use ofangiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor antagonists (ARA) and the possible adverse outcomes associated with the infection with the new Coronavirus (SARS-Cov-2). For this reason, our objective is to provide living recommendations for treatment with ACEI or ARA in patients with risk or documentation of SARS-CoV-2 infection (inall its severity spectrum). The adaptation/adoption of clinical practice guidelines under the GRADE approach was used as a methodology, updating the evidence as of April 7, 2020, by searching multiple databases and consulting a multidisciplinary panel free of conflicts of interest. As a result of this process, the following statement was reached: it is recommended, in the context of the COVID-19 pandemic, in people who are undergoing treatment with ACEI/ARA, to maintain the treatment unchanged instead of its suspension or replacement with other drugs (Strong recommendation in favor - low quality ofevidence). (AU)

Supresión de angiotensia II en la infección por el virus SARS-CoV-2: una propuesta terapeútica / Angiotensin II suppression in SARS-CoV-2 infection: a therapeutic approach

No disponible

Tratamiento farmacológico inicial del paciente con insuficiencia cardíaca con función sistólica reducida: ¿es importante el orden de inicio y las dosis conseguidas? / Initial pharmacological treatment of the patient with heart failure with reduced systolic function: is the order of the initial and subsequent doses important?

No disponible

Hepatitis colestásica por candesartán: descripción de un caso / No disponible

No disponible

Estatinas en COVID-19: ¿existe algún fundamento? / Statins in COVID-19: is there any foundation?

El coronavirus tipo 2 del síndrome respiratorio agudo grave (SARS-CoV-2) es el agente causal de la enfermedad por coronavirus 2019 (COVID-19). El síndrome de distress respiratorio agudo constituye la principal causa de muerte por COVID-19 y ocurre por una respuesta inflamatoria exagerada que provoca la liberación de citocinas proinflamatorias como interleucinas y factor de necrosis tumoral alfa (TNF-α). Las estatinas son fármacos hipolipemiantes con efectos pleiotrópicos. Han demostrado beneficio en el manejo de enfermedades inflamatorias y autoinmunes como el lupus eritematoso sistémico, la artritis reumatoide y la esclerosis múltiple. Además, debido a sus propiedades inmunomoduladoras se han utilizado en el tratamiento de diversas enfermedades infecciosas como neumonía adquirida en la comunidad e influenza. En esta revisión analizamos los fundamentos fisiopatológicos que apoyan el uso de estatinas como tratamiento coadyuvante en pacientes con COVID-19

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causal agent of coronavirus disease 2019 (COVID-19). Acute respiratory distress syndrome is the main cause of death from COVID-19 and occurs due to an exaggerated inflammatory response that causes the release of pro-inflammatory cytokines such as interleukins and tumor necrosis factor-alpha (TNF-α). Statins are lipid lowering drugs with pleiotropic effects. They have shown benefit in the management of inflammatory and autoimmune diseases such as systemic lupus erythematosus, rheumatoid arthritis and multiple sclerosis. Furthermore, due to their immunomodulatory properties, they have been used in the treatment of various infectious diseases such as community-acquired pneumonia and influenza. In this review we analyze the pathophysiological foundations that support the use of statins as an adjunctive treatment in patients with COVID-19

Evaluación de la utilización de los antagonistas de los receptores de la angiotensina II en hipertensión arterial / Assessment of the utilization of angiotensin receptor blockers in hypertension

OBJETIVO: Evaluar en nuestra Área de Salud el grado en que la utilización de antagonistas de los receptores de la angiotensina II (ARA-II) se ajusta a los criterios propuestos por la Comunidad Autónoma de Madrid (CAM) antes de la instauración del "Plan de Actuación de ARA-II". Estudiar las indicaciones para las que se prescriben e identificar aquellos factores que han podido influir en su prescripción. MÉTODOS: Estudio de utilización de medicamentos del tipo indicación-prescripción, descriptivo y transversal, en el que se seleccionaron pacientes con hipertensión arterial y en tratamiento con ARA-II ingresados en un Hospital General Universitario durante un periodo de estudio de 3 meses. De acuerdo con las situaciones clínicas recogidas en el Documento de la CAM "Criterios para establecer el lugar en la terapéutica de los antagonistas de los receptores de la angiotensina II", se calculó el porcentaje de pacientes con "prescripción adecuada" y "prescripción no adecuada" de ARA-II y se analizó si la edad y el sexo tenían influencia en el tipo de prescripción o en las principales indicaciones para las que se prescribieron. RESULTADOS: De los 153 pacientes que se incluyeron en el estudio, el 67,3% tuvieron una "prescripción no adecuada", el 47,6% de ellos por prescripción de ARA-II como primer fármaco antagonista del sistema renina angiotensina aldosterona y el 34,0% por mal control de la tensión arterial con inhibidores de la enzima convertidora de angiotensina (IECA). No se encontraron diferencias estadísticamente significativas por edad o sexo en cuanto al tipo de prescripción o en las principales indicaciones para las que se prescribieron. CONCLUSIONES: La adecuación a los criterios de uso del Documento de ARA-II se produjo en el 32,7% de los casos. Además, no se observó que factores como la edad y el sexo influyeran en el tipo de prescripción. Asimismo, se evidenciaron percepciones erróneas en el concepto de superioridad de los fármacos ARA-II frente a los IECA

OBJECTIVE: To assess the degree in which the utilization of angiotensin receptor blockers (ARBs) in our Healthcare Area fits the criteria proposed by the Autonomous Community of Madrid (CAM) before setting "Plan de Actuación de ARA-II" ("Action Plan ARA-II"). To study the indications for which are prescribed and to identify those factors that can show influence in prescription. METHODS: Drug utilization study of the type indication-prescription, descriptive and transversal, for which ARBs-treated and hypertensive patients admitted to a University General Hospital for a study period of 3 months were selected. Based on the clinical situations summarized in the CAM Document "Criterios para establecer el lugar en la terapéutica de los antagonistas de los receptores de la angiotensina II" ("Criteria for the place of angiotensin receptor blockers in the therapeutic"), a percentage of patients with "appropriate prescription" and "inadequate prescription" of ARBs was calculated and analyzed in order to determine if the age and the sex were related to the type of prescription or the main indications for which they had been prescribed. RESULTS: Out of the 153 patients included in the study, 67.3% had a "inadequate prescription", 47.6% of them due to an ARBs prescription as the first drug inhibitor of the renin-angiotensin-aldosterone system and 34.0% owing to a poor control of blood pressure with angiotensin-converting enzyme inhibitors (ACEi). There were no statistically significant differences found either by age or sex in the type of prescription or in the main indications for which they were prescribed. CONCLUSIONS: The adequacy of the criteria for the utilisation of ARBs Document occurred in 32.7% of cases. In addition, factors such as age and sex did not seem to affect the type of prescription. Misconceptions of superiority of ARBs versus ACEi were evidenced as well

Influence of PD 123319 (AT2-Receptor Antagonist) on Catecholamine Secretion in the Perfused Rat Adrenal Medulla

BACKGROUND: The aim of this study was to examine whether PD 123319 (an angiotensin II type 2 [AT2] receptor antagonist) can influence the release of catecholamines (CA) from the perfused model of the rat adrenal medulla. METHODS: The adrenal gland was isolated by the modification of Wakade method, and perfused with normal Krebs-bicarbonate solution. The content of CA was measured using the fluorospectrophotometer. RESULTS: During perfusion of PD 123319 (range, 5 to 50 nM) into an adrenal vein for 90 minutes the CA secretory responses evoked by acetylcholine (ACh), high K+, 1,1-dimethyl-4-phenylpiperazinium iodide (DMPP), and McN-A-343 was dose- and time-dependently inhibited. Furthermore, loading with PD 123319 for 90 minutes also markedly inhibited the CA secretory responses evoked by 4-dihydro-2,6-dimethyl-3-nitro-4-(2-trifluoro-methyl-phenyl)-pyridine-5-carboxylate (Bay-K-8644), cyclopiazonic acid, veratridine, and angiotensin II (Ang II). PD 123319 did not affect basal CA output. Simultaneous perfusion of PD 123319 and CGP 42112 perfused into an adrenal vein for 90 minutes rather more potently inhibited the CA seretory responses evoked by Ach, high K+, DMPP, Bay-K-8644, veratridine, and Ang II compared to the inhibitory effect by PD123319-treated alone. CONCLUSIONS: Taken together, these results show that PD 123319 inhibits the CA secretion evoked by both cholinergic and Ang II receptor stimulation from the perfused rat adrenal medulla. This inhibitory effect of PD 123319 seems to be exerted by blocking the influx of both Na+ and Ca2+ through their voltage-dependent channels into the rat adrenomedullary chromaffin cells as well as by reducing the Ca2+ release from its cytoplasmic calcium store, which may be relevant to AT2 receptor blockade. Based on these present data, it is thought that PD 123319 has different activity from previously known AT2 antagonist activity in the perfused adrenal medulla, and that AT2 receptors may be involved in the rat adrenomedullary CA secretion.

The effect of angiotensin II on phosphoinositide-3 kinase/Akt cascade in cultured fibroblasts derived from patients with hypertrophic scars / 中华整形外科杂志

<p><b>OBJECTIVE</b>To study the effect of angiotensin II on phosphoinositide-3 kinase/Akt cascade in cultured fibroblasts derived from patients with hypertrophic scars.</p><p><b>METHODS</b>The expression of AT1 and AT2 receptor was detected by immunofluorescence staining. Cultured human skin fibroblasts were treated with Ang II (10(-9) - 10(-7) mol/L), with or without an AT1 receptor blocker, valsartan or an AT2 receptor antagonist, PD123319. The phosphorylation of Akt was detected by western blotting, and PI3K activity was measured by Assay of PI3-K activity.</p><p><b>RESULTS</b>Immunofluorescence staining showed that cultured fibroblasts derived from hypertrophic scars expressed both AT1 and AT2 receptors. Ang II increased Akt phosphorylation and PI3K activity in cultured hypertrophic scar fibroblasts in a dose- and time-dependent manner. Additionally, Ang II-induced Akt phosphorylation was blocked by wortmannin, a PI3-K inhibitor. This Ang II-activated PI3-K/Akt cascade was significantly inhibited by valsartan, an AT1 receptor specific blocker (P<0.05), whereas enhanced by PD123319, an AT2 receptor antagonist (P<0.05).</p><p><b>CONCLUSION</b>These results indicate that Ang II receptors regulates PI3-K/Akt cascade of hypertrophic scars fibroblasts via AT1 and AT2.</p>

Olmesartán: evidencia y práctica clínica / Olmesartan: evidence and clinical practice

Olmesartán medoxomilo es un antagonista no peptídico del receptor AT1 de la angiotensina con afinidad superior a la de otros fármacos del grupo. Ha demostrado en numerosos ensayos clínicos su eficacia antihipertensiva y su buena tolerabilidad. Se ha comparado en ensayos clínicos con otros fármacos del grupo (azilsartán, candesartán, irbesartán, losartán y valsartán). En general, el efecto de olmesartán administrado por vía oral, una sola vez al día a dosis de entre 20 y 40 mg, ha sido superior en cuanto a la reducción de cifras tensionales, se ha iniciado antes y ha persistido durante 24 h. Varios metaanálisis han confirmado estas ventajas de olmesartán. Hay algunos estudios que demuestran propiedades organoprotectoras, en especial de restauración de la función endotelial. El patrón y la frecuencia de las reacciones adversas son comparables a los del placebo. Como consecuencia de sus propiedades farmacodinámicas y farmacocinéticas, olmesartán puede presentar ventajas sobre otros fármacos antagonistas del receptor de la angiotensina en el tratamiento de la hipertensión arterial (AU)

Olmesartan medoxomil is a nonpeptide angiotensin II-type I receptor (AT1) antagonist with greater affi nity for this receptor than other drugs in this class. Several clinical trials have demonstrated its effi cacy in lowering blood pressure and its good tolerability. This drug has been compared in clinical trials with other drugs in the same class (azilsartan, candesartan, irbesartan, losartan and valsartan). In general, olmesartan administered orally at a dose of between 20 and 40 mg has provided superior effi cacy in lowering blood pressure; this effect is initiated earlier than with other drugs and persists for 24 hours. The advantages of olmesartan have been confi rmed by several meta-analyses. Some studies show organ protective properties, especially in restoring endothelial function. The pattern and frequency of adverse reactions are similar to those of placebo. As a result of its pharmacodynamic and pharmacokinetic properties, olmesartan could offer advantages over other angiotensin receptor antagonists in the treatment of hypertension (AU)

Aspectos prácticos de la combinación de 3 fármacos antihipertensivos a dosis fijas / Practical features of triple-antihypertensive fixed-dose drug combinations

Recientes estudios realizados en España demuestran un incremento en el grado de control de la hipertensión arterial (HTA) asociado a una mayor utilización de la terapia combinada. La combinación de fármacos antihipertensivos, como señalan todos los ensayos clínicos de morbimortalidad, es una condición fundamental para lograr los objetivos de control tensional y reducir las complicaciones cardiovasculares asociadas a la HTA. Sin embargo, en la práctica clínica todavía queda un largo recorrido hasta alcanzar unos niveles de control aceptables. Dos de las barreras más ampliamente reconocidas son el incumplimiento terapéutico por parte del paciente y la actitud conservadora de algunos médicos (inercia). Las combinaciones de 3 fármacos a dosis fijas pueden ayudar a vencer dichas barreras, entre otras razones, por la simplificación del tratamiento que comporta su uso. Algunos estudios, entre los que destaca el TRINITY, demuestran que una combinación de olmesartán, amlodipino e hidroclorotiazida puede conseguir tasas de control de hasta el 80%. Además, en relación con la tolerabilidad de las combinaciones triples actualmente disponibles en España, tiene la ventaja, al incluir un antagonista de los receptores de la angiotensina II (ARA II) en su composición, de reducir la incidencia de efectos adversos clínicos (edema periférico de los antagonistas del calcio) y metabólicos (hipopotasemia de las tiazidas). Los posibles candidatos a recibir una triple combinación fija son los pacientes no controlados con 2 fármacos o aquellos con cifras de presión arterial en objetivo tratados con 3 fármacos, con una combinación fija de 2 y 1 en asociación libre (AU)

Recent studies performed in Spain show an increase in hypertension (HT) control associated with greater use of combination therapy. As indicated by all clinical trials analyzing morbidity and mortality, antihypertensive combinations are essential to achieve blood pressure targets and reduce the cardiovascular complications of HT. However, in clinical practice, blood pressure values are still far from acceptable. Two of the most widely recognized barriers to acceptable control are lack of patient adherence and the conservative attitudes of some physicians (inertia). Triple-drug fixed-dose combinations for the treatment of HT can help to overcome these barriers as, among other reasons, these regimens simplify the treatment. Some studies, notably the TRINITY trial, have shown that the combination of olmesartan, amlopidine and hydrochlorothiazide can achieve blood pressure control rates of 80%. Moreover, by including angiotensin II receptor antagonists, the triple combinations currently available in Spain have the advantage of reducing the incidence of clinical adverse effects (the peripheral edema associated with calcium channel blockers) and metabolic adverse effects (thiazide hypokalemia), thus increasing tolerability. Possible candidates for receiving fixed-dose triple-drug combination therapy are patients poorly controlled with two drugs or those with blood pressure values on target receiving triple therapy, with a fixed combination of two and a free combination of a third (AU)

Selección de olmesartán en monoterapia, combinación o triple terapia en función del descenso necesario de la presión arterial / Selection of mono-, combination or triple therapy with olmesartan according to target decrease in blood pressure

Para minimizar el riesgo cardiovascular derivado de la hipertensión arterial (HTA) es de vital importancia alcanzar los objetivos terapéuticos, idealmente en el menor tiempo posible. La capacidad hipotensora de los diferentes fármacos está bien determinada por los diferentes estudios que avalan su uso. Por ello, el clínico debería elegir el tratamiento con criterio basándose en el descenso de presión arterial que requiera el paciente y utilizar un fármaco o combinación cuya potencia antihipertensiva permita prever que se logre el objetivo terapéutico. Olmesartán es un antagonista de los receptores de la angiotensina II (ARA II) de notable potencia hipotensora, bien tolerado y cuya combinación con dihidropiridinas y/o hidroclorotiazidas se halla bien establecida. En este artículo se revisan las evidencias que justifican el uso de olmesartán o sus combinaciones en el contexto actual del manejo de la HTA. Se presta especial atención en determinar la potencia hipotensora demostrada del fármaco para precisar los casos en los que es esperable alcanzar los objetivos terapéuticos, su comparación con otros fármacos de uso común, las evidencias en el control de la presión arterial durante las 24 h y la eficacia de las combinaciones terapéuticas (AU)

Achieving therapeutic targets is essential to reduce the cardiovascular risk of hypertension, ideally in as short a time as possible. The hypotensive effectiveness of the distinct drugs has been well characterized by the various studies supporting their use. Therefore, clinicians should base their selection of the drug to be used on the target blood pressure decrease required in each patient and prescribe a drug or drug combination with sufficient antihypertensive potency to achieve the desired reduction. Olmesartan is an angiotensin II receptor antagonist with marked hypotensive potency that is well tolerated and whose use in combination with dihydropyridines and/or hydrochlorothiazide has been well established. The present article reviews the evidence supporting the use of olmesartan as monotherapy or in combination treatment in the current context of the management of hypertension. Special attention is paid to determining the demonstrated blood pressure-lowering potency of this drug in situations in which the therapeutic targets can realistically be achieved; we compare this agent with other commonly used drugs and discuss the evidence on 24-hour blood pressure control, as well as the effectiveness of therapeutic combinations (AU)

Farmacoeconomía de olmesartán en combinaciones a dosis fijas para el tratamiento de la hipertensión arterial / Pharmacoeconomics of fixed-dose combinations with olmesartan in the treatment of hypertension

La hipertensión arterial constituye uno de los principales factores de riesgo por su elevada prevalencia y riesgo de complicaciones. Se ha progresado en la inercia clínica de la enfermedad, aunque el control de la presión arterial sigue siendo mejorable en colectivos específicos. La farmacoeconomía es una aplicación de la economía de la salud que nos permite conocer cuál es la eficiencia de las diferentes alternativas terapéuticas utilizables para tratar la hipertensión. Los antagonistas de los receptores de la angiotensina II (ARA II) han demostrado ser fármacos antihipertensivos efectivos y seguros, aunque la comparación entre los diferentes ARA II presenta resultados contradictorios. Olmesartán medoxomilo es un fármaco eficaz y bien tolerado, similar o ligeramente más eficaz que otros ARA II, tanto en monoterapia como en combinación fija (doble o triple). La hipertensión arterial no diagnosticada o no tratada es la principal causa de disminución de la efectividad y eficiencia en situación de práctica clínica habitual; su tratamiento requiere desarrollar estrategias basadas en análisis de coste-eficiencia, para reducir los costes sanitarios y maximizar los resultados. Los escasos estudios publicados sugieren que olmesartán en monoterapia, en comparación con otros ARA II, reduce de forma similar o superior el riesgo cardiovascular y las complicaciones a un menor coste. La terapia combinada con 2 o 3 antihipertensivos también parece tener un perfil de costeefectividad favorable, a pesar de que el coste del tratamiento es mayor. Cabe destacar la escasez de datos de coste-efectividad sobre el uso de dosis fijas de ARA II en general y de olmesartán en particular en terapias de combinación (AU)

Hypertension is a major risk factor due to its high prevalence and the risk of complications. Clinical inertia has been reduced, although blood pressure control could still be improved in certain specific groups. Pharmacoeconomics is an application of health economics that can be used to determine the efficiency of the various therapeutic alternatives available to treat hypertension. Angiotensin II receptor antagonists (ARA II) have been shown to be safe and effective hypotensive drugs, although comparisons among the distinct ARA II have yielded contradictory results. Olmesartan medoxomil is an effective and well tolerated drug with similar or slightly superior efficacy to other ARA II, both in monotherapy and in fixed-dose double- or triple-combination therapy. Undiagnosed or untreated hypertension is the main cause of reduced effectiveness and efficiency in routine clinical practice; treatment requires the development of strategies based on cost-efficiency analyses to reduce health costs and optimize results. The few published studies suggest that olmesartan monotherapy produces a similar or greater reduction in cardiovascular risk and complications than other ARA II and at a lower cost. Combination therapy with two or three antihypertensive agents also seems to have a favorable cost-effectiveness profile, even though the cost of treatment is higher. Importantly, in combination therapies, there is a scarcity of cost-effectiveness data on the use of fixed-doses of ARA II in general and of olmesartan in particular (AU)

Antagonistas de los receptores de la angiotensina II en el tratamiento de la hipertensión arterial, las enfermedades cardiovasculares y las renales. Realidad y futuro / No disponible

Los antagonistas de los receptores de angiotensina II (ARA II) y los inhibidores de la enzima de conversión de la angiotensina (IECA) son las 2 clases terapéuticas más utilizadas en el tratamiento de la hipertensión arterial, y en la prevención y tratamiento de las enfermedades cardiovascular y renal. Los estudios con ARA II han demostrado una replicación de los beneficios obtenidos anteriormente en los estudios con IECA, al igual que una efectividad preventiva similar en los estudios de comparación directa. En otros estudios comparativos frente a otras estrategias terapéuticas han demostrado prevenir la enfermedad cardiovascular en todos sus estadios evolutivos, así como una superioridad frente a otros fármacos en la prevención primaria y secundaria del ictus. Añadido a esta efectividad terapéutica, los ARA II son la clase terapéutica cardiovascular asociada a una mejor tolerabilidad. Este fenómeno se traduce en una mayor adherencia al tratamiento prescrito, así como en su mayor persistencia. Todo parece indicar que, a largo plazo, este hecho se traduce en la mejor protección posible frente a la enfermedad cardiovascular. Asimismo, todo apunta a que tanto los IECA como los ARA II contienen fármacos de largo recorrido en el tratamiento de varias generaciones y deberán convivir en indicaciones similares. Salvo que aparezcan nuevos datos en el futuro, a igualdad de efectividad, la mejor tolerabilidad de los ARA II los posiciona como la forma preferente del bloqueo del sistema renina-angiotensina en el tratamiento de enfermedades crónicas asintomáticas, como la hipertensión arterial (AU)

Angiotensin receptor antagonists (ARB) and angiotensin converting-enzyme (ACE) inhibitors are the two most widely used drug classes in the treatment of hypertension and in the prevention and treatment of cardiovascular and renal diseases. Studies with ARB have been able to replicate the benefits previously obtained in studies with ACE inhibitors, while direct-comparison studies have shown the two drugs to have a similar preventive efficacy. Other studies comparing ARB with other therapeutic strategies have shown these drugs to prevent cardiovascular disease at all stages of its development and progression and to be superior to other drugs in the primary and secondary prevention of stroke. In addition to this therapeutic efficacy, ARB are the cardiovascular drug class associated with the most favorable tolerability, leading to greater treatment adherence and persistence. All the evidence seems to indicate that, in the long term, this phenomenon possibly improves protection against cardiovascular disease. Likewise, the evidence also indicates that both ACE inhibitors and ARB are drug classes that include agents with a long future in the treatment of several generations and that they will probably be used in similar indications. Unless new data appear in the future, given the equal effectiveness of both drug classes, the better tolerability of ARB places them in a preferential position as renin-angiotensin system blockers in the treatment of chronic asymptomatic diseases such as hypertension (AU)

Olmesartán con diuréticos o con antagonistas del calcio: ¿a qué perfil de paciente hipertenso? / Calcium channel blockers or diuretics as an add-on to olmesartan in hypertension: indication according to patient profile

La combinación de olmesartán, tanto con diurético tiazídico como con amlodipino, ha demostrado un efecto antihipertensivo adicional, con buena tolerabilidad y una menor aparición de efectos secundarios. Hay pocos estudios que hayan evaluado las diferencias entre esquemas terapéuticos que incluyan olmesartán en asociación con diuréticos o con amlodipino. Dichas diferencias dependerán, fundamentalmente, de los efectos no relacionados con el descenso de la presión arterial (PA) de los fármacos que acompañan a olmesartán, ya que ambas combinaciones son similares en cuanto a eficacia antihipertensiva. En este artículo se revisan los efectos de ambas combinaciones en diferentes situaciones clínicas, como el riesgo metabólico del paciente hipertenso, su edad, la variabilidad de la PA o de la PA central (AU)

The combination of olmesartan both with a thiazide diuretic or with amlodipine has been shown to confer an additional blood pressure-lowering effect, with good tolerability and fewer adverse effects. Few studies have evaluated differences among therapeutic regimens that include olmesartan in association with diuretics or amlodipine. These differences are due mainly to effects unrelated to the blood pressure-lowering effects of drugs used in combination with olmesartan, since both combinations are similar in their antihypertensive efficacy. This article reviews the effects of both combinations, bearing in mind several factors such as the metabolic risk of hypertensive patients, their age, blood pressure variability, and central blood pressure (AU)

Informe diário de evidências COVID-19: busca realizada em 25 de maio de 2020 / COVID-19 daily evidence report: search conducted on May 26, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referente ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 15 artigos e 10 protocolos.

Informe diário de evidências COVID-19: busca realizada em 17 de junho de 2020 / COVID-19 daily evidence report: search conducted on June 17, 2020

O Informe Diário de Evidências é uma produção do Ministério da Saúde que tem como objetivo acompanhar diariamente as publicações científicas sobre tratamento farmacológico e vacinas para a COVID-19. Dessa forma, são realizadas buscas estruturadas em bases de dados biomédicas, referente ao dia anterior desse informe. Não são incluídos estudos pré-clínicos (in vitro, in vivo, in silico). A frequência dos estudos é demonstrada de acordo com a sua classificação metodológica (revisões sistemáticas, ensaios clínicos randomizados, coortes, entre outros). Para cada estudo é apresentado um resumo com avaliação da qualidade metodológica. Essa avaliação tem por finalidade identificar o grau de certeza/confiança ou o risco de viés de cada estudo. Para tal, são utilizadas ferramentas já validadas e consagradas na literatura científica, na área de saúde baseada em evidências. Cabe ressaltar que o documento tem caráter informativo e não representa uma recomendação oficial do Ministério da Saúde sobre a temática. Foram encontrados 15 artigos.

COVID-19 e uso de inibidores da enzima conversora da angiotensina e bloqueadores dos receptores de angiotensina. Resumo científico. 7 de maio de 2020

Existem preocupações de que os inibidores da enzima conversora da angiotensina (inibidores da ECA) e os bloqueadores dos receptores de angiotensina (BRA) aumentem a susceptibilidade ao coronavírus SARS-CoV-2 (o agente viral que causa a doença COVID-19) e a probabilidade de doença COVID-19 grave.1 Essas preocupações se baseiam em considerações de plausibilidade biológica, e a observação de que há uma sobrerrepresentação dos pacientes com hipertensão e outras comorbidades cardiovasculares entre pacientes com COVID-19 com piores desfechos.3 Milhões de pessoas em todo o mundo estão em tratamento com inibidores da ECA e BRA para hipertensão, insuficiência cardíaca, doença coronariana ou doença renal. A especulação sobre piores desfechos entre pacientes em uso dessas medicações durante a pandemia de COVID-19 causou ansiedade generalizada entre pacientes e seus cuidadores. Por outro lado, os danos da retirada indiscriminada dessas medicações sobre desfechos cardiovasculares estão bem documentados. Também há uma especulação generalizada sobre os potenciais benefícios de inibidores da ECA e BRA, baseada em argumentos de plausibilidade biológica e dados em animais, além de pequenos estudos clínicos em pacientes com outras infecções respiratórias virais. Este resumo sumariza as evidências atuais sobre o impacto de inibidores de ECA ou bloqueadores de receptores de angiotensina sobre a síndrome respiratória aguda grave por SARS-CoV-2.

Insuficiencia cardiaca y trasplante / Heart failure and heart transplant

La Sección de Insuficiencia Cardiaca y Trasplante de la Sociedad Española de Cardiología tiene como misión el estudio, la potenciación y la difusión de todos los temas relacionados con el mundo de la disfunción miocárdica y el trasplante de corazón. La insuficiencia cardiaca es una enfermedad muy prevalente que consume gran cantidad de recursos sanitarios. Por ello, el interés de esta patología es máximo y las líneas de investigación, clínicas y básicas, así como los puntos de vista que intentan incrementar los conocimientos de esta enfermedad son múltiples. En este artículo se exponen las novedades más actuales relacionadas con esta enfermedad y sus tratamientos. En primer lugar, se analizan las últimas publicaciones relacionadas con la insuficiencia cardiaca crónica. Posteriormente, se revisan los estudios más recientes en materia de terapia de resincronización y los ensayos relacionados con la insuficiencia cardiaca aguda. En tercer lugar, se comentan las novedades en el campo de la disfunción cardiaca derecha, la hipertensión pulmonar y el Registro Español de Hipertensión Pulmonar. Para finalizar, se exponen los últimos conocimientos relacionados con la asistencia ventricular y el trasplante. Asimismo, se comentan los datos más relevantes que se extraen de los registros oficiales relacionados con el trasplante (Registro Español de Trasplante Cardiaco y Registro Español de Tumores Postrasplante Cardiaco) (AU)

The mission of the Heart Failure and Transplantation Section of the Spanish Society of Cardiology is to study, to promote interest in, and to disseminate information about all aspects of myocardial dysfunction and heart transplantation. Heart failure is a highly prevalent condition that consumes a substantial proportion of healthcare resources. Consequently, there is considerable interest in the disorder. Numerous lines of clinical and preclinical research are actively being pursued and new ways of increasing knowledge about the disease are constantly being explored. The aim of this article was to describe the most recent developments concerning heart failure and its treatment. Firstly, the latest publications on chronic heart failure are analyzed. Then, there is a review of the most recent studies on resynchronization therapy and of clinical trials on acute heart failure. Thirdly, new developments in right heart dysfunction and pulmonary hypertension, and the findings of the Spanish Pulmonary Hypertension Registry are discussed. Finally, the latest information on ventricular assist devices and heart transplantation is presented. In addition, the most important data obtained from official transplantation registries (i.e. the Spanish Heart Transplantation Registry and the Spanish Post-Heart Transplantation Tumor Registry) are reviewed (AU)

Angiotensin II up-regulates expression of inducible nitric oxide synthase in human umbilical endothelial cells: roles of AT1 and AT2 / 中华心血管病杂志

<p><b>OBJECTIVE</b>Angiotensin II is an important pro inflammation factor in the cardiovascular system. This experiment is aimed to study the effects of angiotensin II on inducible nitric oxide synthase expression in human umbilical endothelial cells.</p><p><b>METHODS</b>Human umbilical endothelial cells were cultured in vitro and treated with angiotensin II alone or in combination with AT1, AT2 and NF-kappaB inhibitors respectively. The inducible nitric oxide synthase expressions at protein and mRNA levels were measured with Western blot and reverse transcription-polymerase chain reaction (RT-PCR), and the activity of NF-kappaB was analyzed with EMSA.</p><p><b>RESULTS</b>Angiotensin II up-regulated inducible nitric oxide synthase expressions at the protein and mRNA levels at 5 h (P < 0.05), the activity of NF-kappaB was enhanced at 2 h (P < 0.05). These effects could be blocked by AT1 and NF-kappaB inhibitors but not by AT2 inhibitor.</p><p><b>CONCLUSION</b>Angiotensin II can upregulate the expression of inducible nitric oxide synthase through NF-kappaB pathway in human umbilical endothelial cells. AT1, other than AT2, play a key role in this process.</p>