Angioedema postoperatorio de inicio tardío, desencadenado por un inhibidor de la enzima convertidora de angiotensina: previsión de vía aérea de emergencia / Late-onset postoperative angioedema triggered by angiotensin-converting enzyme inhibitor: an emergent airway forethought

El angioedema es una situación potencialmente mortal, debido al riesgo de compromiso de la vía aérea que da lugar a un deterioro de la función respiratoria, hipoxia y, por último, paro cardiopulmonar. Puede ser provocado o desencadenado por agentes farmacéuticos, factores emocionales o fisiológicos, traumatismo de la vía aérea superior, o estrés quirúrgico.Un varón de 46 años de edad, a quien se había prescrito previamente perindopril, desarrolló angioedema de lengua 4h después de recibir el alta de la UCPA (unidad de cuidados postanestésicos). Se convocó a un equipo multidisciplinar, que destacó una estrategia de manejo de la vía aérea en caso de empeoramiento. Dicha estrategia consistió en intubación con fibroscopio por parte del anestesiólogo, o bien traqueostomía quirúrgica practicada por el equipo de cirugía, realizándose ambas técnicas con el paciente despierto y ventilación espontánea.El objetivo de este informe de caso es alertar de que el angioedema es una situación potencialmente mortal. Para un manejo óptimo, es importante preparar de antemano una estrategia detallada de manejo de la vía aérea, a implementar por parte de un equipo multidisciplinar. (AU)

Angioedema is a potentially life-threatening condition due to the risk of airway compromise leading to deterioration of respiratory function, hypoxia, and ultimately, cardiopulmonary arrest. It can be either unprovoked or triggered by pharmaceutical agents, emotional or physiologic factors, upper airway trauma, or surgical stress.A 46-year-old man previously prescribed perindopril developed angioedema of the tongue 4h after being discharged from the Post Anesthesia Care Unit (PACU). A multidisciplinary team was called and they outlined an airway management strategy to use in the event of worsening. The strategy consisted of either fiberoptic intubation by an anesthesiologist or surgical tracheostomy performed by the surgical team, both performed with the patient awake and in spontaneous ventilation.The aim of this case report is to raise awareness that angioedema is a potentially life-threatening condition. For optimal management, it is important to prepare in advance a detailed airway management strategy to be implemented by a multidisciplinary team. (AU)

Late-onset postoperative angioedema triggered by angiotensin-converting enzyme inhibitor: An emergent airway forethought.

Angioedema is a potentially life-threatening condition due to the risk of airway compromise leading to deterioration of respiratory function, hypoxia, and ultimately, cardiopulmonary arrest. It can be either unprovoked or triggered by pharmaceutical agents, emotional or physiologic factors, upper airway trauma, or surgical stress. A 46-year-old man previously prescribed perindopril developed angioedema of the tongue 4 h after being discharged from the Post Anesthesia Care Unit (PACU). A multidisciplinary team was called and they outlined an airway management strategy to use in the event of worsening. The strategy consisted of either fiberoptic intubation by an anesthesiologist or surgical tracheostomy performed by the surgical team, both performed with the patient awake and in spontaneous ventilation. The aim of this case report is to raise awareness that angioedema is a potentially life-threatening condition. For optimal management, it is important to prepare in advance a detailed airway management strategy to be implemented by a multidisciplinary team.

Angioedema por enalapril. Presentación de un caso

Los inhibidores de la enzima convertidora de angiotensina son utilizados por más de 40 millones de personas en todo el mundo para el tratamiento de enfermedades cardiovasculares. Son considerados seguros, aunque pueden producir angioedema severo en el 0,1 a 0, 5 % de los pacientes. Se presenta el caso de un paciente del sexo masculino, de 67 años de edad, con diagnóstico de diabetes mellitus e hipertensión arterial, tratado con metformina, hidroclorotiazida y enalapril desde hacía aproximadamente cuatro años, que ingresó en cuerpo de guardia con edema severo del tercio anterior de la lengua, sin compromiso respiratorio. Se indicó hidrocortisona y difenhidramina y evolucionó satisfactoriamente, por lo que fue dado de alta y se prescribió prednisona y difenhidramina por vía oral; se suspendió el enlapril y a las 48 horas se reevaluó y estaba asintomático. El mecanismo por el que estos medicamentos producen angioedema no está claro, pero probablemente sería por la acumulación tisular de bradiquinina y puede presentarse en cualquier momento del tratamiento. La correcta anamnesis, el diagnóstico precoz y el tratamiento inmediato con hidrocortisona por vía endovenosa son aspectos a considerar ante casos similares. El análisis del evento mediante la farmacovigilancia, permitió clasificarlo como severo, probablemente relacionado con el consumo de enalapril. Esto genera alertas para informar al personal de salud y tomar decisiones relacionadas con los medicamentos, que permitan la actuación inmediata con la finalidad de reducir la morbimortalidad.

Angiotensin converting enzyme inhibitors are used by more than 40 million people worldwide for the treatment of cardiovascular diseases. They are considered safe, although they can cause severe angioedema in 0.1 to 0.5% of patients. The case of a 67-years-old male patient diagnosed with diabetes mellitus and arterial hypertension, treated with metformin, hydrochlorothiazide and enalapril for approximately four years, who was admitted to the emergency room with severe edema of the third anterior of the tongue, without respiratory compromise is presented. Hydrocortisone and diphenhydramine were indicated and he evolved satisfactorily, for which he was discharged and prednisone and diphenhydramine were prescribed orally; he discontinued enlapril, 48 hours later he was reassessed and was asymptomatic. The mechanism by which these drugs produce angioedema is not clear, but it would probably be due to the tissue accumulation of bradykinin and can occur at any time during treatment. The correct history, early diagnosis and immediate treatment with intravenous hydrocortisone are aspects to consider in similar cases. Analysis of the event through pharmacovigilance allowed it to be classified as severe, probably related to the enalapril consumption. This generates alerts to inform health staff and make decisions related to medications, which allow immediate action in order to reduce morbidity and mortality.

Bloqueo del eje renina angiontensina aldosterona (RAAS) en la enfermedad renal diabética. Más allá del control de la hipertensión arterial / Renin angiotensin aldosterone system (RAAS) and its suppression in diabetic kidney disease. Control of arterial hypertension and beyond

La enfermedad renal diabética (ERD) es una comorbilidad con alta prevalencia a nivel mundial, siendo una de las complicaciones más frecuentes de la diabetes mellitus (DM). La ERD se relaciona con complicaciones cardiovasculares y progresión de la enfermedad renal crónica (ERC), por ello la identificación de factores modificables, como el control de la presión arterial, es uno de los pilares más importantes en el manejo integral. En esta revisión hacemos un recorrido sobre el papel de la hipertensión y el bloqueo del eje renina angiotensina aldosterona (RAAS) en el curso de la ERD y las estrategias terapéuticas orientadas a la reducción de la presión arterial (PA), el bloqueo RAAS y el impacto en resultados renales y cardiovasculares. El objetivo de este artículo es hacer una revisión de las intervenciones más importantes que actúan bloqueando el eje renina angiotensina aldosterona (RAAS) y determinar si estas medidas en los pacientes con ERD, solo tienen impacto en el control de la presión arterial o si también son estrategias de nefro y cardio-protección. Conclusión: La ERD es una de las complicaciones más frecuentes de la diabetes mellitus (DM). El control de la PA sigue siendo un pilar fundamental para lograr estos objetivos. Los bloqueadores del RAAS (iECAS y BRAs) son los antihipertensivos de elección con efecto terapéutico por el bloqueo RAAS y esto les permite tener además del control de la PA, efectos nefroprotectores y cardioprotectores importantes en pacientes con ERD, sobre todo cuando hay la presencia de albuminuria. Evaluamos que además de los inhibidores de la enzima convertidora de angiotensina (iECAs) y los bloqueadores del receptor de angiotensina (BRAs), vienen tomando importancia los antagonistas selectivos del receptor mineralocorticoide (ARM) como Finerenona.

Diabetic kidney disease (DKD) is a comorbidity with a high worldwide prevalence, and one of the most frequent complications of diabetes mellitus (DM). CKD is related to cardiovascular complications and the progression of chronic kidney disease (CKD), therefore the identification of modifiable factors, such as blood pressure control, is one of the most important pillars in comprehensive management. In this review, we will analyze the role of hypertension and the renin-angiotensin-aldosterone system (RAAS) and its suppression in the course of CKD, and therapeutic strategies aimed at reducing blood pressure (BP), RAAS blockade, and the impact on renal and cardiovascular outcomes. The objective of this article is to review the most important interventions that act by blocking the renin-angiotensin-aldosterone system (RAAS) and to determine if these measures in patients with CKD only have an impact on blood pressure control or if they are also nephron and cardio-protective strategies. Conclusion: DKD is one of the most frequent complications of diabetes mellitus (DM). BP control continues to be a fundamental pillar to achieve these objectives. RAAS blockers (iECAS and ARBs) are the first-line antihypertensive with a therapeutic effect due to RAAS blockade and this allows them to have, in addition to BP control, important nephroprotective and cardioprotective effects in patients with CKD, especially when there is albuminuria. We evaluated that in addition to angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), selective mineralocorticoid receptor antagonists (MRA) such as Finerenone are gaining importance.

Fast Skeletal Muscle Troponin and Tropomyosin as a Dietary Source of Antidiabetic and Antihypertensive Bioactive Peptides: An In Silico Study / Troponina y Tropomiosina de Músculo Esquelético como Fuente Alimentaria de Péptidos Bioactivos Antidiabéticos y Antihipertensivos: Estudio In Silico

Background: The nutraceutical properties of food hydrolysates rely on multiple biochemical interactions involving the modulation of enzymes and cellular receptors. Numerous bioactive peptides released from troponin and tropomyosin digestion have been identified. Their characterization has mostly been performed by hydrolysis catalyzed by proteases unrelated to the human digestive system. Objective: This study aimed to determine the bioactive profile of beef, pork, and chicken meat by analyzing the frequency and pharmacokinetics of biopeptides released from troponin and tropomyosin. Methods:In silico digestion and biopeptide release frequency were studied by three parameters; bioactive fragments release frequency (AE), frequency percentage (W), and mean occurrence (AS), all stated on the BIOPEP-UWM platform. Further on, hydrolysis end-products were screened based on gastrointestinal-absorption probability and pharmacokinetic profiling performed on SwissADME, SwissTargetPrediction, and ADME/Tlab bioinformatics web tools. Statistical analyses were performed using a one-way ANOVA test. Results: Dipeptidyl peptidase-IV (DPP-IV) and angiotensin-converting enzyme (ACE) inhibiting biopeptides exhibited the highest release frequency. Moreover, W and ASparameters showed no significant difference (p>0.05) between the myofibrillar isoforms assessed. Seven biopeptides were classified as highly absorbable and reported optimal drug-likeness compliance. Although biopeptides hold good pharmacokinetic properties, the therapeutic potency of biopeptides showed to be lower than those of DPP-IV and ACE-inhibiting drugs. Conclusions: Troponin and tropomyosin are rich dietary sources of bioactive peptides, mainly DPP-IV and ACE inhibitors. Digestion end-products are mainly dipeptides with optimal pharmacokinetic and drug-like properties, suggesting a potential therapeutic application in hypertensive and hyperglycemic disorders

Antecedentes: Las propiedades nutracéuticas de los hidrolizados de alimentos dependen de múltiples interacciones bioquímicos que involucran la modulación de enzimas y receptores celulares. Se han identificado numerosos péptidos bioactivos liberados de la digestión de troponina y tropomiosina, pero su caracterización se ha llevado a cabo principalmente por hidrólisis catalizada por proteasas ajenas al sistema digestivo humano. Objetivo: Este estudio tuvo como objetivo determinar el perfil bioactivo de la carne de res, cerdo y pollo mediante el análisis de la frecuencia y farmacocinética de los biopéptidos liberados de la troponina y la tropomiosina. Métodos: Se estudió la digestión in silico y la frecuencia de liberación de biopéptidos mediante dos parámetros; frecuencia de liberación de fragmentos bioactivos (AE), frecuencia porcentual (W) y ocurrencia media (AS), ambos indicados en la plataforma BIOPEP-UWM. Más adelante, los productos finales de la hidrólisis se examinaron en función de la probabilidad de absorción gastrointestinal y el perfil farmacocinético realizado en las herramientas bioinformáticas SwissADME, SwissTargetPrediction y ADME/Tlab. El análisis estadístico se llevó a cabo mediante una prueba ANOVA de una vía. Resultados: Los biopéptidos inhibidores de la dipeptidil peptidasa IV (DPP-IV) y la enzima convertidora de angiotensina (ECA) exhibieron la mayor frecuencia de liberación. Además, los parámetros W y ASno mostraron diferencias significativas (p> 0.05) entre las isoformas miofibrilares evaluadas. Siete biopéptidos se clasificaron como altamente absorbibles e informaron un cumplimiento óptimo de similitud con el fármaco. Aunque los biopéptidos tienen propiedades farmacocinéticas adecuadas, su potencia terapéutica demostró ser menor que la de los fármacos inhibidores de la DPP-IV y la ACE. Conclusiones: La troponina y la tropomiosina son una fuente dietética rica en péptidos bioactivos, principalmente DPP-IV e inhibidores de la ACE. Los productos finales de la digestión son principalmente dipéptidos con propiedades farmacocinéticas óptimas y similares a la de los fármacos, lo que sugiere una aplicación terapéutica factible en trastornos hipertensivos e hiperglicémicos

Chronic use of renin–angiotensin–aldosterone inhibitors in hypertensive COVID-19 patients: Results from a Spanish registry and meta-analysis / Uso crónico de los inhibidores del sistema renina-angiotensina-aldosterona en pacientes con COVID-19 e hipertensión arterial: Resultados de un registro español y metaanálisis

Background:Hypertension is a prevalent condition among SARS-CoV-2 infected patients. Whether renin–angiotensin–aldosterone system (RAAS) inhibitors are beneficial or harmful is controversial.Methods:We have performed a national retrospective, nonexperimental comparative study from two tertiary hospitals to evaluate the impact of chronic use of RAAS inhibitors in hypertensive COVID-19 patients. A meta-analysis was performed to strengthen our findings.Results:Of 849 patients, 422 (49.7%) patients were hypertensive and 310 (73.5%) were taking RAAS inhibitors at baseline. Hypertensive patients were older, had more comorbidities, and a greater incidence of respiratory failure (−0.151 [95% CI −0.218, −0.084]). Overall mortality in hypertensive patients was 28.4%, but smaller among those with prescribed RAAS inhibitors before (−0.167 [95% CI −0.220, −0.114]) and during hospitalization (0.090 [−0.008,0.188]). Similar findings were observed after two propensity score matches that evaluated the benefit of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers among hypertensive patients. Multivariate logistic regression analysis of hypertensive patients found that age, diabetes mellitus, C-reactive protein, and renal failure were independently associated with all-cause mortality. On the contrary, ACEIs decreased the risk of death (OR 0.444 [95% CI 0.224–0.881]). Meta-analysis suggested a protective benefit of RAAS inhibitors (OR 0.6 [95% CI 0.42–0.8]) among hypertensive COVID-19.Conclusion:Our data suggest that RAAS inhibitors may play a protective role in hypertensive COVID-19 patients. This finding was supported by a meta-analysis of the current evidence. Maintaining these medications during hospital stay may not negatively affect COVID-19 outcomes. (AU)

Introducción:La hipertensión es una condición prevalente entre los pacientes infectados por el SARS-CoV-2. Es controvertido si los inhibidores del sistema renina-angiotensina-aldosterona (SRAA) son beneficiosos o perjudiciales.Métodos:Hemos desarrollado un estudio comparativo nacional retrospectivo y no experimental en 2 hospitales terciarios para evaluar el impacto del uso crónico de inhibidores del SRAA en pacientes hipertensos con COVID-19. Se realizó un metaanálisis para reforzar los hallazgos.Resultados:De 849 pacientes, 422 (49,7%) eran hipertensos y 310 (73,5%) tomaban inhibidores del SRAA al inicio del estudio. Los pacientes hipertensos eran mayores, tenían más comorbilidades y una mayor incidencia de insuficiencia respiratoria (−0,151; IC 95%: [−0,218; −0,084]). La mortalidad global en los pacientes hipertensos fue del 28,4%, pero fue menor entre los que tenían prescritos inhibidores del SRAA antes (−0,167; IC 95%: [−0,220; −0,114]) y durante la hospitalización (0,090; [−0,008; 0,188]). Se observaron hallazgos similares tras 2 emparejamientos de puntuación de propensión que evaluaron el beneficio de los inhibidores de la enzima convertidora de angiotensina y los bloqueadores de los receptores de angiotensina entre los pacientes hipertensos. El análisis de regresión logística multivariante de los pacientes hipertensos reveló que la edad, la diabetes mellitus, la proteína C reactiva y la insuficiencia renal se asociaban de forma independiente con la mortalidad por todas las causas. Por el contrario, los inhibidores de la enzima convertidora de angiotensina disminuyeron el riesgo de muerte (OR 0,444; IC 95%: 0,224-0,881). El metaanálisis indicó un beneficio protector de los inhibidores del SRAA (OR 0,6; IC 95%: 0,42-0,8) entre los hipertensos con COVID-19. (AU)

Chronic use of renin-angiotensin-aldosterone inhibitors in hypertensive COVID-19 patients: Results from a Spanish registry and meta-analysis.

BACKGROUND: Hypertension is a prevalent condition among SARS-CoV-2 infected patients. Whether renin-angiotensin-aldosterone system (RAAS) inhibitors are beneficial or harmful is controversial. METHODS: We have performed a national retrospective, nonexperimental comparative study from two tertiary hospitals to evaluate the impact of chronic use of RAAS inhibitors in hypertensive COVID-19 patients. A meta-analysis was performed to strengthen our findings. RESULTS: Of 849 patients, 422 (49.7%) patients were hypertensive and 310 (73.5%) were taking RAAS inhibitors at baseline. Hypertensive patients were older, had more comorbidities, and a greater incidence of respiratory failure (-0.151 [95% CI -0.218, -0.084]). Overall mortality in hypertensive patients was 28.4%, but smaller among those with prescribed RAAS inhibitors before (-0.167 [95% CI -0.220, -0.114]) and during hospitalization (0.090 [-0.008,0.188]). Similar findings were observed after two propensity score matches that evaluated the benefit of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers among hypertensive patients. Multivariate logistic regression analysis of hypertensive patients found that age, diabetes mellitus, C-reactive protein, and renal failure were independently associated with all-cause mortality. On the contrary, ACEIs decreased the risk of death (OR 0.444 [95% CI 0.224-0.881]). Meta-analysis suggested a protective benefit of RAAS inhibitors (OR 0.6 [95% CI 0.42-0.8]) among hypertensive COVID-19. CONCLUSION: Our data suggest that RAAS inhibitors may play a protective role in hypertensive COVID-19 patients. This finding was supported by a meta-analysis of the current evidence. Maintaining these medications during hospital stay may not negatively affect COVID-19 outcomes.

Manejo del angiodema inducido por inhibidores de la enzima convertidora de angiotensina con icatibant / Management of angiotensin-converting enzyme inhibitors-related angioedema with icatibant

Objetivo: Evaluar la efectividad de icatibant en el tratamiento del angioedema inducido por IECA (AII), en un centro sin protocolización previa del manejo.Método: Estudio observacional retrospectivo y descriptivo. Se incluyeron pacientes diagnosticados de AII y tratados con icatibant 30 mg entre mayo 2015-diciembre 2017. Las variables de resultado principal y secundaria fueron: tiempo hasta resolución completa y tiempo hasta primera mejoría; respectivamente.Resultados: Cinco pacientes, mediana de edad 76 años (46-81); cuatro mujeres y un varón. Todos caucásicos. Medianas de tiempo hasta resolución completa y hasta primera mejoría: 23 horas (IQR 20,0-25,0) y 3 horas (IQR 3,0-6,0); respectivamente.Conclusiones. El inicio temprano del tratamiento anti-bradicinérgico puede resultar clave para la evolución del cuadro. Para alcanzar la máxima efectividad, se reduzcan las morbilidades asociadas, los ingresos en UCI y el tiempo de estancia hospitalaria, resulta primordial la elaboración de protocolos locales que tengan en cuenta las particularidades de cada centro. (AU)

Objetive: To assess the effectiveness of icatibant in the management of angiotensin-converting enzyme inhibitor-induced angioedema (AII) in a hospital without a treatment guidance.Methods: Observational, retrospective and descriptive study. All patients diagnossed with AII and treated with icatibant 30 mg between May 2015-December 2017 were included. The primary and secondary end-points were: time to total resolution and time to first improvement; respectively.Results: Five patients, median age 76 years (46-81). Four women and a man. All of them Caucasian. Median time to total resolution and to first improvement: 23 hours (IQR 20.0-25.0) and 3 hours (IQR 3.0-6.0); respectively.Conclusion: The early start with the anti-bradicinergic therapy may be key to the AII evolution. To achieve the maximum effectiveness and to get reduced the associated morbidity, the ICU admission and the time to discharge, the development of local protocols considering the particularities of each center is highly necessary. (AU)

Pronóstico de los pacientes hospitalizados por Covid-19 que utilizaban inhibidores de la enzima convertidora de angiotensina o antagonistas del receptor de angiotensina II / Prognósis of patients hospitalized due to Covid-19 who were taking angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers

Introducción: existe controversia acerca de la seguridad del uso de inhibidores de la enzima convertidora de angiotensina (iECA) o antagonistas de los receptores de angiotensina II (ARA II) en pacientes con COVID-19, debido a que la ECA-2 sirve de entrada del virus a la célula. Objetivo: evaluar la asociación del antecedente del uso de iECA o ARA II con el ingreso a UCI o la muerte intrahospitalaria. Metodología: cohorte prospectiva multicéntrica que incluyó pacientes adultos hospitalizados por coronavirus COVID-19 en tres hospitales de Bogotá, Colombia, entre abril y noviembre 2020. Se realizó un análisis univariado evaluando la asociación de los iECA y ARA II con el ingreso a UCI o la muerte intrahospitalaria. Resultados: se incluyeron 592 pacientes de los cuales 225 (38.0%) cursaban con hipertensión arterial, 108 (18.2%) diabetes y 50 (8.4%) enfermedad cardiovascular crónica, 160 (27.0%) ingresaron a UCI y 107 (18.1%) fallecieron, 32% tenía el antecedente de uso de iECA o ARA II. En el análisis univariado no se obtuvo ninguna asociación con ingreso a UCI o muerte intrahospitalaria, uso de inhibidores de la ECA OR= 1.017 (IC95% 0.887 - 1.152, p=0.800), OR=1.072 (0.952 - 1.19, p=0.968) respectivamente; uso de ARA II OR= 0.998 (IC95% 0.913-1.086, p=0.968), OR=1.045 (IC95% 0.969 - 1.122, p=0.235), respectivamente. Conclusiones: el antecedente del uso de los iECA o ARA II no se asoció con el ingreso a UCI o la muerte intrahospitalaria en pacientes hospitalizados por COVID-19.

Introduction: controversy remains about the safety of using angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) in patients with COVID-19, since ACE2 receptor mediates the entry of the virus into the cell. Objective: to evaluate the association of past history of ACEIs or ARBs use with admission to the ICU or in-hospital death. Methodology: prospective multicenter cohort that included adult patients hospitalized due to COVID-19 coronavirus in three hospitals in Bogota, Colombia, between April and November 2020. A univariate analysis was performed evaluating the association of ACEIs and ARBs with ICU admission or in-hospital death. Results: 592 patients were included of whom 225 (38.0%) had hypertension, 108 (18.2%) diabetes and 50 (8.4%) chronic cardiovascular disease, 160 (27.0%) were admitted to the ICU and 107 (18.1%) died, 32% had a history of prior ACEIs or ARBs use. In the univariate analysis no association was found with ICU admission or in-hospital death, ACEIs use OR= 1.017 (CI95% 0.887 - 1.152, p=0.800), OR=1.072 (0.952 - 1.19, p=0.968) respectively; use of ARBs OR= 0.998 (CI95% 0.913-1.086, p=0.968), OR=1.045 (CI95% 0.969 - 1.122, p=0.235), respectively. Conclusions: a history of prior ACEIs or ARBs use was not associated with admission to the ICU or in-hospital death in patients hospitalized due to COVID-19.

COVID-19 e hipertensión arterial: ¿existe evidencia para suspender antagonistas del sistema renina-angiotensina-aldosterona? / COVID-19 and arterial hypertension: is there evidence to suspend renin-angiotensin-aldosteronesystem blockade?

Resumen El nuevo coronavirus SARS-CoV-2, causante de la enfermedad COVID-19, presenta una alta mortalidad en pacientes con enfermedades cardiovasculares, diabetes e hipertensión, trastornos que comparten la fisiopatología subyacente relacionada con el sistema renina-angiotensina (RAS). El SARS-CoV-2 utiliza la proteína de la membrana angiotensina I y convierte a la enzima convertidora de angiotensina tipo 2 (ACE2) en un receptor de entrada celular; por tanto, el RAS, regulado por ACE y ACE2, puede verse alterado en pacientes con COVID-19. Sin embargo, aún no es claro si el uso de fármacos antihipertensivos inhibidores de la ACE2 y bloqueadores del receptor de angiotensina II podría potencializar el daño ocasionado por el virus o contrarrestar su efecto, sobre todo a nivel pulmonar. El desafío se ve agravado por la información exagerada publicada en diferentes revistas científicas, la cual podría llevar a acciones inapropiadas, por lo que es importante diferenciar rápidamente la verdadera epidemia de hipótesis falsas, que podría llevar a conductas medicas potencialmente dañinas.

Abstract The new coronavirus SARS-CoV-2, which causes the disease COVID-19, has a high mortality in patients with cardiovascular diseases, diabetes and hypertension, disorders that share the underlying pathophysiology related to the renin-angiotensin system (RAS). SARS-CoV-2 uses the membrane protein angiotensin I and converts angiotensin converting enzyme type 2 (ACE2) into a cellular entry receptor, therefore, RAS, regulated by ACE and ACE2, can be altered in COVID-19 patients. However, it is not yet clear whether the use of antihypertensive drugs ACE2 inhibitors and angiotensin II receptor blockers could potentiate the damage caused by the virus or counteract its effect, especially in the lungs. The challenge is compounded by the exaggerated information published in different scientific journals, which could lead to inappropriate actions, so it is important to quickly differentiate the true epidemic from false hypotheses, which could lead to potentially harmful medical behaviors.

Uso terapéutico de los inhibidores de la enzima convertidora de angiotensina en pacientes con COVID-19: las «dos caras de la moneda¼ / Therapeutic use of angiotensin converting enzyme inhibitors in patients with COVID-19: the "two sides of the coin"

Resumen La evidencia actual es limitada para determinar el impacto del uso de los inhibidores de la enzima convertidora de angiotensina (IECA) en la predisposición al empeoramiento de la enfermedad del coronavirus 2019 (COVID-19). Inicialmente se reportó que en los pacientes con progresión grave de la COVID-19 existía una mortalidad elevada, los cuales tenían antecedentes de hipertensión arterial, diabetes mellitus, enfermedad cardiovascular y enfermedad renal crónica. Parte de estos pacientes también tenía en común que utilizaban IECA, lo cual alertó a la comunidad médica sobre su riesgo potencial en coexistencia con COVID-19. Sin embargo, estudios más recientes de casos-controles encontraron que los inhibidores del sistema renina-angiotensina, incluyendo los IECA, no incrementan el riesgo de COVID-19 o de requerir admisión hospitalaria por esta causa. Diferentes revistas científicas han facilitado el acceso a reportes preliminares, dejando a discreción de la comunidad médica y científica hacer uso de dicha información para promover el desarrollo de estudios que confirmen experimentalmente dichos hallazgos, preclínicos y epidemiológicos, que finalmente impacten en las decisiones de la práctica clínica para beneficiar a los pacientes con COVID-19. En esta revisión de la literatura se exploran los diferentes efectos mediados por los IECA que podrían estar relacionados con la respuesta inmune durante la infección y la transmisión de COVID-19, compilando evidencia disponible que evalúa si en realidad representan un riesgo o si, por el contrario, confieren un efecto protector.

Abstract There is limited evidence for determining the impact of the use of angiotensin converting enzyme inhibitors (ACE-I) in the tendency to worsening of coronavirus-19 disease (COVID-19). It was initially reported that, in patients with serious progression of COVID-19, there was an increased mortality in those that had a history of suffering arterial hypertension, diabetes mellitus, cardiovascular disease, and chronic kidney disease. A proportion of these patients also had in common that they used ACE-I, which alerted the medical community on the potential risk in coexisting with COVID-19. However, in more recent case-control studies, they found that inhibitors of the renin-angiotensin system, including ACE-I, does not increase the risk of COVID-19 or require hospital admission due to this cause. Several scientific journals have provided access to preliminary reports, leaving the use of such information at the discretion of the medical and scientific community for promoting the development of studies that might confirm these preclinical and epidemiological findings experimentally. These may finally have an impact on the clinical practice decisions, in order to benefit patients with COVID-19. In this literature review, the different effects mediated by ACE-I that could be related to the immune response during the infection and transmission of COVID-19 are examined, gathering available evidence that evaluates whether, in reality, they represent a risk or if on the other hand, they confer a protector effect.

[Risk of severe COVID-19 in hypertensive patients treated with renin-angiotensin-aldosterone system inhibitors]. / Riesgo de COVID-19 grave en pacientes hipertensos tratados con inhibidores del sistema renina-angiotensina-aldosterona.

INTRODUCTION: There is controversy concerning the use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II type-I receptor blockers (ARB) for treating hypertensive patients with Covid-19. It has been hypothesized that these drugs might increase the risk of severe Covid-19, but some authors suggested that blocking the renin-angiotensin system might actually decrease this risk. METHODS: Retrospective cohort study of all the consecutive hypertensive patients with confirmed SARS-CoV-2 infection in a health area. The outcome variable was hospitalization because of severe Covid-19. RESULTS: 539 subjects were diagnosed of SARS-CoV-2 infection. Of these, 157 (29.1%) had hypertension and were included in the study. Sixty-nine cases (43.9%) were hospitalized because of severe Covid-19. In multivariable analysis older age, diabetes and hypertensive myocadiopathy were related to a higher risk of hospital admission. ARB treatment was associated with a significantly lower risk of hospitalization (HR: 0.29, 95% CI: 0.10 - 0.88). A similar albeit not significant trend was observed for ACEI. CONCLUSION: ARB or ACEI treatment was not associated with a worse clinical outcome in consecutive hypertensive patients infected by SARS-CoV-2.

[The RAAS and SARS-CoV-2: A riddle to solve]. / El SRAA y el SARS-CoV-2: el acertijo a resolver.

The first case of COVID-19 was reported on 31 December 2019 in Wuhan, China. Ever since there has been unprecedented and growing interest in learning about all aspects of this new disease. Debate has been generated as to the association between antihypertensive therapy with renin-angiotensin-aldosterone system (RAAS) inhibitors and SARS-CoV-2 infection. While many questions as yet remain unanswered, the aim of this report is to inform health professionals about the current state of knowledge. Because this is an ever-evolving topic, the recommendation is that it be updated as new evidence becomes available. Below, we provide a review of pre-clinical and clinical studies that link coronavirus to the RAAS.

The renin-angiotensin-aldosterone system and its inhibitors in the context of the COVID-19 pandemic.

Una de las confusiones que ha generado la pandemia de COVID-19 es la idea de que los inhibidores de la enzima convertidora de la angiotensina y los antagonistas del receptor de la angiotensina II de tipo 1 pueden agravar el daño pulmonar inducido por el SARS-CoV-2 en pacientes de edad avanzada. En este breve comunicado se analiza, desde una perspectiva crítica, la evidencia científica que secunda esta asociación.One of the confusions aroused by the outbreak of COVID-19 pandemic is the idea that angiotensin converting enzyme inhibitors and type 1 angiotensin II receptor may aggravate the lung damage induced by SARS CoV-2 virus in older adult patients. In this brief statement, the scientific evidence supporting this association is analyzed from a critical perspective.

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)

Effects of angiotensin II receptor blockers and angiotensin-converting enzyme inhibitors on COVID-19: a narrative review of the literature / Efectos de bloqueadores del receptor de angiotensina II e inhibidores de la enzima convertidora de angiotensina en COVID-19: una revisión narrativa de la literatura / Efeitos dos bloqueadores do receptor da angiotensina II e inibidores da enzima de conversão da angiotensina no COVID-19: uma revisão narrativa da literatura

Introduction: An outbreak of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) is currently affec-ting worldwide. The association between this virus and the upregulation of Angiotensin-Converting Enzyme 2 (ACE2) has been suggested as a potential as an important factor in the development of Coronavirus Disease- 19 (COVID-19). Objective: To describe the relationship between some antihypertensive treatments and COVID-19. Methods: A research was conducted with the components of the PIO (Population, Intervention, Outcomes) strate-gy, including the literature of the last 20 years available in central PubMed, Web of Science, Scopus, and Embase databases. All relevant articles that assessed the epidemiological relationship between SARS-CoV-2 and hyperten-sion, the treatment and outcomes of the patients who have this comorbidity, as well as the relationship between the RAA axis and COVID-19 were included in the analysis. Results: A total of 292 items were found in the databases. After a thorough analysis, 17 papers were selected, including in vitro and in vivo tests, clinical trials, and epidemiological studies related to the topic analyzed. Conclusion: Due to the systemic benefits of antihypertensive drugs targeting the RAA axis, and the lack of eviden-ce of these treatments being a risk factor, It is not recommended to withdraw these medications from hypertensive patients infected with SARS-CoV 2, unless there is a clinical indication.

Introducción: el surgimiento y diseminación del coronavirus tipo 2 del síndrome respiratorio agudo severo (SARS-CoV-2), actualmente, afecta a la mayoría de los del mundo. La asociación entre este virus y la regulación positiva de la enzima convertidora de angiotensina 2 (ACE2) se ha sugerido como un factor potencial en el desarrollo de la enfermedad por coronavirus-19 (COVID- 19). Objetivo: describir la relación entre algunos tratamientos antihipertensivos y la COVID-19. Métodos: se revisaron los componentes de la estrategia PIO (población, intervención, resultados). Se incluyeron todos los artículos relevantes de los últimos 20 años disponibles en las bases de datos centrales PubMed, Web of Science, Scopus y Embase, que describen la relación epidemiológica entre SARS-CoV-2 e hipertensión, el tratamiento y el desenlace de los pacientes quienes tienen esta comor-bilidad, así como la relación entre el eje renina-angiotensina-aldosterona y COVID-19. Resultados: se encontraron inicialmente 292 artículos en las bases de datos, para finalmente seleccio-nar 17 artículos, incluyendo exámenes in vivo e in vitro, ensayos clínicos y estudios epidemiológicos relacionados con el tema analizado. Conclusión: debido a los beneficiosos efectos sistémicos del tratamiento antihipertensivo, cuyo blanco es el sistema renina-angiotensina- aldosterona, y a la falta de evidencia acerca de estos me-dicamentos en cuanto a la inducción de SARS-CoV-2, no se recomienda suspender o contraindicar el tratamiento con estos fármacos en pacientes hipertensos positivos para COVID-19, a menos que haya una indicación clínica

Introdução: Um surto de Síndrome Respiratória Aguda Grave Coronavirus 2 (SARS-CoV-2) está afe-tando atualmente em todo o mundo. A associação entre esse vírus e a suprarregulação da Enzima Conversora da Angiotensina 2 (ACE2) tem sido sugerida como um fator potencial importante no de-senvolvimento da Doença do Coronavírus-19 (COVID-19). Objetivo: Descrever a relação entre al-guns tratamentos anti-hipertensivos e COVID-19. Métodos: Foi realizada uma pesquisa com os com-ponentes da estratégia Population, Intervention, Resultados (PIR), incluindo a literatura dos últimos 20 anos disponível nas bases de dados centrais PubMed, Web of Science, Scopus e Embase. Todos os artigos relevantes que avaliaram a relação epide-miológica entre SARS-CoV-2 e hipertensão, o trata-mento e resultados dos pacientes que apresentam essa comorbidade, bem como a relação entre o eixo RAA e COVID-19 foram incluídos na análise. Resultados: Foram encontrados 292 itens nas bases de dados. Após análise aprofundada, foram selecionados 17 artigos, entre testes in vitro e in vivo, en-saios clínicos e estudos epidemiológicos relacionados ao tema analisado. Conclusão: Devido aos be-nefícios sistêmicos dos medicamentos anti-hipertensivos direcionados ao eixo RAA e à falta de evi-dência desses tratamentos serem um fator de risco, não é recomendado retirar esses medicamentos de pacientes hipertensos infectados com SARS-CoV 2, a menos que haja um indicação clínica.

Reduced Frequency of Bone Pain Crises in Patients with Sickle Cell Disease Given an Angiotensin-converting Enzyme Inhibitor / Reducción de la frecuencia de la crisis de dolor óseo en pacientes con la enfermedad de células falciformes mediante los inhibidores de la enzima convertidora de angiotensina

ABSTRACT Objective: To determine if sickle cell disease (SCD) bone pain crisis is mitigated by use of an angiotensin-converting enzyme inhibitor (ACEI), following a case report of ACEIs preventing bone pain crisis. Methods: Patients with SCD who attended the Haematology Clinic at Jos University Teaching Hospital, Nigeria, were assessed with a questionnaire, given 2.5 mg of ramipril and followed up monthly for three months. Frequencies of bone pain crises in the month preceding enrolment and three months following treatment as well as the cardiovascular status were evaluated. Results: Thirty-five patients with complete data were reported. Blood pressure remained stable, and cumulative frequency of bone pain crises fell. The relative risk reduction for bone pain was 56.2% at one month, 63.0% at two months and 13.0% at three months. Conclusion: Vaso-occlussion-induced hypoxia, triggering bone pain crises, produces angiotensin II from angiotensin and worsens vasoconstriction. Angiotensin-converting enzyme inhibitors block this process, reducing severity or preventing bone pain crises. With these observations and a stable blood pressure profile, we recommend wider use of ACEIs in patients with SCD to cut down on the need of opioid use with attendant addiction risk, as a way of improving their quality of life.

RESUMEN Objetivo: Determinar si la crisis de dolor por la enfermedad de células falciformes (ECF) es mitigada con el uso de los inhibidores de la enzima convertidora de angiotensina (IECA), luego de un informe que reporta que IECA previene la crisis del dolor óseo. Métodos: A pacientes con ECF que asistían a la Cínica de Hematología del Hospital Docente de la Universidad de Jos, Nigeria, se les evaluó con un cuestionario, se les suministró 2.5 mg de ramipril, y se les hizo un seguimiento mensual por tres meses. Se evaluaron las frecuencias de las crisis de dolor óseo en el mes anterior al alistamiento y tres meses después del tratamiento, así como el estado cardiovascular. Resultados: Se reportaron treinta y cinco pacientes con datos completos. La presión sanguínea se mantuvo estable, en tanto que se produjo un descenso de la frecuencia cumulativa de las crisis de dolor óseo. La reducción del riesgo relativo del dolor óseo fue de 56.2% en un mes, 63.0% en dos meses, y 13.0% en tres meses. Conclusión: La hipoxia inducida por vaso-oclusión, que desencadena la crisis de dolor óseo, produce angiotensina II a partir de la angiotensina y empeora la vasoconstricción. Los inhibidores de la enzima convertidora de angiotensina bloquean este proceso, reduciendo la severidad o previniendo las crisis del dolor óseo. Con estas observaciones y un perfil de presión arterial estable, recomendamos hacer un amplio uso de IECA en pacientes con ECF para reducir la necesidad del consumo de opioides y el consiguiente riesgo de adicción, como una manera de mejorar su calidad de vida.

A high sodium intake reduces antiproteinuric response to renin-angiotensin-aldosterone system blockade in kidney transplant recipients. / La ingesta elevada de sodio disminuye la respuesta antiproteinúrica del bloqueo del eje renina-angiotensina-aldosterona en el trasplante renal.

BACKGROUND: Post-transplant proteinuria is associated with lower graft and patient survival. Renin-angiotensin-aldosterone system blockers are used to reduce proteinuria and improve renal outcome. Although it is known that a high salt intake blunts the antiproteinuric effect of ACEI and ARB drugs in non-transplant patients, this effect has not been studied in kidney transplant recipients. OBJECTIVE: To analyse the relationship between sodium intake and the antiproteinuric effect of ACEI/ARB drugs in kidney transplant recipients. METHODS: We selected 103 kidney transplant recipients receiving ACEI/ARB drugs for more than 6 months due to proteinuria>1 g/day. Proteinuria was analysed at baseline and at 6 months after starting ACEI/ARB treatment. Salt intake was estimated by urinary sodium to creatinine ratio (uNa/Cr). RESULTS: Proteinuria fell to less than 1g/day in 46 patients (44.7%). High uNa/Cr was associated with a smaller proteinuria decrease (r=-0.251, P=.011). The percentage proteinuria reduction was significantly lower in patients in the highest uNa/Cr tertile [63.9% (IQR 47.1%), 60.1% (IQR 55.4%), 38.9% (IQR 85.5%), P=.047]. High uNa/Cr independently relates (OR 2.406 per 100 mEq/g, 95% CI: 1.008-5.745, P=.048) to an antiproteinuric response <50% after renin-angiotensin-aldosterone system blockade. CONCLUSIONS: A high salt intake results in a smaller proteinuria decrease in kidney transplant recipients with proteinuria treated with ACEI/ARB drugs.

[Association between visual improvement after photocoagulation and the use of angiotensin converting enzyme inhibitors in diabetic macular oedema]. / Asociación entre la mejoría visual y el uso de inhibidores de la enzima convertidora de angiotensina, en edema macular diabético.

BACKGROUND: Angiotensin converting enzyme inhibitors are effective in delaying the progression of diabetic retinopathy. It is unknown if their use is associated with a better visual outcome in patients with diabetic macular oedema. MATERIAL AND METHODS: A non-experimental, comparative, longitudinal and retrospective study was performed on patients with diabetic macular oedema treated by focal photocoagulation, and with systemic arterial hypertension treated with angiotensin converting enzyme inhibitors (Group 1), and without hypertension (Group 2). The dependent variable was the proportion with visual improvement, operatively defined as the gain of one or more lines of vision three weeks after photocoagulation. The independent variable was the use of angiotensin converting enzyme inhibitors. The proportion of eyes with visual improvement after treatment was compared between groups using the Chi squared (χ(2)) test. RESULTS: A total of 33 eyes (51.6%) were assigned to group 1, and 31 (48.2%), to group 2. The mean of visual acuity improved after three weeks, compared with baseline (p=0.002). The proportion of eyes with visual improvement did not differ between patients treated with angiotensin converting enzyme inhibitors (45.5%) and those that did not use them (51.6%, p=0.4). CONCLUSIONS: There was no statistical difference in the proportion of eyes with visual improvement between patients treated with angiotensin converting enzyme inhibitors and in those where they were not used. There is no support for the inhibition of angiotensin II in addition to photocoagulation for improving the outcome in patients with diabetic macular oedema.

Betabloqueantes e inhibidores del sistema renina-angiotensina-aldosterona en el síndrome coronario agudo / Beta-blockers and inhibitors of the renin-angiotensin-aldosterone system in acute coronary syndrome

Los betabloqueantes y los inhibidores de la enzima convertidora de angiotensina / antagonistas de los receptores de angiotensina II (I-ECA/ARA II) son medicamentos esenciales en el manejo del síndrome coronario agudo (SCA) con un efecto beneficioso en la sobrevida, aditivo al obtenido con otros fármacos, como aspirina y estatinas, reduciendo la morbi-mortalidad temprana y tardía en pacientes revascularizados o no. Los pacientes pos IAM con fracción de eyección del ventrículo izquierdo (FEVI) < 40% e insuficiencia cardíaca o diabetes, se pueden beneficiar del tratamiento con antagonistas de los receptores mineralocorticoides si se aplican en forma temprana.