Revisión sistemática
Medwave 2021;21(02):e8105 doi: 10.5867/medwave.2021.02.8105
Inhibidores de la enzima convertidora de la angiotensina y antagonistas del receptor de angiotensina II para COVID-19: Una revisión sistemática viviente de ensayos clínicos aleatorizados
Angiotensin-converting-enzyme inhibitors and angiotensin II receptor blockers for COVID-19: A living systematic review of randomized clinical trials
Nicolás Meza, Javier Pérez-Bracchiglione, Ignacio Pérez, Cristhian Carvajal , Luis Ortiz-Muñoz, Pablo Olguín , Gabriel Rada, Eva Madrid
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Palabras clave: COVID-19, severe acute respiratory syndrome coronavirus 2, coronavirus infections, systematic review, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers

Resumen

Objetivo
Esta revisión sistemática viva tiene como objetivo proporcionar un resumen oportuno, riguroso y continuamente actualizado de la evidencia disponible sobre el rol de los inhibidores de la enzima convertidora de angiotensina (iECA) y los bloqueadores del receptor de angiotensina II (ARA-II) en el tratamiento de pacientes con COVID-19.

Fuentes de datos
Realizamos búsquedas en PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), literatura gris y en el repositorio centralizado L·OVE (Living OVerview of Evidence) que recupera artículos de múltiples fuentes como PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, Embase, entre otros repositorios de preprints y protocolos. En respuesta a la emergencia de COVID-19, L·OVE (Living OVerview of Evidence) se adaptó para ampliar el rango de información que cubre y se personalizó para agrupar toda la evidencia en torno a COVID-19 en un solo lugar, en una base de búsqueda diaria. La búsqueda cubrió el período hasta el 31 de julio de 2020.

Criterios de elegibilidad para la selección de estudios y métodos
Adaptamos un protocolo común ya publicado para múltiples revisiones sistemáticas vivas paralelas a las especificidades de esta pregunta. Se incluyeron ensayos aleatorizados que evaluaban el efecto de la suspensión o la indicación de inhibidores de la enzima convertidora de angiotensina o bloqueadores de los receptores de angiotensina II, como monoterapia o en combinación, versus placebo o ningún tratamiento, en pacientes con COVID-19. Se buscaron ensayos aleatorizados que evaluaran el efecto de los inhibidores de la enzima convertidora de angiotensina/bloqueadores del receptor de angiotensina II versus placebo o ningún tratamiento en pacientes con COVID-19. Dos revisores examinaron de forma independiente la elegibilidad de cada estudio, extrajeron los datos y evaluaron el riesgo de sesgo. Los resultados se agruparon mediante un metanálisis y se aplicó GRADE para evaluar la certeza de la evidencia para cada resultado. Cada vez que cambien las conclusiones o hayan actualizaciones sustanciales, volveremos a enviar un reporte.

Resultados
Analizamos 772 artículos, pero ninguno cumplió con los criterios de inclusión. Identificamos 55 estudios en curso, incluidos 41 ensayos aleatorizados que evaluaban inhibidores de la enzima convertidora de angiotensina/bloqueadores del receptor de angiotensina II para pacientes con COVID-19.Analizamos 772 artículos, pero ninguno cumplió con los criterios de inclusión. Identificamos 55 estudios en curso, incluidos 41 ensayos aleatorizados que evaluaban inhibidores de la enzima convertidora de angiotensina/bloqueadores del receptor de angiotensina II para pacientes con COVID-19.

Conclusiones
No encontramos ningún ensayo clínico aleatorizado que cumpliera con nuestros criterios de inclusión y, por lo tanto, no hay pruebas que respalden el papel de los inhibidores de la enzima convertidora de angiotensina y los bloqueadores de los receptores de angiotensina II en el tratamiento de pacientes con COVID-19. Identificamos un número considerable de estudios en curso que podría proporcionar evidencia valiosa para informar a los investigadores y a los responsables de la toma de decisiones en un futuro próximo.


 

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Objective
This living systematic review aims to provide a timely, rigorous, and continuously updated summary of the evidence available on the role of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) in the treatment of patients with COVID-19.

Data sources
We conducted searches in PubMed/Medline, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), grey literature and in a centralized repository in L·OVE (Living OVerview of Evidence), which retrieves articles from multiple sources such as PubMed/MEDLINE, Cochrane Central Register of Controlled Trials, Embase, among other pre-print and protocols repositories. In response to the COVID-19 emergency, L·OVE (Living OVerview of Evidence) was adapted to expand the range of evidence and customized to group all COVID-19 evidence in one place on a daily search basis. The search covered a period of time up to July 31, 2020.

Eligibility criteria for selecting studies and methods
We adapted an already published standard protocol for multiple parallel living systematic reviews to this question's specificities. We included randomized trials evaluating the effect of either suspension or indication of angiotensin-converting-enzyme inhibitors or angiotensin II receptor blockers as monotherapy, or in combination versus placebo or no treatment in patients with COVID-19. We searched for randomized trials evaluating the effect of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers versus placebo or no treatment in patients with COVID-19. Two reviewers independently screened each study for eligibility, extracted data, and assessed the risk of bias. We pooled the results using meta-analysis and applied the GRADE system to assess the certainty of the evidence for each outcome. We will resubmit results every time the conclusions change or whenever there are substantial updates.

Results
We screened 772 records, but none was considered for eligibility. We identified 55 ongoing studies, including 41 randomized trials evaluating angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers for patients with COVID-19.

Conclusions
We did not find a randomized clinical trial meeting our inclusion criteria, and hence there is no evidence for supporting the role of angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers in the treatment of patients with COVID-19. A substantial number of ongoing studies would provide valuable evidence to inform researchers and decision-makers in the near future.

PROSPERO registration number
CRD42020182495

Protocol preprint DOI
10.31219/osf.io/vp9nj

Autores: Nicolás Meza[1], Javier Pérez-Bracchiglione[1], Ignacio Pérez[2], Cristhian Carvajal [2], Luis Ortiz-Muñoz[3], Pablo Olguín [2], Gabriel Rada[3,4,5], Eva Madrid[1], COVID-19 L·OVE Working Group

Colaboradores:

Filiación:
[1] Interdisciplinary Centre for Health Studies (CIESAL), Universidad de Valparaíso, Cochrane Chile Associate Centre, Viña del Mar, Chile
[2] School of Medicine, Cochrane Chile Associate Centre, Universidad de Valparaíso, Viña del Mar, Chile
[3] UC Evidence Center, Cochrane Chile Associate Center, Pontificia Universidad Católica de Chile, Santiago, Chile
[4] Fundación Epistemonikos, Santiago, Chile
[5] Internal Medicine Department, Faculty of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile

E-mail: eva.madrid@uv.cl

Correspondencia a:
[1] Angamos 655
Reñaca, Viña del Mar, Chile

Citación: Meza N, Pérez-Bracchiglione J, Pérez I, Carvajal C, Ortiz-Muñoz L, Olguín P, et al. Angiotensin-converting-enzyme inhibitors and angiotensin II receptor blockers for COVID-19: A living systematic review of randomized clinical trials. Medwave 2021;21(02):e8105 doi: 10.5867/medwave.2021.02.8105

Fecha de envío: 5/8/2020

Fecha de aceptación: 11/12/2020

Fecha de publicación: 3/3/2021

Origen: No solicitado

Tipo de revisión: Con revisión por pares externa, por tres árbitros a doble ciego

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Fang L, Karakiulakis G, Roth M. Are patients with hypertension and diabetes mellitus at increased risk for COVID-19 infection? Lancet Respir Med. 2020 Apr;8(4):e21. | CrossRef | PubMed |

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Wu C, Chen X, Cai Y, Xia J, Zhou X, Xu S, et al. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern Med. 2020 Jul 1;180(7):934-943. | CrossRef | PubMed |

Guo J, Huang Z, Lin L, Lv J. Coronavirus Disease 2019 (COVID-19) and Cardiovascular Disease: A Viewpoint on the Potential Influence of Angiotensin- Converting Enzyme Inhibitors/Angiotensin Receptor Blockers on Onset and Severity of Severe Acute Respiratory Syndrome Coronavirus 2 Infection. J Am Heart Assoc. 2020 Apr 7;9(7):e016219. | CrossRef | PubMed |

Vaduganathan M, Vardeny O, Michel T, McMurray JJV, Pfeffer MA, Solomon SD. Renin-Angiotensin-Aldosterone System Inhibitors in Patients with Covid-19. N Engl J Med. 2020 Apr 23;382(17):1653-1659. | CrossRef | PubMed |

de Simone G, Mancusi C. Speculation is not evidence: antihypertensive therapy and COVID-19. Eur Heart J Cardiovasc Pharmacother. 2020 Jul 1;6(3):133-134. | CrossRef | PubMed |

Kuba K, Imai Y, Rao S, Gao H, Guo F, Guan B, et al. A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury. Nat Med. 2005 Aug;11(8):875-9. | CrossRef | PubMed |

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