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Renin-angiotensin system inhibitors effect before and during hospitalization in COVID-19 outcomes: Final analysis of the international HOPE COVID-19 (Health Outcome Predictive Evaluation for COVID-19) registry - 26/05/21

Doi : 10.1016/j.ahj.2021.04.001 
Iván J. Núñez-Gil, MD, PhD a, , Iván Olier, PhD b, Gisela Feltes, MD c, María C. Viana-Llamas, MD d, Charbel Maroun-Eid, MD e, Rodolfo Romero, MD, PhD f, Inmaculada Fernández-Rozas, MD g, Aitor Uribarri, MD, PhD h, Victor M. Becerra-Muñoz, MD i, Emilio Alfonso-Rodriguez, MD j, Marcos García-Aguado, MD k, Javier Elola, MD, PhD l, Alex Castro-Mejía, MD m, Martino Pepe, MD, PhD n, Juan Fortunato Garcia-Prieto, MD o, Adelina Gonzalez, MD p, Fabrizio Ugo, MD, PhD q, Enrico Cerrato, MD, PhD r, Elvira Bondia, MD s, Sergio Raposeiras-Roubin, MD, PhD t, Jorge L. Jativa Mendez, MD, PhD u, Carolina Espejo, MD v, Álvaro López-Masjuan, MD w, Francisco Marin, MD, PhD x, Javier López-Pais, MD y, Mohammad Abumayyaleh, MD, PhD z, Miguel Corbi-Pascual, MD, PhD aa, Christoph Liebetrau, MD, PhD bb, Harish Ramakrishna, MD, FACC, FESC cc, Vicente Estrada, MD, PhD a, Carlos Macaya, MD, PhD a, Antonio Fernandez-Ortiz, MD, PhD a
On behalf of

HOPE COVID-19 Investigators (Cols Appendix)

a Hospital Clínico San Carlos, Universidad Complutense de Madrid, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain 
b Liverpool Centre for Cardiovascular Science, Liverpool John Moores University, Liverpool, United Kingdom 
c Hospital Nuestra Señora de América, Madrid, Spain 
d Hospital Universitario Guadalajara, Guadalajara, Spain 
e Hospital Universitario La Paz, Instituto de Investigación Hospital Universitario La Paz (IdiPAZ), Madrid, Spain 
f Hospital Universitario Getafe, Universidad Europea de Madrid, Madrid, Spain 
g Hospital Severo Ochoa, Leganés, Spain 
h Hospital Clínico Universitario de Valladolid, Valladolid, Spain 
i Unidad de Gestión Clínica Área del Corazón, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Universidad de Málaga (UMA), Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV), Málaga, Spain 
j Instituto de Cardiología y Cirugía Cardiovascular, Havana, Cuba 
k Hospital Puerta de Hierro, Madrid, Spain 
l Instituto para la Mejora de la Asistencia Sanitaria, IMAS, Madrid, Spain 
m Hospital General del norte de Guayaquil IESS Los Ceibos, Guayaquil, Ecuador 
n Azienda ospedaliero-universitaria consorziale policlinico di Bari, Bari, Italy 
o Hospital de Manises, Valencia, Spain 
p Hospital Universitario Infanta Sofia, San Sebastian de los Reyes, Madrid, Spain 
q Sant'Andrea Hospital, Vercelli, Italy 
r San Luigi Gonzaga University Hospital, Orbassano and Rivoli Infermi Hospital, Rivoli (Turin), Italy 
s Hospital Clínico Universitario, Incliva, Universidad de Valencia, Valencia, Spain 
t Hospital Universitario Álvaro Cunqueiro, Instituto de Investigación Sanitaria Galicia Sur, Vigo, Spain 
u Hospital de especialidades de las Fuerzas Armadas, Quito, Ecuador 
v Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Spain 
w Hospital Universitario Juan Ramón Jiménez, Huelva, Spain 
x Hospital Clínico Universitario Virgen de la Arrixaca, IMIB-Arrixaca, Universidad de Murcia, CIBERCV, Murcia, Spain 
y Complejo Hospitalario Universitario de Santiago de Compostela, Santiago, Spain 
z University Medical Center Mannheim (UMM), University of Heidelberg, Mannheim, Germany 
aa Hospital General de Albacete, Albacete, Spain 
bb Kerckhoff Heart and Thorax Center, Bad Nauheim, Germany 
cc Mayo Clinic, Rochester, MN 

Reprint requests: Iván J. Núñez-Gil, MD, PhD, MSc, Hospital Clínico San Carlos, Prof Martin Lagos St. 28040, Madrid, SpainHospital Clínico San CarlosProf Martin Lagos St. 28040MadridSpain

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ABSTRACT

Background

The use of Renin-Angiotensin system inhibitors (RASi) in patients with coronavirus disease 2019 (COVID-19) has been questioned because both share a target receptor site.

Methods

HOPE-COVID-19 (NCT04334291) is an international investigator-initiated registry. Patients are eligible when discharged after an in-hospital stay with COVID-19, dead or alive. Here, we analyze the impact of previous and continued in-hospital treatment with RASi in all-cause mortality and the development of in-stay complications.

Results

We included 6503 patients, over 18 years, from Spain and Italy with data on their RASi status. Of those, 36.8% were receiving any RASi before admission. RASi patients were older, more frequently male, with more comorbidities and frailer. Their probability of death and ICU admission was higher. However, after adjustment, these differences disappeared. Regarding RASi in-hospital use, those who continued the treatment were younger, with balanced comorbidities but with less severe COVID19. Raw mortality and secondary events were less frequent in RASi. After adjustment, patients receiving RASi still presented significantly better outcomes, with less mortality, ICU admissions, respiratory insufficiency, need for mechanical ventilation or prone, sepsis, SIRS and renal failure (p<0.05 for all). However, we did not find differences regarding the hospital use of RASi and the development of heart failure.

Conclusion

RASi historic use, at admission, is not related to an adjusted worse prognosis in hospitalized COVID-19 patients, although it points out a high-risk population. In this setting, the in-hospital prescription of RASi is associated with improved survival and fewer short-term complications.

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 Trial Numbers: NCT04334291/ EUPAS34399.


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