Use of renin–angiotensin–aldosterone system inhibitors and risk of COVID-19 requiring admission to hospital: a case-population study
Date
2020Author
Abajo, Francisco J de
Rodríguez-Martín, Sara
Lerma, Victoria
Mejía-Abril, Gina
Aguilar, Mónica
García-Luque, Amelia
Laredo, Leonor
Laosa, Olga
Centeno-Soto, Gustavo A
Gálvez, Maria Ángeles
Puerro, Miguel
González-Rojano, Esperanza
Pedraza, Laura
Pablo, Itziar de
Abad-Santos, Francisco
Rodríguez-Mañas, Leocadio
Gil, Miguel
Tobías, Aurelio
Rodríguez-Miguel, Antonio
Rodríguez-Puyol, Diego
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Abstract
Background Concerns have been raised about the possibility that inhibitors of the renin–angiotensin–aldosterone
system (RAAS) could predispose individuals to severe COVID-19; however, epidemiological evidence is lacking. We
report the results of a case-population study done in Madrid, Spain, since the outbreak of COVID-19.
Methods In this case-population study, we consecutively selected patients aged 18 years or older with a PCRconfirmed diagnosis of COVID-19 requiring admission to hospital from seven hospitals in Madrid, who had been
admitted between March 1 and March 24, 2020. As a reference group, we randomly sampled ten patients per case,
individually matched for age, sex, region (ie, Madrid), and date of admission to hospital (month and day; index
date), from Base de datos para la Investigación Farmacoepidemiológica en Atención Primaria (BIFAP), a Spanish
primary health-care database, in its last available year (2018). We extracted information on comorbidities and
prescriptions up to the month before index date (ie, current use) from electronic clinical records of both cases and
controls. The outcome of interest was admission to hospital of patients with COVID-19. To minimise confounding
by indication, the main analysis focused on assessing the association between COVID-19 requiring admission to
hospital and use of RAAS inhibitors compared with use of other antihypertensive drugs. We calculated odds ratios
(ORs) and 95% CIs, adjusted for age, sex, and cardiovascular comorbidities and risk factors, using conditional
logistic regression. The protocol of the study was registered in the EU electronic Register of Post-Authorisation
Studies, EUPAS34437.
Findings We collected data for 1139 cases and 11390 population controls. Among cases, 444 (39·0%) were female and
the mean age was 69·1 years (SD 15·4), and despite being matched on sex and age, a significantly higher proportion
of cases had pre-existing cardiovascular disease (OR 1·98, 95% CI 1·62–2·41) and risk factors (1·46, 1·23–1·73) than
did controls. Compared with users of other antihypertensive drugs, users of RAAS inhibitors had an adjusted OR for
COVID-19 requiring admission to hospital of 0·94 (95% CI 0·77–1·15). No increased risk was observed with either
angiotensin-converting enzyme inhibitors (adjusted OR 0·80, 0·64–1·00) or angiotensin-receptor blockers (1·10,
0·88–1·37). Sex, age, and background cardiovascular risk did not modify the adjusted OR between use of RAAS
inhibitors and COVID-19 requiring admission to hospital, whereas a decreased risk of COVID-19 requiring admission
to hospital was found among patients with diabetes who were users of RAAS inhibitors (adjusted OR 0·53, 95% CI
0·34–0·80). The adjusted ORs were similar across severity degrees of COVID-19.
Interpretation RAAS inhibitors do not increase the risk of COVID-19 requiring admission to hospital, including fatal
cases and those admitted to intensive care units, and should not be discontinued to prevent a severe case of COVID-19.
Palabras clave
System inhibitors; COVID-19Link to resource
https://doi.org/10.1016/Collections
Comments
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