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Use of renin-angiotensin-aldosterone system inhibitors and risk of COVID-19 requiring admission to hospital: a case-population study.
Lancet. 2020 05 30; 395(10238):1705-1714.Lct

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 PCR-confirmed 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 11 390 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.

FUNDING

Instituto de Salud Carlos III.

Authors+Show Affiliations

Clinical Pharmacology Unit, University Hospital Príncipe de Asturias, Alcalá de Henares, Madrid, Spain; Department of Biomedical Sciences (Pharmacology Section), University of Alcalá (IRYCIS), Alcalá de Henares, Madrid, Spain. Electronic address: francisco.abajo@uah.es.Clinical Pharmacology Unit, University Hospital Príncipe de Asturias, Alcalá de Henares, Madrid, Spain; Department of Biomedical Sciences (Pharmacology Section), University of Alcalá (IRYCIS), Alcalá de Henares, Madrid, Spain.Clinical Pharmacology Unit, University Hospital Príncipe de Asturias, Alcalá de Henares, Madrid, Spain.Clinical Pharmacology Department, University Hospital La Princesa, Teófilo Hernando Institute, Autonomous University of Madrid, Institute of Health La Princesa, Madrid, Spain.Clinical Pharmacology Unit, University Hospital Ramón y Cajal (IRYCIS), Madrid, Spain.Department of Biomedical Sciences (Pharmacology Section), University of Alcalá (IRYCIS), Alcalá de Henares, Madrid, Spain; Department of Clinical Pharmacology, Defense Central Hospital, Madrid, Spain.Department of Clinical Pharmacology, Clinic Hospital San Carlos, Department of Pharmacology and Toxicology, Complutense University of Madrid (IdISSC), Madrid, Spain.Centre of Network Biomedical Research on Frailty and Healthy Ageing (CIBERFES), Institute of Health Carlos III, Madrid, Spain.Clinical Pharmacology Department, University Hospital Puerta de Hierro, Majadahonda, Madrid, Spain.Clinical Pharmacology Unit, University Hospital Ramón y Cajal (IRYCIS), Madrid, Spain.Department of Biomedical Sciences (Pharmacology Section), University of Alcalá (IRYCIS), Alcalá de Henares, Madrid, Spain; Department of Clinical Pharmacology, Defense Central Hospital, Madrid, Spain.Department of Clinical Pharmacology, Clinic Hospital San Carlos, Department of Pharmacology and Toxicology, Complutense University of Madrid (IdISSC), Madrid, Spain.Institute of Biomedical Research, University Hospital of Getafe, Getafe, Madrid, Spain.Clinical Pharmacology Unit, University Hospital Ramón y Cajal (IRYCIS), Madrid, Spain.Clinical Pharmacology Department, University Hospital La Princesa, Teófilo Hernando Institute, Autonomous University of Madrid, Institute of Health La Princesa, Madrid, Spain.Geriatric Department, University Hospital of Getafe, Getafe, Madrid, Spain; Centre of Network Biomedical Research on Frailty and Healthy Ageing (CIBERFES), Institute of Health Carlos III, Madrid, Spain.Division of Pharmacoepidemiology and Pharmacovigilance, Spanish Agency for Medicines and Medical Devices, Madrid, Spain.Institute of Environmental Assessment and Water Research (IDAEA), Spanish Council for Scientific Research (CSIC), Barcelona, Spain.Clinical Pharmacology Unit, University Hospital Príncipe de Asturias, Alcalá de Henares, Madrid, Spain; Department of Biomedical Sciences (Pharmacology Section), University of Alcalá (IRYCIS), Alcalá de Henares, Madrid, Spain.Department of Nephrology, University Hospital Príncipe de Asturias, Alcalá de Henares, Madrid, Spain; Department of Medicine, University of Alcalá (IRYCIS), Alcalá de Henares, Madrid, Spain.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32416785

Citation

de Abajo, Francisco J., et al. "Use of Renin-angiotensin-aldosterone System Inhibitors and Risk of COVID-19 Requiring Admission to Hospital: a Case-population Study." Lancet (London, England), vol. 395, no. 10238, 2020, pp. 1705-1714.
de Abajo FJ, Rodríguez-Martín S, Lerma V, et al. Use of renin-angiotensin-aldosterone system inhibitors and risk of COVID-19 requiring admission to hospital: a case-population study. Lancet. 2020;395(10238):1705-1714.
de Abajo, F. J., Rodríguez-Martín, S., Lerma, V., Mejía-Abril, G., Aguilar, M., García-Luque, A., Laredo, L., Laosa, O., Centeno-Soto, G. A., Ángeles Gálvez, M., Puerro, M., González-Rojano, E., Pedraza, L., de Pablo, I., Abad-Santos, F., Rodríguez-Mañas, L., Gil, M., Tobías, A., Rodríguez-Miguel, A., & Rodríguez-Puyol, D. (2020). Use of renin-angiotensin-aldosterone system inhibitors and risk of COVID-19 requiring admission to hospital: a case-population study. Lancet (London, England), 395(10238), 1705-1714. https://doi.org/10.1016/S0140-6736(20)31030-8
de Abajo FJ, et al. Use of Renin-angiotensin-aldosterone System Inhibitors and Risk of COVID-19 Requiring Admission to Hospital: a Case-population Study. Lancet. 2020 05 30;395(10238):1705-1714. PubMed PMID: 32416785.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Use of renin-angiotensin-aldosterone system inhibitors and risk of COVID-19 requiring admission to hospital: a case-population study. AU - de Abajo,Francisco J, AU - Rodríguez-Martín,Sara, AU - Lerma,Victoria, AU - Mejía-Abril,Gina, AU - Aguilar,Mónica, AU - García-Luque,Amelia, AU - Laredo,Leonor, AU - Laosa,Olga, AU - Centeno-Soto,Gustavo A, AU - Ángeles Gálvez,Maria, AU - Puerro,Miguel, AU - González-Rojano,Esperanza, AU - Pedraza,Laura, AU - de Pablo,Itziar, AU - Abad-Santos,Francisco, AU - Rodríguez-Mañas,Leocadio, AU - Gil,Miguel, AU - Tobías,Aurelio, AU - Rodríguez-Miguel,Antonio, AU - Rodríguez-Puyol,Diego, AU - ,, Y1 - 2020/05/14/ PY - 2020/04/17/received PY - 2020/04/27/revised PY - 2020/04/29/accepted PY - 2020/5/18/pubmed PY - 2020/6/3/medline PY - 2020/5/18/entrez SP - 1705 EP - 1714 JF - Lancet (London, England) JO - Lancet VL - 395 IS - 10238 N2 - 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 PCR-confirmed 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 11 390 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. FUNDING: Instituto de Salud Carlos III. SN - 1474-547X UR - https://www.unboundmedicine.com/medline/citation/32416785/Use_of_renin_angiotensin_aldosterone_system_inhibitors_and_risk_of_COVID_19_requiring_admission_to_hospital:_a_case_population_study_ DB - PRIME DP - Unbound Medicine ER -