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. 2020 Oct;106(19):1503-1511.
doi: 10.1136/heartjnl-2020-317393. Epub 2020 Jul 31.

Risk of severe COVID-19 disease with ACE inhibitors and angiotensin receptor blockers: cohort study including 8.3 million people

Julia Hippisley-Cox  1 , Duncan Young  2   3 , Carol Coupland  4 , Keith M Channon  5 , Pui San Tan  6 , David A Harrison  7 , Kathryn Rowan  8 , Paul Aveyard  6 , Ian D Pavord  9 , Peter J Watkinson  5   10
Affiliations

Risk of severe COVID-19 disease with ACE inhibitors and angiotensin receptor blockers: cohort study including 8.3 million people

Julia Hippisley-Cox et al. Heart. 2020 Oct.

Abstract

Background: There is uncertainty about the associations of angiotensive enzyme (ACE) inhibitor and angiotensin receptor blocker (ARB) drugs with COVID-19 disease. We studied whether patients prescribed these drugs had altered risks of contracting severe COVID-19 disease and receiving associated intensive care unit (ICU) admission.

Methods: This was a prospective cohort study using routinely collected data from 1205 general practices in England with 8.28 million participants aged 20-99 years. We used Cox proportional hazards models to derive adjusted HRs for exposure to ACE inhibitor and ARB drugs adjusted for sociodemographic factors, concurrent medications and geographical region. The primary outcomes were: (a) COVID-19 RT-PCR diagnosed disease and (b) COVID-19 disease resulting in ICU care.

Findings: Of 19 486 patients who had COVID-19 disease, 1286 received ICU care. ACE inhibitors were associated with a significantly reduced risk of COVID-19 disease (adjusted HR 0.71, 95% CI 0.67 to 0.74) but no increased risk of ICU care (adjusted HR 0.89, 95% CI 0.75 to 1.06) after adjusting for a wide range of confounders. Adjusted HRs for ARBs were 0.63 (95% CI 0.59 to 0.67) for COVID-19 disease and 1.02 (95% CI 0.83 to 1.25) for ICU care.There were significant interactions between ethnicity and ACE inhibitors and ARBs for COVID-19 disease. The risk of COVID-19 disease associated with ACE inhibitors was higher in Caribbean (adjusted HR 1.05, 95% CI 0.87 to 1.28) and Black African (adjusted HR 1.31, 95% CI 1.08 to 1.59) groups than the white group (adjusted HR 0.66, 95% CI 0.63 to 0.70). A higher risk of COVID-19 with ARBs was seen for Black African (adjusted HR 1.24, 95% CI 0.99 to 1.58) than the white (adjusted HR 0.56, 95% CI 0.52 to 0.62) group.

Interpretation: ACE inhibitors and ARBs are associated with reduced risks of COVID-19 disease after adjusting for a wide range of variables. Neither ACE inhibitors nor ARBs are associated with significantly increased risks of receiving ICU care. Variations between different ethnic groups raise the possibility of ethnic-specific effects of ACE inhibitors/ARBs on COVID-19 disease susceptibility and severity which deserves further study.

Keywords: cardiac risk factors and prevention; diabetes; epidemiology; hypertension; primary care.

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Conflict of interest statement

Competing interests: JHC reports grants from National Institute for Health Research Biomedical Research Centre, Oxford, grants from John Fell Oxford University Press Research Fund, grants from Cancer Research UK (CR-UK) grant number C5255/A18085, through the Cancer Research UK Oxford Centre, grants from the Oxford Wellcome Institutional Strategic Support Fund (204826/Z/16/Z), during the conduct of the study; personal fees and other from ClinRisk Ltd (until 2019) outside the submitted work; and JH is an unpaid director of QResearch, a not-for-profit organisation which is a partnership between the University of Oxford and EMIS Health who supply the QResearch database used for this work. PW reports grants from National Institute for Health Research Biomedical Research Centre, Oxford and the Wellcome Trust (grant number is 221514/Z/20/Z), during the conduct of the study; grants from Sensyne Health, personal fees from Sensyne Health, outside the submitted work. PST reports consulting with AstraZeneca and Duke-NUS outside the submitted work. IDP reports personal fees from AstraZeneca, personal fees from Boehringer Ingelheim, personal fees from Aerocrine, personal fees from Almirall, personal fees from Novartis, personal fees from GlaxoSmithKline, personal fees from Genentech, personal fees from Regeneron, Teva, Chiesi, Sanofi, Circassia, Knopp, grants from NIHR, outside the submitted work. DY, CC, PA, DAH, KR, KC have nothing to disclose.

Figures

Figure 1
Figure 1
The adjusted HRs along with 95% CIs for (A) the outcome of a positive COVID-19 RT-PCR test and (B) the outcome of admission to an intensive care unit (ICU), for all the variables studied based on multiple imputed data. BMI, body mass index; COPD, chronic obstructive pulmonary disease.
Figure 2
Figure 2
The adjusted HRs along with 95% CIs for (A) the outcome of a positive COVID-19 RT-PCR test and (B) the outcome of admission to an intensive care unit (ICU), for all the variables studied based on the completed case analysis. BMI, body mass index; COPD, chronic obstructive pulmonary disease.
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