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

Hippisley-Cox, Julia; Young, Duncan; Coupland, Carol; Channon, Keith M.; Tan, Pui San; Harrison, David A.; Rowan, Kathryn; Aveyard, Paul; Pavord, Ian D.; Watkinson, Peter J.

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.

• Journal Article Type: Article
• Acceptance Date: Jul 13, 2020
• Online Publication Date: Jul 31, 2020
• Publication Date: 2020-10
• Deposit Date: Aug 5, 2020
• Publicly Available Date: Aug 7, 2020
• Journal: Heart
• Print ISSN: 1355-6037
• Electronic ISSN: 1468-201X
• Publisher: BMJ Publishing Group
• Peer Reviewed: Peer Reviewed
• Volume: 106
• Issue: 19
• Pages: 1503-1511
• DOI: https://doi.org/10.1136/heartjnl-2020-317393
• Keywords: Cardiology and Cardiovascular Medicine
• Public URL: https://nottingham-repository.worktribe.com/output/4812470
• Publisher URL: https://heart.bmj.com/content/early/2020/07/31/heartjnl-2020-317393