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Hippisley-Cox J, Young D, Coupland C, et al. Risk of severe COVID-19 disease with ACE inhibitors and angiotensin receptor blockers: cohort study including 8.3 million people. Heart. 2020 Oct;106(19):1503-1511. doi: 10.1136/heartjnl-2020-317393. Epub 2020 Jul 31. (Original study)
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.


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Ratings
Discipline Area Score
Family Medicine (FM)/General Practice (GP) 6 / 7
General Internal Medicine-Primary Care(US) 6 / 7
Infectious Disease 6 / 7
Respirology/Pulmonology 6 / 7
Hospital Doctor/Hospitalists 6 / 7
Internal Medicine 6 / 7
Intensivist/Critical Care 6 / 7
Comments from MORE raters

Intensivist/Critical Care rater

As an ICU physician, I find these results are of interest but don’t really guide clinical management. Most clinicians will continue or hold ACEI/ARB as otherwise clinically indicated irrespective of COVID-19. These results don’t inform decision-making, though they are reassuring for individuals already on these medications.

Intensivist/Critical Care rater

This is a good study with important information. It has the limitations of observational cohort studies and potential unmeasured confounders. HOwever, overall at least, it is useful to direct providers to guide patients that they likely do not need to stop their ACE-inhibitors or ARBs.

Intensivist/Critical Care rater

This is newsworthy, interesting and hypothesis generating. There will be risks looking at this in the future.
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