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. 2020 Jun;22(6):967-974.
doi: 10.1002/ejhf.1924. Epub 2020 Jul 7.

Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are not associated with severe COVID-19 infection in a multi-site UK acute hospital trust

Daniel M Bean  1   2 , Zeljko Kraljevic  1 , Thomas Searle  1 , Rebecca Bendayan  1   3 , O'Gallagher Kevin  4   5 , Andrew Pickles  1 , Amos Folarin  1   2   6   7 , Lukasz Roguski  2   6   7 , Kawsar Noor  2   6   7 , Anthony Shek  8 , Rosita Zakeri  4   5 , Ajay M Shah  4   5 , James T H Teo  4   8 , Richard J B Dobson  1   2   3   6   7
Affiliations

Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers are not associated with severe COVID-19 infection in a multi-site UK acute hospital trust

Daniel M Bean et al. Eur J Heart Fail. 2020 Jun.

Abstract

Aims: The SARS-CoV-2 virus binds to the angiotensin-converting enzyme 2 (ACE2) receptor for cell entry. It has been suggested that angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB), which are commonly used in patients with hypertension or diabetes and may raise tissue ACE2 levels, could increase the risk of severe COVID-19 infection.

Methods and results: We evaluated this hypothesis in a consecutive cohort of 1200 acute inpatients with COVID-19 at two hospitals with a multi-ethnic catchment population in London (UK). The mean age was 68 ± 17 years (57% male) and 74% of patients had at least one comorbidity. Overall, 415 patients (34.6%) reached the primary endpoint of death or transfer to a critical care unit for organ support within 21 days of symptom onset. A total of 399 patients (33.3%) were taking ACEi or ARB. Patients on ACEi/ARB were significantly older and had more comorbidities. The odds ratio for the primary endpoint in patients on ACEi and ARB, after adjustment for age, sex and co-morbidities, was 0.63 (95% confidence interval 0.47-0.84, P < 0.01).

Conclusions: There was no evidence for increased severity of COVID-19 in hospitalised patients on chronic treatment with ACEi or ARB. A trend towards a beneficial effect of ACEi/ARB requires further evaluation in larger meta-analyses and randomised clinical trials.

Keywords: Angiotensin-converting enzyme inhibitors; COVID-19; Disease outcome; Hypertension.

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Figures

Figure 1
Figure 1
Distribution of disorders between patients achieving the primary outcome (death or critical care admission) and those not achieving it by 21 days after symptom onset. The percentage of patients that have a positive mention of a disorder in each of the two groups is shown. All diseases were extracted from free‐text using CogStack and MedCAT. Only medical concept annotations with F1 >80%, more than 10 annotated samples and present in at least 10% of either group are shown. Disease names that start “Any:” are aggregate concepts for multiple specific conditions that are used in our analysis. CKD, chronic kidney disease; COPD, chronic obstructive pulmonary disease; HTN, hypertension; IHD, ischaemic heart disease.
Figure 2
Figure 2
Kaplan–Meier curves for the primary endpoint in COVID‐19 patients on chronic treatment with angiotensin‐converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB) vs. those not on these drugs. The unadjusted odds ratio (OR) for the primary endpoint for those on ACEi/ARB was 0.83 (P = 0.16); the adjusted OR was 0.63 (P < 0.01). CI, confidence interval.
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