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. 2021 May;289(5):688-699.
doi: 10.1111/joim.13202. Epub 2020 Dec 6.

ACE inhibitors, angiotensin receptor blockers and endothelial injury in COVID-19

S Tetlow  1 , A Segiet-Swiecicka  2   3 , R O'Sullivan  4 , S O'Halloran  4 , K Kalb  4 , C Brathwaite-Shirley  4 , L Alger  4 , A Ankuli  4 , M S Baig  4 , F Catmur  4 , T Chan  4 , D Dudley  4 , J Fisher  4 , M U Iqbal  4 , J Puczynska  4 , R Wilkins  4 , R Bygate  5 , P Roberts  4
Affiliations

ACE inhibitors, angiotensin receptor blockers and endothelial injury in COVID-19

S Tetlow et al. J Intern Med. 2021 May.

Abstract

Background: COVID-19 is caused by the coronavirus SARS-CoV-2, which uses angiotensin-converting enzyme 2 (ACE-2) as a receptor for cellular entry. It is theorized that ACE inhibitors (ACE-Is) or angiotensin receptor blockers (ARBs) may increase vulnerability to SARS-CoV-2 by upregulating ACE-2 expression, but ACE-I/ARB discontinuation is associated with clinical deterioration.

Objective: To determine whether ACE-I and ARB use is associated with acute kidney injury (AKI), macrovascular thrombosis and in-hospital mortality.

Methods: A retrospective, single-centre study of 558 hospital inpatients with confirmed COVID-19 admitted from 1 March to 30 April 2020, followed up until 24 May 2020. AKI and macrovascular thrombosis were primary end-points, and in-hospital mortality was a secondary end-point.

Results: AKI occurred in 126 (23.1%) patients, 34 (6.1%) developed macrovascular thrombi, and 200 (35.9%) died. Overlap propensity score-weighted analysis showed no significant effect of ACE-I/ARB use on the risk of occurrence of the specified end-points. On exploratory analysis, severe chronic kidney disease (CKD) increases odds of macrovascular thrombi (OR: 8.237, 95% CI: 1.689-40.181, P = 0.009). The risk of AKI increased with advancing age (OR: 1.028, 95% CI: 1.011-1.044, P = 0.001) and diabetes (OR: 1.675, 95% CI: 1.065-2.633, P = 0.025). Immunosuppression was associated with lower risk of AKI (OR: 0.160, 95% CI: 0.029-0.886, P = 0.036). Advancing age, dependence on care, male gender and eGFR < 60 mL min-1 /1.73 m2 increased odds of in-hospital mortality.

Conclusion: We did not identify an association between ACE-I/ARB use and AKI, macrovascular thrombi or mortality. This supports the recommendations of the European and American Societies of Cardiology that ACE-Is and ARBs should not be discontinued during the COVID-19 pandemic.

Keywords: ACE inhibitors; critical care; endothelial function; infectious disease; renal failure; thrombosis.

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Conflict of interest statement

The authors have no conflicts of interest to declare.

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