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Do ACE inhibitors and angiotensin receptor antagonists increase the risk of severe COVID-19?

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NORWEGIAN
Anne Hege Aamodt, Marte H. Bjørk, Erling A. Tronvik, Eirik Alnes Buanes, Lars Jacob Stovner, Dan Atar About the authors
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Anne Hege Aamodt

E-mail: a.h.aamodt@medisin.uio.no

Anne Hege Aamodt is a specialist in neurology and senior consultant in the Department of Neurology, Oslo University Hospital. She is president of the Norwegian Neurological Association.

The author has completed the ICMJE form and declares no conflicts of interest.

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Marte H. Bjørk

Marte H. Bjørk is a senior consultant in the Department of Neurology, Haukeland University Hospital, and associate professor in the Department of Clinical Medicine, University of Bergen.

The author has completed the ICMJE form and declares no conflicts of interest.

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Erling A. Tronvik

Erling A. Tronvik is a senior consultant in the Department of Neurology and Clinical Neurophysiology, St. Olavs Hospital, Trondheim University Hospital, and a professor in the Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology.

The author has completed the ICMJE form and declares no conflicts of interest.

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Eirik Alnes Buanes

Eirik Alnes Buanes is a senior consultant in the Department of Intensive Care, Haukeland University Hospital, and is in charge of the Norwegian Intensive Care and Pandemic Registry.

The author has completed the ICMJE form and declares no conflicts of interest.

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Lars Jacob Stovner

Lars Jacob Stovner is head of the Norwegian National Headache Centre in the Department of Neurology and Clinical Neurophysiology, St. Olavs Hospital, Trondheim University Hospital, and a professor in the Department of Neuromedicine and Movement Science, Norwegian University of Science and Technology.

The author has completed the ICMJE form and declares no conflicts of interest.

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Dan Atar

Dan Atar is a specialist in cardiology and internal medicine, senior consultant in the Department of Cardiology, Oslo University Hospital, head of research in the Division of Medicine, Oslo University Hospital, and professor at the Institute of Clinical Medicine, University of Oslo.

The author has completed the ICMJE form and declares no conflicts of interest.

Artikkel

Hypertension and diabetes mellitus are risk factors for a severe course of COVID-19. Questions have been raised as to whether this association is related to the use of ACE inhibitors and angiotensin II receptor blockers.

People with hypertension and diabetes mellitus are more prone to a severe course of illness should they contract COVID-19 (1). Clinical data and understanding of the cellular mechanisms of COVID-19 have raised the question of whether this correlation is related to the use of angiotensin-converting enzyme inhibitors (ACE inhibitors) and angiotensin II receptor blockers (AII receptor blockers, also known as ARBs), since these drugs may in principle affect the pathophysiology of COVID-19 (2, 3).

ACE inhibitors and AII receptor blockers are used by around 14 % of the population of the Nordic countries, mainly for hypertension and heart failure as well as for migraine prophylaxis (4). The SARS-CoV-2 virus enters its target cell by binding to the angiotensin-converting enzyme 2 (ACE2) receptor on the cell surface (5), and increased expression of ACE2 can facilitate infection with SARS-CoV (6). As ACE inhibitors and AII receptor blockers increase the expression of ACE2 (7), some have advised caution in the use of these drugs (8). However, the European Society of Cardiology (ESC) and several other international professional associations have recommended that they not be discontinued (9), as discontinuation has been shown to increase the risk of complications and mortality (10). Recent studies published in The New England Journal of Medicine support the latter recommendations.

New studies on COVID-19 and the use of antihypertensive drugs

In a new population-based case-control study from Lombardy in Italy, 6 272 patients with COVID-19 were compared with 30 759 control subjects (11). The average age was 68 years, and 37 % were women. Although a higher proportion of individuals in the COVID-19 group were receiving antihypertensive treatment (including ACE inhibitors and AII receptor blockers) than in the control group, there was no association between use of these drugs and COVID-19. Subgroup analyses also revealed no association between severe or fatal cases of COVID-19 and the use of ACE inhibitors or AII receptor blockers (11).

There are no grounds for changing prescribing practices or the use of ACE inhibitors and angiotensin II receptor blockers during the coronavirus pandemic

A study with clinical data from a total of 8 910 patients with COVID-19 from 169 hospitals in Asia, Europe and North America found that 515 (5.8 %) of the patients died while in hospital (12). Factors associated with mortality were age over 65, coronary artery disease, heart failure, arrhythmias, COPD and smoking. Neither the use of ACE inhibitors nor of AII receptor blockers was associated with mortality.

An observational study that included the review of medical records of 12 594 patients tested for COVID-19 in New York also showed no association between the results of the tests and the use of antihypertensive drugs (13).

These three studies provide important information on COVID-19 and the use of antihypertensive drugs, and indicate that the increased vulnerability of people with hypertension and diabetes mellitus is due to factors other than the use of specific types of antihypertensives. There is thus no definitive evidence to date that the use of ACE inhibitors or AII receptor blockers entails an increased risk of a severe course of COVID-19. The results of these studies support the advice issued by the ESC. There are no grounds for changing prescribing practices or the use of ACE inhibitors or AII receptor blockers during the coronavirus pandemic.

Published: 11 June 2020
Tidsskr Nor Legeforen 2020
doi: 10.4045/tidsskr.20.0411

Received 5.5.2020, first revision submitted 8.5.2020, accepted 13.5.2020.

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