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  • SARS-CoV-2 infection and adverse outcomes in users of ACE inhibitors and angiotensin-receptor blockers: a nationwide case-control and cohort analysis

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Respiratory infection
Original research
SARS-CoV-2 infection and adverse outcomes in users of ACE inhibitors and angiotensin-receptor blockers: a nationwide case-control and cohort analysis
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  1. Christian Fynbo Christiansen1,
  2. Anton Pottegård2,
  3. Uffe Heide-Jørgensen1,
  4. Jacob Bodilsen3,
  5. Ole Schmeltz Søgaard4,
  6. Michael Maeng5,
  7. Simon Tilma Vistisen6,7,
  8. Morten Schmidt1,5,8,
  9. Lars Christian Lund2,
  10. Mette Reilev2,
  11. Jesper Hallas2,
  12. Marianne Voldstedlund9,
  13. Anders Husby10,
  14. Marianne Kragh Thomsen11,
  15. Nanna Borup Johansen12,
  16. Nikolai Constantin Brun12,
  17. Reimar Wernich Thomsen1,
  18. Hans Erik Bøtker5,
  19. Henrik Toft Sørensen1,13
  1. 1 Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, Denmark
  2. 2 Clinical Pharmacology, Pharmacy and Environmental Medicine, Department of Public Health, University of Southern Denmark, Odense C, Denmark
  3. 3 Department of Infectious Diseases, Aalborg University Hospital, Aalborg, Denmark
  4. 4 Department of Infectious Diseases, Aarhus University Hospital, Aarhus N, Denmark
  5. 5 Department of Cardiology, Aarhus University Hospital, Aarhus N, Denmark
  6. 6 Department of Clinical Medicine, Aarhus University, Aarhus N, Denmark
  7. 7 Department of Intensive Care, Aarhus University Hospital, Aarhus N, Denmark
  8. 8 Department of Cardiology, Regional Hospital West Jutland, Herning, Denmark
  9. 9 Department of Data Integration and Analysis, Statens Serum Institut, Copenhagen S, Denmark
  10. 10 Department of Epidemiology Research, Statens Serum Institut, Copenhagen S, Denmark
  11. 11 Department of Clinical Microbiology, Aarhus University Hospital, Aarhus N, Denmark
  12. 12 Department of Medical Evaluation and Biostatistics, Danish Medicines Agency, Copenhagen S, Denmark
  13. 13 Center for Population Health Sciences, Stanford University, Stanford, California, USA
  1. Correspondence to Dr Christian Fynbo Christiansen, Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus N, Denmark; cfc{at}clin.au.dk

Abstract

Objective To examine the impact of ACE inhibitor (ACE-I)/angiotensin receptor blocker (ARB) use on rate of SARS-CoV-2 infection and adverse outcomes.

Methods This nationwide case-control and cohort study included all individuals in Denmark tested for SARS-CoV-2 RNA with PCR from 27 February 2020 to 26 July 2020. We estimated confounder-adjusted ORs for a positive test among all SARS-CoV-2 tested, and inverse probability of treatment weighted 30-day risk and risk ratios (RRs) of hospitalisation, intensive care unit (ICU) admission and mortality comparing current ACE-I/ARB use with calcium channel blocker (CCB) use and with non-use.

Results The study included 13 501 SARS-CoV-2 PCR-positive and 1 088 695 PCR-negative individuals. Users of ACE-I/ARB had a marginally increased rate of a positive PCR when compared with CCB users (aOR 1.17, 95% CI 1.00 to 1.37), but not when compared with non-users (aOR 1.00 95% CI 0.92 to 1.09).

Among PCR-positive individuals, 1466 (11%) were ACE-I/ARB users. The weighted risk of hospitalisation was 36.5% in ACE-I/ARB users and 43.3% in CCB users (RR 0.84, 95% CI 0.70 to 1.02). The risk of ICU admission was 6.3% in ACE-I/ARB users and 5.4% in CCB users (RR 1.17, 95% CI 0.64 to 2.16), while the 30-day mortality was 12.3% in ACE-I/ARB users and 13.9% in CCB users (RR 0.89, 95% CI 0.61 to 1.30). The associations were similar when ACE-I/ARB users were compared with non-users.

Conclusions ACE-I/ARB use was associated neither with a consistently increased rate nor with adverse outcomes of SARS-CoV-2 infection. Our findings support the current recommendation of continuing use of ACE-Is/ARBs during the SARS-CoV-2 pandemic.

Trial registration number EUPAS34887

  • clinical epidemiology
  • critical care
  • viral infection
  • respiratory infection

This article is made freely available for use in accordance with BMJ’s website terms and conditions for the duration of the covid-19 pandemic or until otherwise determined by BMJ. You may use, download and print the article for any lawful, non-commercial purpose (including text and data mining) provided that all copyright notices and trade marks are retained.

https://bmj.com/coronavirus/usage

https://doi.org/10.1136/thoraxjnl-2020-215768

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    Footnotes

    • Twitter @ChristianFynbo, @dr_rwt

    • Correction notice This article has been corrected since it was published Online First. An author first name and last name were interchanged.

    • Contributors CFC, UH-J, AP, RWT and HTS planned and designed the study. All authors contributed with input to the design and participated in the interpretation of the data. CFC reviewed the literature, organised the writing and wrote the initial manuscript. All authors critically reviewed the manuscript and approved the final version for submission. AP and LCL conducted the statistical analyses. AP and HTS obtained funding. NCB, HTS, RWT supervised the study. AP and HTS are the guarantors. The corresponding author attests that all listed authors meet authorship criteria and that no others meeting the criteria have been omitted.

    • Funding The study was funded by Aarhus University and the University of Southern Denmark.

    • Competing interests CFC, UH-J, RWT and HTS have not received any personal fees, grants, travel grants or teaching grants from companies, but the Department of Clinical Epidemiology is involved in studies with funding from various companies as research grants to (and administered by) Aarhus University. MR, LCL, AP and JH have participated in industry-funded projects with money paid to their employer, the University of Southern Denmark. MM has received speaker or advisory board fees from AstraZeneca, Bayer, Boston Scientific, Boehringer-Ingelheim, Bristol-Myers Squibb, and Novo Nordisk.

    • Patient consent for publication Not required.

    • Ethics approval The study was registered at the University of Southern Denmark (record no. 10.960) and approved by the Danish Health Data Authority (FSEID-00004874). According to Danish law, registry-based studies do not require approval from ethics committees or informed consent from participants.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Data availability statement Data may be obtained from a third party and are not publicly available. No additional data available. Because of the sensitive nature of the data collected for this study, requests to access the databases used in this study from researchers at certified Danish research institutions may be sent to the Danish Health Data Authority by email to forskerservice@sundhedsdata.dk.