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Is angiotensin-converting enzyme inhibitor (ACEI)/angiotensin receptor blocker (ARB) use associated with greater susceptibility to coronavirus disease 2019 (COVID-19) and with worse outcomes after COVID-19 diagnosis?
In a retrospective cohort study of 4480 patients diagnosed as having COVID-19, prior ACEI/ARB use, compared with no use, was not significantly associated with mortality (adjusted hazard ratio, 0.83). In a nested case-control study of a cohort of 494 170 patients with hypertension, use of ACEI/ARB, compared with use of other antihypertensive medications, was not significantly associated with COVID-19 diagnosis (adjusted hazard ratio, 1.05).
Prior use of ACEI/ARB was not significantly associated with COVID-19 diagnosis or with mortality among patients diagnosed as having COVID-19.
It has been hypothesized that angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) may make patients more susceptible to coronavirus disease 2019 (COVID-19) and to worse outcomes through upregulation of the functional receptor of the virus, angiotensin-converting enzyme 2.
To examine whether use of ACEI/ARBs was associated with COVID-19 diagnosis and worse outcomes in patients with COVID-19.
Design, Setting, and Participants
To examine outcomes among patients with COVID-19, a retrospective cohort study using data from Danish national administrative registries was conducted. Patients with COVID-19 from February 22 to May 4, 2020, were identified using ICD-10 codes and followed up from day of diagnosis to outcome or end of study period (May 4, 2020). To examine susceptibility to COVID-19, a Cox regression model with a nested case-control framework was used to examine the association between use of ACEI/ARBs vs other antihypertensive drugs and the incidence rate of a COVID-19 diagnosis in a cohort of patients with hypertension from February 1 to May 4, 2020.
ACEI/ARB use was defined as prescription fillings 6 months prior to the index date.
Main Outcomes and Measures
In the retrospective cohort study, the primary outcome was death, and a secondary outcome was a composite outcome of death or severe COVID-19. In the nested case-control susceptibility analysis, the outcome was COVID-19 diagnosis.
In the retrospective cohort study, 4480 patients with COVID-19 were included (median age, 54.7 years [interquartile range, 40.9-72.0]; 47.9% men). There were 895 users (20.0%) of ACEI/ARBs and 3585 nonusers (80.0%). In the ACEI/ARB group, 18.1% died within 30 days vs 7.3% in the nonuser group, but this association was not significant after adjustment for age, sex, and medical history (adjusted hazard ratio [HR], 0.83 [95% CI, 0.67-1.03]). Death or severe COVID-19 occurred in 31.9% of ACEI/ARB users vs 14.2% of nonusers by 30 days (adjusted HR, 1.04 [95% CI, 0.89-1.23]). In the nested case-control analysis of COVID-19 susceptibility, 571 patients with COVID-19 and prior hypertension (median age, 73.9 years; 54.3% men) were compared with 5710 age- and sex-matched controls with prior hypertension but not COVID-19. Among those with COVID-19, 86.5% used ACEI/ARBs vs 85.4% of controls; ACEI/ARB use compared with other antihypertensive drugs was not significantly associated with higher incidence of COVID-19 (adjusted HR, 1.05 [95% CI, 0.80-1.36]).
Conclusions and Relevance
Prior use of ACEI/ARBs was not significantly associated with COVID-19 diagnosis among patients with hypertension or with mortality or severe disease among patients diagnosed as having COVID-19. These findings do not support discontinuation of ACEI/ARB medications that are clinically indicated in the context of the COVID-19 pandemic.
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CME Disclosure Statement: Unless noted, all individuals in control of content reported no relevant financial relationships. If applicable, all relevant financial relationships have been mitigated.
Corresponding Author: Emil L. Fosbøl, MD, PhD, The Heart Center, University Hospital of Copenhagen, Rigshospitalet, Blegdamsvej 9, 2100 KBH Ø, Copenhagen, Denmark (email@example.com).
Published Online: June 19, 2020. doi:10.1001/jama.2020.11301
Author Contributions: Drs Fosbøl and Gerds had full access to all the data in the study and take responsibility for the integrity of the data and the accuracy of the data analysis.
Concept and design: Fosbøl, Selmer, Gislason, Torp-Pedersen, Køber.
Acquisition, analysis, or interpretation of data: All authors.
Drafting of the manuscript: Fosbøl, Østergaard.
Critical revision of the manuscript for important intellectual content: Butt, Østergaard, Andersson, Selmer, Kragholm, Schou, Phelps, Gislason, Gerds, Torp-Pedersen, Køber.
Statistical analysis: Fosbøl, Østergaard, Selmer, Schou, Gislason, Gerds, Torp-Pedersen, Køber.
Administrative, technical, or material support: Fosbøl, Butt, Phelps, Gislason, Torp-Pedersen, Køber.
Supervision: Selmer, Torp-Pedersen, Køber.
Conflict of Interest Disclosures: Dr Schou reported receiving speaker fees from Novartis, Novo Nordisk, AstraZeneca, and Boehringer Ingelheim. Dr Torp-Pedersen reported receiving grants from Bayer and Novo Nordisk. Dr Køber reported receiving speaker honoraria from Novartis, AstraZeneca, and Boehringer Ingelheim. No other disclosures were reported.
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