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Association of Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Use With COVID-19 Diagnosis and Mortality.
JAMA. 2020 Jul 14; 324(2):168-177.JAMA

Abstract

Importance

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.

Objective

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.

Exposures

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.

Results

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.

Authors+Show Affiliations

The Heart Center, University Hospital of Copenhagen, Rigshospitalet, Copenhagen, Denmark.The Heart Center, University Hospital of Copenhagen, Rigshospitalet, Copenhagen, Denmark.The Heart Center, University Hospital of Copenhagen, Rigshospitalet, Copenhagen, Denmark.Section of Cardiovascular Medicine, Department of Medicine, Boston Medical Center, Boston University School of Medicine, Boston, Massachusetts.Department of Endocrinology, Bispebjerg and Frederiksberg Hospital, Copenhagen, Denmark.Department of Cardiology, Aalborg University Hospital, Aalborg, Denmark.Department of Cardiology, Copenhagen University Hospital Herlev and Gentofte, Hellerup, Denmark.Department of Cardiovascular Epidemiology and Research, The Danish Heart Foundation, Copenhagen, Denmark.Department of Cardiology, Copenhagen University Hospital Herlev and Gentofte, Hellerup, Denmark. Department of Cardiovascular Epidemiology and Research, The Danish Heart Foundation, Copenhagen, Denmark.Department of Cardiovascular Epidemiology and Research, The Danish Heart Foundation, Copenhagen, Denmark.Department of Clinical Epidemiology and Department of Cardiology, Hillerød Hospital, Hillerød, Denmark.The Heart Center, University Hospital of Copenhagen, Rigshospitalet, Copenhagen, Denmark.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32558877

Citation

Fosbøl, Emil L., et al. "Association of Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Use With COVID-19 Diagnosis and Mortality." JAMA, vol. 324, no. 2, 2020, pp. 168-177.
Fosbøl EL, Butt JH, Østergaard L, et al. Association of Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Use With COVID-19 Diagnosis and Mortality. JAMA. 2020;324(2):168-177.
Fosbøl, E. L., Butt, J. H., Østergaard, L., Andersson, C., Selmer, C., Kragholm, K., Schou, M., Phelps, M., Gislason, G. H., Gerds, T. A., Torp-Pedersen, C., & Køber, L. (2020). Association of Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Use With COVID-19 Diagnosis and Mortality. JAMA, 324(2), 168-177. https://doi.org/10.1001/jama.2020.11301
Fosbøl EL, et al. Association of Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Use With COVID-19 Diagnosis and Mortality. JAMA. 2020 Jul 14;324(2):168-177. PubMed PMID: 32558877.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Association of Angiotensin-Converting Enzyme Inhibitor or Angiotensin Receptor Blocker Use With COVID-19 Diagnosis and Mortality. AU - Fosbøl,Emil L, AU - Butt,Jawad H, AU - Østergaard,Lauge, AU - Andersson,Charlotte, AU - Selmer,Christian, AU - Kragholm,Kristian, AU - Schou,Morten, AU - Phelps,Matthew, AU - Gislason,Gunnar H, AU - Gerds,Thomas A, AU - Torp-Pedersen,Christian, AU - Køber,Lars, PY - 2020/6/20/pubmed PY - 2020/9/22/medline PY - 2020/6/20/entrez SP - 168 EP - 177 JF - JAMA JO - JAMA VL - 324 IS - 2 N2 - Importance: 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. Objective: 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. Exposures: 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. Results: 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. SN - 1538-3598 UR - https://www.unboundmedicine.com/medline/citation/32558877/full_citation L2 - https://jamanetwork.com/journals/jama/fullarticle/10.1001/jama.2020.11301 DB - PRIME DP - Unbound Medicine ER -