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. 2021 Apr 20;34(4):339-347.
doi: 10.1093/ajh/hpaa168.

Renin-Angiotensin-Aldosterone System Inhibitors and COVID-19 Infection or Hospitalization: A Cohort Study

Sascha Dublin  1   2 , Rod L Walker  1 , James S Floyd  1   2   3 , Susan M Shortreed  1   4 , Sharon Fuller  1 , Ladia Albertson-Junkans  1 , Laura B Harrington  1   2 , Mikael Anne Greenwood-Hickman  1 , Beverly B Green  1 , Bruce M Psaty  2   3   5
Affiliations

Renin-Angiotensin-Aldosterone System Inhibitors and COVID-19 Infection or Hospitalization: A Cohort Study

Sascha Dublin et al. Am J Hypertens. .

Abstract

Background: Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may increase the risk of coronavirus disease 2019 (COVID-19) infection or affect disease severity. Prior studies have not examined risks by medication dose.

Methods: This retrospective cohort study included people aged ≥18 years enrolled in a US integrated healthcare system for at least 4 months as of 2/29/2020. Current ACEI and ARB use was identified from pharmacy data, and the estimated daily dose was calculated and standardized across medications. COVID-19 infections and hospitalizations were identified through 6/14/2020 from laboratory and hospitalization data. We used logistic regression to estimate odds ratios (ORs) and 95% confidence intervals (CIs), adjusting for race/ethnicity, obesity, and other covariates.

Results: Among 322,044 individuals, 826 developed COVID-19 infection. Among people using ACEI/ARBs, 204/56,105 developed COVID-19 (3.6 per 1,000 individuals) compared with 622/265,939 without ACEI/ARB use (2.3 per 1,000), yielding an adjusted OR of 0.91 (95% CI 0.74-1.12). For use of <1 defined daily dose (DDD) vs. nonuse, the adjusted OR for infection was 0.92 (95% CI 0.66-1.28); for 1 to <2 DDDs, 0.89 (95% CI 0.66-1.19); and for ≥2 DDDs, 0.92 (95% CI 0.72-1.18). The OR was similar for ACEIs and ARBs and in subgroups by age and sex. 26% of people with COVID-19 infection were hospitalized; the adjusted OR for hospitalization in relation to ACEI/ARB use was 0.98 (95% CI 0.63-1.54), and there was no association with dose.

Conclusions: These findings support current recommendations that individuals on these medications continue their use.

Keywords: COVID-19; angiotensin receptor blocker; angiotensin-converting enzyme inhibitor; blood pressure; coronavirus; hospitalization; hypertension; infection.

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Figures

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Graphical abstract
Figure 1.
Figure 1.
Selection of the study cohort.
Figure 2.
Figure 2.
Odds of COVID-19 infection in relation to use of RAAS inhibitors. Estimates are adjusted for age, sex, race/ethnicity, diabetes, hypertension, HF, prior MI, asthma, COPD, current tobacco use, renal disease, malignancy, Charlson comorbidity score, BMI, and use of insulin, loop diuretics, and prednisone. Abbreviations: ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; BMI, body mass index; CCB, calcium channel blocker; CI, confidence interval; COPD, chronic obstructive pulmonary disease; COVID-19, coronavirus disease 2019; DDD, defined daily dose; HF, heart failure; HTN, hypertension; MI, myocardial infarction; OR, adjusted odds ratio; RAAS, renin–angiotensin–aldosterone system.
Figure 3.
Figure 3.
Odds of COVID-19 hospitalization in relation to use of RAAS inhibitors, among individuals with COVID-19 infection. Estimates are adjusted for age, sex, race/ethnicity, diabetes, hypertension, HF, prior MI, asthma or COPD, and Charlson comorbidity score. Abbreviations: ACEI, angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; CCB, calcium channel blocker; CI, confidence interval; COPD, chronic obstructive pulmonary disease; COVID-19, coronavirus disease 2019; DDD, defined daily dose; HF, heart failure; MI, myocardial infarction; OR, adjusted odds ratio; RAAS, renin–angiotensin–aldosterone system.
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