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[Preprint]. 2020 Jul 7:2020.07.06.20120386.
doi: 10.1101/2020.07.06.20120386.

Renin-angiotensin-aldosterone system inhibitors and COVID-19 infection or hospitalization: a cohort study

Sascha Dublin  1   2 , Rod 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  1   2   3   5
Affiliations

Renin-angiotensin-aldosterone system inhibitors and COVID-19 infection or hospitalization: a cohort study

Sascha Dublin et al. medRxiv. .

Update in

Abstract

There are plausible mechanisms by which angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) may increase the risk of COVID-19 infection or affect disease severity. To examine the association between these medications and COVID-19 infection or hospitalization, we conducted a retrospective cohort study within a US integrated healthcare system. Among people aged ≥18 years enrolled in the health plan 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 were identified through 6/14/2020 from laboratory and hospitalization data. We used logistic regression to estimate adjusted odds ratios (ORs) and 95% confidence intervals. Among 322,044 individuals, 720 developed COVID-19 infection. Among people using ACEI/ARBs, 183/56,105 developed COVID-19 (3.3 per 1000 individuals) compared with 537/265,939 without ACEI/ARB use (2.0 per 1000), yielding an adjusted OR of 0.94 (95% CI 0.75-1.16). For use of < 1 defined daily dose vs. nonuse, the adjusted OR for infection was 0.89 (95% CI 0.62-1.26); for 1 to < 2 defined daily doses, 0.97 (95% CI 0.71-1.31); and for ≥2 defined daily doses, 0.94 (95% CI 0.72-1.23). The OR was similar for ACEIs and ARBs and in subgroups by age and sex. 29% of people with COVID-19 infection were hospitalized; the adjusted OR for hospitalization in relation to ACEI/ARB use was 0.92 (95% CI 0.54-1.57), and there was no association with dose. These findings support current recommendations that individuals on these medications continue their use.

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Figures

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; aOR, adjusted odds ratio; ARB, angiotensin receptor blocker; CCB, calcium channel blocker; CI, confidence interval; HTN, hypertension; 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; aOR, adjusted odds ratio; ARB, angiotensin receptor blocker; CCB, calcium channel blocker; CI, confidence interval; RAAS, renin-angiotensin-aldosterone system.
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