Angiotensin Converting Enzyme Inhibitor and Angiotensin II Receptor Blocker Use Among Outpatients Diagnosed With COVID-19

Abstract

Coronavirus disease 2019 (COVID-19) is a viral pandemic precipitated by the severe acute respiratory syndrome coronavirus 2. Since previous reports suggested that viral entry into cells may involve angiotensin converting enzyme 2, there has been growing concern that angiotensin converting enzyme inhibitor (ACEI) and angiotensin II receptor blocker (ARB) use may exacerbate the disease severity. In this retrospective, single-center US study of adult patients diagnosed with COVID-19, we evaluated the association of ACEI/ARB use with hospital admission. Secondary outcomes included: ICU admission, mechanical ventilation, length of hospital stay, use of inotropes, and all-cause mortality. Propensity score matching was performed to account for potential confounders. Among 590 unmatched patients diagnosed with COVID-19, 78 patients were receiving ACEI/ARB (median age 63 years and 59.7% male) and 512 patients were non-users (median age 42 years and 47.1% male). In the propensity matched population, multivariate logistic regression analysis adjusting for age, gender and comorbidities demonstrated that ACEI/ARB use was not associated with hospital admission (OR 1.2, 95%CI 0.5 to 2.7, p = 0.652). CAD and CKD/end stage renal disease [ESRD] remained independently associated with admission to hospital. All-cause mortality, ICU stay, need for ventilation, and inotrope use was not significantly different between the 2 study groups. In conclusion, among patients who were diagnosed with COVID-19, ACEI/ ARB use was not associated with increased risk of hospital admission. Published by Elsevier Inc. (Am J Cardiol 2020;132:150−157) Coronavirus disease 2019 (COVID-19) is a viral pandemic precipitated by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerging in late December 2019 from Wuhan, Hubei Province, China. 1 Since then, the number of cases has exponentially increased around the globe, with over 9 million confirmed cases as of June 27, 2020. 2 Early in the pandemic, it was postulated that the use of renin-angiotensin-aldosterone-system (RAS) antagonists may independently affect health outcomes in patients with COVID-19. This hypothesis originates from the intricate interplay between the SARS-CoV-2 and RAS system; membrane bound angiotensin-converting enzyme 2 (ACE2) has been suggested to play an important role for SARS-CoV-2 entry into human cells. However, direct evidence for infection of cardiac tissue by SARS-CoV-2 and expression levels of ACE2 in different cardiac cell types remain unknown. Furthermore, patients with comorbidities including hypertension, diabetes mellitus, and chronic kidney disease (CKD) have higher circulating ACE2 expression, leading to a potentially additive effect with ACEI/ARB use. 3 Yet some experts contend that ACEIs/ARBs may be beneficial in these patients 4-the main substrate of ACE2 is angiotensin II, converting it to angiotensin 1-7 which causes vasodilation and hypotension. There remains a lack of clinical data regarding association of ACEI/ARB use and outcomes in humans infec...

The association of COVID-19 occurrence and severity with the use of angiotensin converting enzyme inhibitors or angiotensin-II receptor blockers in patients with hypertension

“…While this finding warrants further investigation, we do not believe it justifies a change in clinical practice. The lack of association between ACEI or ARB and COVID-19 severity both in our study and in earlier publications [ 23 , 26 – 28 ] further supports the notion that prescription of ACEI or ARB should not be discontinued in light of the rapidly changing pandemic.…”

“…We used a four-level COVID-19 severity measure and did not observe a consistent association between the use of either ACEI or ARB and disease severity. A previous study of 590 COVID-19 patients (78 ACEI/ARB users vs. 512 non-users) from a single center did not reveal any significant association between ACEI/ARB use and hospitalization, ICU admissions, mechanical ventilation, length of hospital stay, use of inotropes, or all-cause mortality [ 26 ]. A multi-center study of 338 patients yielded similar results: no significant associations between ACEI/ARB use and hospitalization, ICU admission, mechanical ventilation, or mortality.…”

“…Our study population consisted of 65.5% White,26.8% Black or African American, 0.8% Asian, 0.8% Native American or Alaska Native, 0.8% Native Hawaiian or other Pacific Islander, and 5.4% unreported race. Nearly 6.9% of the study population were Hispanic or Latino.…”

A comprehensive guide to the pharmacologic regulation of angiotensin converting enzyme 2 (ACE2), the SARS-CoV-2 entry receptor

“…In recent months, several clinical studies have reported that the use of ARBs and ACE-Inhs. does not affect disease progression and mortality rates in COVID-19 patients ( Anzola et al, 2020 ; Bae et al, 2020 ; Braude et al, 2020 ; Cordeanu et al, 2020 ; H. Cui et al, 2020 ; Di Castelnuovo et al, 2020 ; Gormez et al, 2020 ; Hippisley-Cox et al, 2020 ; Kalra et al, 2020 ; Khan et al, 2020 , Kim et al, 2020 ; Kocayigit et al, 2020 ; Lafaurie et al, 2020 ; J. Lee et al, 2020 ; Sardu et al, 2020 ; Soleimani et al, 2020 , Taher et al, 2020 ; Trifirò et al, 2020 , Wang et al, 2020 ). Altogether, these results indicate that the use of ACE-Inhs.…”

Medical management of COVID-19 clinic

“…Unfortunately, in latest guidelines by both the WHO and National Institutes of Health (NIH), the above discussed agents are all recommended not to be administered outside of the context of clinical trials [ 41 - 42 ] . Other agents targeting angiotensin-converting enzyme 2 (ACE2) receptor system [ 43 ] or lipid metabolism [ 44 ] are in even more preliminary exploration stage. We are likely still only in the beginning of our battle with SARS-CoV-2.…”