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

Abstract

Background A number of studies have reported the association between the use of angiotensin-converting enzyme inhibitor (ACEI) and angiotensin-II receptor blocker (ARB) medications and the occurrence or severity of coronavirus disease 2019 (COVID-19). Published results are inconclusive, possibly due to differences in participant comorbidities and sociodemographic backgrounds. Since ACEI and ARB are frequently used anti-hypertension medications, we aim to determine whether the use of ACEI and ARB is associated with the occurrence and severity of COVID-19 in a large study of US Veterans with hypertension. Methods Data were collected from the Department of Veterans Affairs (VA) National Corporate Data Warehouse (VA-COVID-19 Shared Data Resource) between February 28, 2020 and August 18, 2020. Using data from 228,722 Veterans with a history of hypertension who received COVID-19 testing at the VA, we investigated whether the use of ACEI or ARB over the two years prior to the index date was associated with increased odds of (1) a positive COVID-19 test, and (2) a severe outcome (hospitalization, mortality, and use of intensive care unit (ICU) and/or mechanical ventilation) among COVID-19-positive patients. We used logistic regression with and without propensity score weighting (PSW) to estimate the odds ratio (OR) and 95% confidence interval (95% CI) for the association between ACEI/ARB use and a positive COVID-19 test result. The association between medication use and COVID-19 outcome severity was examined using multinomial logistic regression comparing participants who were not hospitalized to participants who were hospitalized, were admitted to the ICU, used a mechanical ventilator, or died. All models were adjusted for relevant covariates, including demographics (age, sex, race, ethnicity), selected comorbidities, and the Charlson Comorbidity Index (CCI). Results The use of ACEI significantly decreased the odds of a positive COVID-19 test among Veterans with hypertension (OR = 0.917, (0.887, 0.948) and OR = 0.926, (0.894, 0.958) with PSW). The use of ACEI, but not of ARB, was also associated with significantly increased odds of using mechanical ventilators (OR = 1.265, (1.010, 1.584) and OR = 1.210, (1.053, 1.39) with PSW) among all COVID-19 inpatients compared to outpatients. Conclusions In this study of Veterans with hypertension, ACEI was significantly associated with decreased odds of testing positive for COVID-19. With the exception of the association of ACEI with a small non-clinically-important increase in the odds of using mechanical ventilators, neither ACEI nor ARB was found to be associated with clinical severity or mortality among COVID-19-positive Veterans. The results of this study need further corroboration and validation in other cohort samples outside the VA.

Neutralizing antibody responses over time in demographically and clinically diverse individuals recovered from SARS-CoV-2 infection in the United States and Peru: A cohort study

“…One hypothesis postulates that ACE inhibitors and/or ARBs, taken by approximately 65% of our participants with hypertension, may mediate changes in baseline inflammation or in ACE2 receptor expression or affinity through the renin-angiotensin-aldosterone system [ 70 ]. Large meta-analyses and observational studies have not confirmed this hypothesis [ 70 – 72 ], but if ACE2 or related receptors are down-regulated and viral replication is thus initially limited, lower nAb responses may reflect less early antigen stimulation. We saw no statistically significant difference in nAb responses between hypertensive individuals who did or did not report ARB or ACE inhibitor use, but few participants were not on these medications and the directionality of the nonsignificant differences we observed—lower odds of a nAb response and lower titers among those on ARBs or ACE inhibitors—are consistent with this hypothesis.…”

Renin-angiotensin-aldosterone system inhibitors – a realm of confusion in COVID-19

“…Interestingly, the use of ACEI was significantly associated with a higher risk of hospitalization and mechanical ventilation compared to non-users or ARB users. The study of Li et al [23] showed that neither ACEI nor ARB use was associated with increased mortality or other adverse events for the COVIDtreated patients than ACEI/ARB-non-users [23]. However, such an extensive study has some limitations: the majority of the patients (around 93%) were male; the study did not consider the use of diuretics in the previous treatment of the patients and other sources of bias/confounder factors.…”

“…Such categories are older, hypertensive, male patients, diabetes, chronic kidney, and cardiovascular disease. The same categories of patients are also known to receive more frequent medication, including ACEI/ARBs [18,19,22,23]. Therefore, understanding the exact effects and mechanism of action of RAAS inhibitors becomes a matter of particular importance.…”

“…Therefore, most of these studies' results are contrary to what was previously suspected, and the real mechanism by which these medications intervene in SARS-CoV-2 infection is only partially understood. There are still reports that remain inconclusive [23], and even the up-regulation of the ACE2 receptors in RAAS users is now questioned. In this regard, some studies have even started to question the frequency of the ACE2 overexpression after RAAS-inhibitors treatment or require additional evidence [18,39].…”

Skrining Faktor Komorbid Hipertensi pada Sasaran Lansia Vaksinasi Covid-19

“…Hampir dua pertiga orang di atas 60 tahun memiliki tekanan darah tinggi (WebMD, 2021). Kemungkinan penyebab lainnya ialah akibat penggunaan obat antihipertensi golongan ACE inhibitor dan angiotensin receptor blocker (ARB), yang dapat meningkatkan kadar Shirly Gunawan, enzim yang disebut angiotensin converting enzyme 2 (ACE2) di dalam tubuh (Li et al, 2021)…”