Angiotensin II receptor blocker or angiotensin-converting enzyme inhibitor use and COVID-19-related outcomes among US Veterans.

BACKGROUND: Angiotensin II receptor blockers (ARBs) and angiotensin-converting enzyme inhibitors (ACEIs) may positively or negatively impact outcomes in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We investigated the association of ARB or ACEI use with coronavirus disease 2019 (COVID-19)-related outcomes in US Veterans with treated hypertension using an active comparator design, appropriate covariate adjustment, and negative control analyses. METHODS AND FINDINGS: In this retrospective cohort study of Veterans with treated hypertension in the Veterans Health Administration (01/19/2020-08/28/2020), we compared users of (A) ARB/ACEI vs. non-ARB/ACEI (excluding Veterans with compelling indications to reduce confounding by indication) and (B) ARB vs. ACEI among (1) SARS-CoV-2+ outpatients and (2) COVID-19 hospitalized inpatients. The primary outcome was all-cause hospitalization or mortality (outpatients) and all-cause mortality (inpatients). We estimated hazard ratios (HR) using propensity score-weighted Cox regression. Baseline characteristics were well-balanced between exposure groups after weighting. Among outpatients, there were 5.0 and 6.0 primary outcomes per 100 person-months for ARB/ACEI (n = 2,482) vs. non-ARB/ACEI (n = 2,487) users (HR 0.85, 95% confidence interval [CI] 0.73-0.99, median follow-up 87 days). Among outpatients who were ARB (n = 4,877) vs. ACEI (n = 8,704) users, there were 13.2 and 14.8 primary outcomes per 100 person-months (HR 0.91, 95%CI 0.86-0.97, median follow-up 85 days). Among inpatients who were ARB/ACEI (n = 210) vs. non-ARB/ACEI (n = 275) users, there were 3.4 and 2.0 all-cause deaths per 100 person months (HR 1.25, 95%CI 0.30-5.13, median follow-up 30 days). Among inpatients, ARB (n = 1,164) and ACEI (n = 2,014) users had 21.0 vs. 17.7 all-cause deaths, per 100 person-months (HR 1.13, 95%CI 0.93-1.38, median follow-up 30 days). CONCLUSIONS: This observational analysis supports continued ARB or ACEI use for patients already using these medications before SARS-CoV-2 infection. The novel beneficial association observed among outpatients between users of ARBs vs. ACEIs on hospitalization or mortality should be confirmed with randomized trials.

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.

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.