key: cord-0946866-x019odsd
authors: Bae, Seongman; Kim, Ju Hyeon; Kim, Ye-Jee; Lim, Joon Seo; Yun, Sung-Cheol; Kim, Young-Hak; Lee, Sang-Oh; Kim, Sung-Han
title: Effects of Recent Use of Renin-Angiotensin System Inhibitors on Mortality of Patients with Coronavirus Disease 2019
date: 2020-10-27
journal: Open Forum Infect Dis
DOI: 10.1093/ofid/ofaa519
sha: 061d7cd5c712acb908b430b96ea64fcda4e7861a
doc_id: 946866
cord_uid: x019odsd

BACKGROUND: There is a growing concern about the potential harmful effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) in patients with COVID-19 and cardiovascular diseases (CVDs). The aim of this study was to evaluate the association between recent exposure to ACEIs/ARBs and in-hospital mortality in patients with COVID-19. METHODS: We used the data from a nationwide cohort of patients with COVID-19 from the health insurance claims data of South Korea, which were released for research purposes for public health by the Ministry of Health and Welfare of South Korea. Patients with COVID-19 were identified using the relevant diagnostic code. Propensity score-matching (1:1) was carried out among patients with CVD according to the type of medication (ACEIs/ARBs vs. other), and the risk of death was assessed. RESULTS: A total of 4936 patients with COVID-19 were analyzed, of whom 1048 (21.2%) had CVD. Of the 1048 patients with CVD, 864 (82.4%) received at least one anti-hypertensive medication prior to the diagnosis of COVID-19, including 359 (41.6%) who received ACEIs/ARBs and 505 (58.4%) who received drugs other than ACEIs/ARBs. Using the propensity scores for ACEIs/ARBs use, we matched 305 pairs of patients receiving ACEIs/ARBs and patients receiving other drugs. The recent use of ACEIs/ARBs was not significantly associated with in-hospital mortality in unadjusted analysis (odds ratio [OR], 0.62; 95% CI, 0.33 to 1.14) and propensity score-matching analysis (OR, 1.00; 95% CI, 0.46 to 2.16). CONCLUSION: In patients with COVID-19 and underlying CVDs, the recent use of ACEIs/ARBs was not significantly associated with in-hospital mortality. These findings do not support stopping or modifying ACEIs/ARBs in patients amidst the current COVID-19 pandemic.

The morbidity and mortality associated with the ongoing coronavirus disease 2019 27 pandemic are particularly severe in older adults with underlying cardiovascular 28 diseases (CVDs), who are commonly treated with renin-angiotensin system (RAS) inhibitors 29 such as angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor 30 blockers (ARBs). 1,2 Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) enters 31 host cells by interacting with angiotensin-converting enzyme 2 (ACE2) as the receptor. 3

Notably, increased ACE2 expression has been shown to be associated with RAS inhibitors in 33 animal model, 4 there is a growing concern that continuing RAS inhibitor treatment in patients 34 with COVID-19 may negatively affect the clinical outcomes. On the other hand, ACE2 has 35 been shown to have a significant protective role in severe acute lung injuries, 5,6 suggesting 36 that RAS inhibitors may confer clinical benefits rather than harm in COVID-19 by 37 upregulating the expression of ACE2. We thus evaluated the effects of recent exposure to 38 ACEIs/ARBs on the in-hospital mortality of patients with COVID-19 and underlying CVDs. M a n u s c r i p t 6 Methods 40 Study design and database 41 This study was conducted using the National Health Insurance (NHI) Medical Center (S2020-0489), which waived the requirement for written or verbal consent 57 from the patients based on the observational nature of the study and the fact that the patient 58 identifiers were fully encrypted prior to analysis. Underlying comorbidities were identified using the ICD-10 codes when two or more hospital 70 visits with the relevant diagnostic codes within a year prior to the index date were recorded.

Patients with CVDs included those with hypertension, ischemic heart disease, or heart failure 72 as described elsewhere. 9 Prescription history was determined when records of Table 1 ).

Each individual in the ACEIs/ARBs group was matched with those in the active 90 comparator group at a 1:1 ratio using propensity scores. The propensity score-matched pairs In addition, several sensitivity analyses were performed to test the robustness of our findings.

These analyses included subjects excluding patients with heart failure, and subjects excluding 101 those with heart failure or ischemic heart disease.

All reported P values are two-sided, and those <.05 were considered statistically 103 significant. Data manipulation and statistical analyses were conducted using SAS ® version 104 9.2 (SAS Institute Inc., Cary, NC, USA).

of ACEIs/ARBs was not significantly associated with mortality (odds ratio [OR], 0.62; 95% 126 CI, 0.33 to 1.14; Table 2 ). After propensity score matching, all variables were adjusted and 127 the SDM for each variable was less than 10% (Table 1 ). In the matched cohort, both groups 128 consisted of 305 patients. Propensity score-matching analysis also revealed that the recent use M a n u s c r i p t 10 of ACEIs/ARBs was not significantly associated with mortality (4.6% [14/305] Abbreviation: PS, propensity score; OR, odds ratio; CI, confidence interval.

Clinical Characteristics of Coronavirus Disease

Characteristics of and Important Lessons From the 204

COVID-19) Outbreak in China: Summary of a

Cases From the Chinese Center for Disease Control and Prevention

SARS-CoV-2 Cell Entry Depends

A c c e p t e d M a n u s c r i p t