Association of Renin-angiotensin-aldosterone System Inhibitors With Coronavirus Disease 2019 (COVID-19)- Related Outcomes in Korea: A Nationwide Population-based Cohort Study

Abstract

Background Renin-angiotensin-aldosterone system (RAAS) inhibitors may facilitate host cell entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) or attenuate organ injury via RAAS blockade. We aimed to assess the associations between prior use of RAAS inhibitors and clinical outcomes among Korean patients with coronavirus 2019 (COVID-19). Methods We performed a nationwide population-based cohort study using the Korean Health Insurance Review and Assessment database. Claim records were screened for 66793 individuals who were tested for COVID-19 until April 8, 2020. Adjusted odds ratios (ORs) were used to compare the clinical outcomes between RAAS inhibitor users and nonusers. Results Among 5179 confirmed COVID-19 cases, 762 patients were RAAS inhibitor users and 4417 patients were nonusers. Relative to nonusers, RAAS inhibitor users were more likely to be older, male, and have comorbidities. Among 1954 hospitalized patients with COVID-19, 377 patients were RAAS inhibitor users and 1577 patients were nonusers. In-hospital mortality was observed for 33 RAAS inhibitor users (9%) and 51 nonusers (3%) (p<0.001). However, after adjustment for age, sex, Charlson Comorbidity Index, immunosuppression, and hospital type, the use of RAAS inhibitors was not associated with a higher risk of mortality (adjusted OR, 0.88; 95% confidence interval, 0.53–1.44; p=0.60). No significant differences were observed between RAAS inhibitor users and nonusers in terms of vasopressor use, modes of ventilation, extracorporeal membrane oxygenation, renal replacement therapy, and acute cardiac events. Conclusions Our findings suggest that prior use of RAAS inhibitors was not independently associated with mortality among COVID-19 patients in Korea.

Angiotensin converting enzyme inhibitors and angiotensin II receptor blockers and outcomes in patients with COVID-19: a systematic review and meta-analysis

“…This indicates that there at least does not seem to be evidence of harm in ACEI/ARB usage among COVID-19 patients. In the 4 studies [26,27,33,34,37] where the unadjusted data showed a higher rate of mortality or severe disease, only the study by Selcuk et al, showed potential harm after adjustment for potential confounders [26]. However, it should be noted that this study had a small sample size of 113 patients hence, only a limited number of variables could be included in the regression model (not even gender and race were included) and other potential unknown confounders cannot be accounted for.…”

“…A total of 21 studies were included in the final meta-analysis [2,7,[19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36][37]. Majority of the studies included had low to serious risk of bias in relation to the specific focus which was ACEI/ARB use and clinical outcomes, but no studies included had critical risk of bias.…”

Mortality and Disease Severity Among COVID-19 Patients Receiving Renin-Angiotensin System Inhibitors: A Systematic Review and Meta-analysis

“…The characteristics of the shortlisted studies are summarized in Table 1. Among shortlisted studies, 23 studies were from China , nine studies were from Italy [64][65][66][67][68][69][70][71][72], ten studies were from the United States [83][84][85][86][87][88][89][90][91][92], four studies were from South Korea [75][76][77][78], three studies were from France [60][61][62], two studies were from Spain [79,80], one study each was from Belgium [35], Denmark [59], Hong Kong [63], Kuwait [73], Singapore [74], Turkey [81], and the United Kingdom [82]; and one study included data from 38 countries [93]. There were 24 studies that included hypertensive patients exclusively (100%) [36, 38, 39, 43-45, 47, 48, 50-52, 54, 56, 58, 66, 71, 72, 75, 78, 81, 87-89, 91].…”

“…Since Selçuk et al [81] provided mortality estimates with a very wide CI (OR = 3.66; 95% CI 1.11-18.18), we excluded this study from our meta-analysis. In a pooled analysis of the 12 remaining original studies that provided adjusted ORs, with 18,749 COVID-19 patients being analyzed [35,64,66,75,76,78,80,86,88,89,92,93], the use of an ACEI/ARB was significantly associated with lower odds of mortality compared to non-use of an ACEI/ARB ( Fig. 2; pooled OR = 0.73, 95% CI 0.56-0.95).…”

“…Subgroup analysis based on the region where the studies were performed demonstrated a non-significant association with lower odds of mortality in studies originated from East Asia (Supplementary Table S2; pooled OR = 0.76, 95% CI 0.44-1.31)[75,76,78], Europe (Supplementary Table S2; pooled OR = 0.51, 95% CI 0.21-1.25)[35,64,66,80], and the United States (Supplementary…”