Association of Inpatient Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Mortality Among Patients With Hypertension Hospitalized With COVID-19

Zhang, Peng; Zhu, Lihua; Cai, Jingjing; Lei, Fang; Qin, Juan-Juan; Xie, Jing; Liu, Ye-Mao; Zhao, Yan-Ci; Huang, Xuewei; Lin, Lijin; Xia, Meng; Chen, Ming-Ming; Cheng, Xu; Zhang, Xiao; Guo, Deliang; Peng, Yuanyuan; Ji, Yan-Xiao; Chen, Jing; She, Zhi-Gang; Wang, Yibin; Xu, Qingbo; Tan, Renfu; Wang, Haitao; Lin, Jun; Luo, Pengcheng; Fu, Shouzhi; Cai, Hongbin; Ye, Ping; Xiao, Bing; Mao, Weiming; Liu, Liming; Yan, Youqin; Liu, Mingyu; Chen, Manhua; Zhang, Xiao-Jing; Wang, Xinghuan; Touyz, Rhian M.; Xia, Jiahong; Zhang, Bing-Hong; Huang, Xiaodong; Yuan, Yufeng; Rohit, Loomba; Liu, Peter P.; Li, Hongliang

RATIONALE: Use of ACEIs (angiotensin-converting enzyme inhibitors) and ARBs (angiotensin II receptor blockers) is a major concern for clinicians treating coronavirus disease 2019 (COVID-19) in patients with hypertension. OBJECTIVE: To determine the association between in-hospital use of ACEI/ARB and all-cause mortality in patients with hypertension and hospitalized due to COVID-19. METHODS AND RESULTS: This retrospective, multi-center study included 1128 adult patients with hypertension diagnosed with COVID-19, including 188 taking ACEI/ARB (ACEI/ARB group; median age 64 [interquartile range, 55–68] years; 53.2% men) and 940 without using ACEI/ARB (non-ACEI/ARB group; median age 64 [interquartile range 57–69]; 53.5% men), who were admitted to 9 hospitals in Hubei Province, China from December 31, 2019 to February 20, 2020. In mixed-effect Cox model treating site as a random effect, after adjusting for age, gender, comorbidities, and in-hospital medications, the detected risk for all-cause mortality was lower in the ACEI/ARB group versus the non-ACEI/ARB group (adjusted hazard ratio, 0.42 [95% CI, 0.19–0.92]; P=0.03). In a propensity score-matched analysis followed by adjusting imbalanced variables in mixed-effect Cox model, the results consistently demonstrated lower risk of COVID-19 mortality in patients who received ACEI/ARB versus those who did not receive ACEI/ARB (adjusted hazard ratio, 0.37 [95% CI, 0.15–0.89]; P=0.03). Further subgroup propensity score-matched analysis indicated that, compared with use of other antihypertensive drugs, ACEI/ARB was also associated with decreased mortality (adjusted hazard ratio, 0.30 [95% CI, 0.12–0.70]; P=0.01) in patients with COVID-19 and coexisting hypertension. CONCLUSIONS: Among hospitalized patients with COVID-19 and coexisting hypertension, inpatient use of ACEI/ARB was associated with lower risk of all-cause mortality compared with ACEI/ARB nonusers. While study interpretation needs to consider the potential for residual confounders, it is unlikely that in-hospital use of ACEI/ARB was associated with an increased mortality risk.