ARB/ACEI use and severe COVID-19: a nationwide case-control study

BackgroundAngiotensin receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACEIs) have anti-inflammatory effects. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) uses the membrane protein angiotensin-converting enzyme 2 (ACE2), which is increased by ARB/ACEI treatment, as a cell entry receptor. Therefore, the use of ARBs/ACEIs for COVID-19 remains controversial. MethodsA retrospective case-control study was conducted using COVID-19 patients previously diagnosed with hypertension before COVID-19 onset. The primary outcome was severe infection or all-cause mortality. Cases included ARB/ACEI use for [≥]30 days during the 6 months before COVID-19 onset. Primary controls included antihypertensive use other than ARBs/ACEIs (narrow control); secondary controls included all other hypertension patients (broad control). We investigated ARB/ACEI association with outcomes in general and by subgroups (age, sex, and presence of diabetes) using logistic regression models with propensity score matching. FindingsOf 234427 suspected COVID-19 patients we screened, 1585 hypertension patients were analyzed. In the 892 cases, 428 narrow controls, and 693 broad controls, severe infection or death occurred in 8{middle dot}6%, 22{middle dot}2%, and 16{middle dot}7%, respectively. ARB/ACEI use was associated with a reduced risk of severe infection or death relative to the narrow control group (adjusted odds ratio [aOR] 0{middle dot}43, 95% confidence interval [CI] 0{middle dot}28 - 0{middle dot}65) and broad control group (aOR 0{middle dot}49, 95% CI 0{middle dot}33 - 0{middle dot}71). The association was smaller for newly diagnosed hypertension patients (aOR 0{middle dot}11, 95% CI 0{middle dot}03 - 0{middle dot}42 compared to narrow control group). ARB/ACEI protective effects against severe infection or death were significantly observed in male and diabetic patients. InterpretationARB/ACEI use was associated with a lower risk of severe infection or mortality compared to other antihypertensives or ARB/ACEI nonuse. FundingNone Research in contextO_ST_ABSEvidence before this studyC_ST_ABSAnimal studies reported that ACE2 attenuates lung injury and provides a protective effect against severe pneumonia. Additionally, retrospective studies found that ARBs/ACEIs may have beneficial effects on ARDS patient survival. Previous observational studies have reported no potential harmful association of either ARBs or ACEIs with COVID-19 outcomes. Added value of this studyBy analyzing nationwide claims data in South Korea, we found that previous use of ARB/ACEI was associated with improved outcomes in COVID-19 compared with either nonuse or use of a different class of antihypertensive drugs. The risk of severe infection or death was consistently about 55% lower in those treated with ARB/ACEIs than those who were not exposed to ARB/ACEIs. The protective effect of ARB/ACEI was remained significantly among the male subgroup and patients with diabetes. This association was also observed among COVID-19 patients with newly diagnosed hypertension. Implications of all the available evidenceThese results provide supporting evidence for the continued use of ARBs/ACEIs among patients with COVID-19. Moreover, for newly diagnosed hypertension patients, initiation of ARB/ACEI use may not adversely affect COVID-19 prognosis. Given the poor prognosis of COVID-19 patients with hypertension and lack of curable strategy, these findings may have considerable clinical implications in prevention of poor outcome in patients with hypertension.