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

Abstract

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.

Keywords: COVID-19; angiotensin II receptor blocker; angiotensin-converting enzyme inhibitor; coronavirus; hypertension; inpatients.

Figure 1.

The flowchart showing the strategy of participant enrollment. ^a, 1128 participants with a history of hypertension enrolled in the hypertension cohort. ^b, 2302 participants without a history of hypertension enrolled in the nonhypertension cohort. ^c, 188 patients with hypertension who taking ACEI (angiotensin-converting enzyme inhibitor) or ARB (angiotensin II receptor blocker) during hospitalization were enrolled in the ACEI/ARB cohort. Patients discontinued treatment of hypertension due to inability to take medications or hypotension were not excluded from the cohort. ^d, 940 patients with hypertension who never taking ACEI and ARB during hospitalization were enrolled in the non-ACEI/ARB cohort. ^e, Propensity score-matched age, gender, cough, dyspnea, comorbidities (diabetes mellitus, coronary heart disease, and chronic renal disease), chest computerized tomography (CT)-diagnosed lung lesions, and incidence of increased CRP (C-reactive protein) and creatine. Hospital site as a random effect in the mixed-effect Cox model. ^f, 557 patients with antihypertension drug who never taking ACEI and ARB during hospitalization were enrolled in the secondary non-ACEI/ARB cohort. SARS-COV-2 indicates severe acute respiratory syndrome coronavirus 2.

Figure 2.

Kaplan-Meier curves for cumulative probability of Coronavirus disease 2019 (COVID-19) mortality during 28-day follow-up duration in ACEI (angiotensin-converting enzyme inhibitor)/ARB (angiotensin II receptor blocker) or non-ACEI/ARB cohort among 1128 patients with hypertension. The unmatched model and the median (interquartile range [IQR]) observation time was 28 (20–28) in ACEI/ARB cohort and 28 (19–28) in non-ACEI/ARB cohort (A). Propensity-score matched model and the median (IQR) observation time was 28 (20.5–28) in ACEI/ARB cohort and 28 (18–28) in non-ACEI/ARB cohort (B). The blips indicate censoring. HR indicates hazard ratio.