Angiotensin-Converting Enzyme Inhibitors Versus Angiotensin II Receptor Blockers

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) utilizes membrane-bound ACE2 (angiotensin-converting enzyme 2) as a functional receptor to gain entry into host cells. An early finding of the coronavirus disease 2019 (COVID-19) pandemic was the high mortality observed in patients with hypertension, diabetes mellitus, and coronary heart disease,¹ raising concerns with regard to the potential for increased risk of SARS-CoV-2 infection and adverse outcomes in patients taking either ACE inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs). These concerns largely stemmed from the possible upregulation of ACE2 expression by these medications, although literature exists to both support and refute this notion.^2,3 Observational studies in patients with COVID-19 have since shown no association between the use of either ACEIs or ARBs and testing positive for SARS-CoV-2.^4,5 Whether a differential impact of ACEIs compared with ARBs on outcomes in COVID-19 exists remains uncertain. We sought to report on the association of ACEIs compared with ARBs on the risk of hospital admission, intensive care unit (ICU) admission, and need for mechanical ventilation in patients diagnosed with COVID-19.

The data that support the findings of this study are available from the corresponding author upon request. A retrospective cohort analysis of an observational, institutional review board-approved registry of all patients who were tested for COVID-19 in the Cleveland Clinic Health System between March 8, 2020 and May 8, 2020 was conducted. Data regarding baseline characteristics, medications, test results, use of ACEI or ARB, and outcomes were extracted from EPIC electronic medical record system. Subjects recorded as being on both an ACEI and an ARB were excluded from the analysis. To account for the heterogeneity in the medical comorbidities among patients taking ACEI and ARB, an overlap propensity-score weighting was performed, as previously published.⁴ The primary outcome of interest was a head-to-head comparison of incidence of a severe disease process as assessed by hospital admission, ICU admission, and requirement for mechanical ventilation in patients with COVID-19 who were on ACEI versus ARB. All statistical analyses were performed using SAS version 9.4 (SAS Institute). P values were 2-sided, with a significance threshold of 0.05.

The data set consisted of 39 042 patients tested for SARS-CoV-2. A total of 117 patients were tested multiple times for COVID-19. Data regarding only the index test was used for analysis in such cases to avoid duplication. The mean (SD) age was 65 (14) years, 2758 (51%) were male, and 3867 (72%) were White. Among all tested patients, 3094 (58%) were taking ACEIs and 2277 (42%) were taking ARBs. Among these 5371 tested patients, 381 (7.1%) tested positive (219 on ACEIs and 162 on ARBs). After overlap propensity-score weighting, the test positivity rate was 7.0% in ACEIs compared with 7.4% in ARBs group (overlap propensity score–weighted odds ratio, 0.95 [95% CI, 0.77–1.17]; Figure). Among patients with positive test results, overlap propensity-score weighting demonstrated the following: 58% taking ACEIs (versus 59% taking ARBs) were admitted to the hospital (odds ratio, 0.95 [95% CI, 0.62–1.45]); 22% taking ACEIs (versus 19% taking ARBs) were admitted to an ICU (odds ratio, 1.15 [95% CI, 0.69–1.92]); and 12% taking ACEIs (versus 11% taking ARBs) required mechanical ventilation (odds ratio, 1.12 [95% CI, 0.59–2.15]; Figure). A total of 21 deaths (5.6%) occurred. Fifteen of the 219 patients (6.9%) were taking an ACEI and 6 of 162 (3.7%) were taking an ARB.