ABSTRACT
Importance The ACE D allele is more prevalent among African Americans (AA) compared to other races/ethnicities and has previously been associated with severe COVID-19 pathogenesis through excessive ACE1 activity. ACE-I/ARBs may counteract this mechanism, but their association with COVID-19 outcomes has not been specifically tested in the AA population. Objectives To determine whether the use of ACE-I/ARBs is associated with COVID-19 in-hospital mortality in AA compared with non-AA population. Design, Setting, and Participants In this observational, retrospective study, patient-level data were extracted from the Mount Sinai Health System’s (MSHS) electronic medical record (EMR) database, and 6,218 patients with a laboratory-confirmed COVID-19 diagnosis from February 24 to May 31, 2020 were identified as ACE-I/ARB users. Exposures Patients with an active prescription from January 1, 2019 up to the date of admission for ACE-I/ARB (outpatient use) and patients administered ACE-I/ARB during hospitalization (in-hospital use) were identified. Main Outcomes and Measures The primary outcome was in-hospital mortality, assessed in the entire, AA, and non-AA population. Results Of the 6,218 COVID-19 patients, 1,138 (18.3%) were ACE-I/ARB users. In a multivariate logistic regression model, ACE-I/ARB use was independently associated with reduced risk of in-hospital mortality in the entire population (OR, 0.655; 95% CI, 0.505-0.850; P=0.001), AA population (OR, 0.44; 95% CI, 0.249-0.779; P=0.005), and non-AA population (OR, 0.748, 95% CI, 0.553-1.012, P=0.06). In the AA population, in-hospital use of ACE-I/ARBs was associated with improved mortality (OR, 0.378; 95% CI, 0.188-0.766; P=0.006) while outpatient use was not (OR, 0.889; 95% CI, 0.375-2.158; P=0.812). When analyzing each medication class separately, ARB in-hospital use was significantly associated with reduced in-hospital mortality in the AA population (OR, 0.196; 95% CI, 0.074-0.516; P=0.001), while ACE-I use was not associated with impact on mortality in any population. Conclusion and Relevance In-hospital use of ARBs was associated with a significant reduction in in-hospital mortality among COVID-19-positive AA patients. These results support further investigation of ARBs to improve outcomes in AA patients at high risk for COVID-19-related mortality.
Subject(s)
COVID-19ABSTRACT
Importance: Alpha-1-adrenergic receptor antagonists (1-blockers) can abrogate pro-inflammatory cytokines and may improve outcomes among patients with respiratory infections. Repurposing readily available drugs such as 1-blockers could augment the medical response to the COVID-19 pandemic. Objective: To evaluate the association between 1-blocker exposure and COVID-19 mortality Design: Real-world evidence study Setting: Patient level data with 32,355 records tested for SARS-CoV-2 at the Mount Sinai Health System including 8,442 laboratory-confirmed cases extracted from five member hospitals in the New York City metropolitan area. Participants: 2,627 men aged 45 or older admitted with COVID-19 between February 24 and May 31, 2020 Exposures: 1-blocker use as an outpatient or while admitted for COVID-19 Main Outcomes and Measures: In-hospital mortality Results: Men exposed to 1-blockers (N=436) were older (median age 73 vs. 64 years, P<0.001) and more likely to have comorbidities than unexposed men (N=2,191). Overall, 758 (28.9%) patients died in hospital, 1,589 (60.5%) were discharged, and 280 (10.7%) were still hospitalized as of May 31, 2020. Outpatient exposure to 1-blockers was not associated with COVID-19 hospital outcomes, though there was a trend towards significance (OR 0.749, 95% CI 0.527-1.064; P=0.106). Conversely, inpatient use of 1-blockers was independently associated with improved in-hospital mortality in both multivariable logistic (OR 0.633, 95% CI 0.434-0.921; P=0.017) and Cox regression analyses (HR 0.721, 95% CI 0.572-0.908; P=0.006) adjusting for patient demographics, comorbidities, and baseline vitals and labs. Age-stratified analyses suggested greater benefit from inpatient 1-blocker use among younger age groups: Age 45-65 OR 0.384, 95% CI 0.164-0.896 (P=0.027); Age 55-75 OR 0.511, 95% CI 0.297-0.880 (P=0.015); Age 65-89 OR 0.810, 95% CI 0.509-1.289 (P=0.374). Conclusions and Relevance: Inpatient 1-blocker use was independently associated with improved COVID-19 mortality among hospitalized men. Clinical trials to assess the therapeutic value of 1-blockers in COVID-19 are warranted.