Abstract
Objectives: SARS-CoV-2 enters cells using the ACE2 receptor. Medications that affect ACE2 expression or function such as angiotensin receptor blockers (ARBs) and ACE inhibitors (ACE-I) and metformin have the potential to counter the dysregulation of ACE2 by the virus and protect against viral injury. Here, we describe COVID-19 survival associated with ACE-I, ARB and metformin use.
Design: This is a hospital-based observational study of patients with COVID-19 infection using logistic regression with correction for pre-existing conditions and propensity score weighted Cox proportional hazards models to estimate associations between medication use and mortality.
Setting: Medical record data from the US Veterans Affairs (VA) were used to identify patients with a reverse transcription PCR diagnosis of COVID-19 infection, to classify patterns of ACE inhibitors (ACE-I), ARB, beta blockers, metformin, famotidine and remdesivir use, and, to capture mortality.
Participants: 9532 hospitalised patients with COVID-19 infection followed for 60 days were analysed.
Outcome measure: Death from any cause within 60 days of COVID-19 diagnosis was examined.
Results: Discontinuation of ACE-I was associated with increased risk of death (OR: 1.4; 95% CI 1.2-1.7). Initiating (OR: 0.3; 95% CI 0.2-0.5) or continuous (OR: 0.6; 95% CI 0.5-0.7) ACE-I was associated with reduced risk of death. ARB and metformin associations were similar in direction and magnitude and also statistically significant. Results were unchanged when accounting for pre-existing morbidity and propensity score adjustment.
Conclusions: Recent randomised clinical trials support the safety of continuing ACE-I and ARB treatment in patients with COVID-19 where indicated. Our study extends these findings to suggest a possible COVID-19 survival benefit for continuing or initiating ACE-I, ARB and metformin medications. Randomised trials are appropriate to confirm or refute the therapeutic potential for ACE-I, ARBs and metformin.
Keywords: COVID-19; epidemiology; public health.
【저자키워드】 COVID-19, public health, Epidemiology, 【초록키워드】 Treatment, public health, SARS-CoV-2, ACE2, Mortality, Infection, Remdesivir, ACE2 receptor, medications, virus, ARB, survival, morbidity, Patient, COVID-19 diagnosis, death, Logistic regression, ACE inhibitor, medication, reverse transcription PCR, ACE2 expression, randomised clinical trial, association, angiotensin receptor blocker, Injury, ARBs, dysregulation, medical record, Support, Randomised trial, Beta blockers, 95% CI, increased risk, reduced risk, therapeutic potential, veteran, Affect, recent, benefit, Cell, PROTECT, Result, identify, examined, indicated, analysed, condition, were used, magnitude, hospitalised patient, statistically significant, Affair, Cox proportional hazard, diagnosis of COVID-19, Initiating, patients with COVID-19, with COVID-19, 【제목키워드】 Mortality, medication,