Association of the patterns of use of medications with mortality of COVID-19 infection: a hospital-based observational study

Abstract

ObjectivesSARS-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.DesignThis 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.SettingMedical 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.Participants9532 hospitalised patients with COVID-19 infection followed for 60 days were analysed.Outcome measureDeath from any cause within 60 days of COVID-19 diagnosis was examined.ResultsDiscontinuation 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.ConclusionsRecent 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.

Kidney replacement therapy patients with COVID-19 in the vaccine era: what do we need to know?

“…The main mechanism was suggested to be the blocking of the active role of angiotensin receptor-1 on SARS-CoV-2 entry into cells by soluble angiotensin-converting enzyme 2 [ 19 ]. Supporting the results, initiation or continuation of RAS blocker reduced the death risk, whereas discontinuation increased the risk [ 20 ]. A recent meta-analysis indicated no significant benefit or harm from RAS blocker use for either susceptibility, illness severity or mortality of COVID-19 infection [ 21 ].…”

Metformin in SARS-CoV-2 infection: A hidden path – from altered inflammation to reduced mortality. A review from the literature

“…Wang et al 44 analyzed 39,829 T2D patients treated with metformin or another glucose lowering drug and verified that the prescription of metformin in primary care does not influence susceptibility to COVID-19, neither COVID-19 related mortality (HR 0.89; 95 % CI 0.74–1.07). On the analysis of 9532 United States (US) Veterans with COVID-19, Wallace et al 45 found a reduced risk of mortality with the maintenance of metformin during hospitalization (OR 0.35; 95 % CI 0.28–0.45) and with its initiation at admission (OR 0.19; 95 % CI 0.07–0.47) and an increased risk of mortality with its withdrawal (OR 1.54; 95 % CI 1.30–1.82). Orioli et al 46 analyzed diabetic patients with confirmed COVID-19 and compared survivors to non-survivors, and confirmed that the latter were less often treated with metformin ( p = 0.036).…”

SARS-CoV-2 and the Angiotensin-Converting Enzyme 2 Receptor: Angiotensin-Converting Enzyme Inhibitor/Angiotensin 2 Receptor Blocker Utilization and a Shift Towards the Renin-Angiotensin-Aldosterone System Classical Pathway

“…The safety of continued ACEi and ARB medication in patients with COVID-19, where needed, is supported by recent randomized clinical trials. This study expands on these conclusions by suggesting that metformin, ACEi, and ARB therapy may be continued or started to improve COVID-19 survival [ 11 ].…”