Inpatient Omission of ACEi and ARBs Is Associated with Morbidity and Mortality in COVID-19: A Retrospective Cohort Study

Background: Due to the affinity of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) for the human angiotensin converting enzyme 2 (ACE2) receptor, use of angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) has been a major concern for clinicians during the 2020 pandemic. Meta-analyses have affirmed that these agents do not worsen clinical outcomes in SARS-CoV-2 infection. To date, only a limited number of studies have directly looked at the safety of inpatient prescription of ACEi/ARBs during acute COVID-19 illness. Methods: A retrospective cohort analysis was conducted to investigate the impact of inpatient provision of ACEi/ARBs on morbidity and mortality in patients admitted to hospital with COVID-19. Relationships were explored using linear and logistic regression. Findings: Six hundred and twelve adult patients met our inclusion criteria. The average age of our cohort was 69·6 ± 17·8 years, of which 354 (57·8%) were male. One hundred and fifty-one (24·7%) patients were established on ACEi/ARBs prior to admission. Despite correction for known confounders, discontinuation of ACEi/ARBs was highly predictive of worsened outcomes in COVID-19. The proportion of doses omitted in hospital was significantly associated with increased mortality (p<0·001, OR=9·59 [2·55-36·09]), maximum National Early Warning Score (NEWS-2; p<0·001, OR=1·66 [1·27-2·17]), maximum oxygen requirements (p<0·001, OR=3·00 [1·83-4·91]), and maximum C-Reactive Protein concentration (CRP; p=0·030, OR=1·83 [1·06-3·17]). Interpretation: While study interpretation needs to consider the impact of residual confounders, our data demonstrates a strong association between missed ACEi/ARB doses with increased morbidity and mortality. Given other studies support the safety of ACEi/ARB therapy in COVID-19 patients, our evidence supports continuation of current accepted practice surrounding ACEi/ARB therapy in acute illness – which is to limit drug omission to established acute contraindications, to actively monitor such decisions and to restart therapy as soon as it is safe to do so. Funding: None. Declaration of Interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf and declare: no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work. Ethics Approval Statement: The study received sponsorship from Epsom and St Helier University Hospitals NHS Trust. The requirement for ethical review was waived by The Office for Research Ethics Committees Northern Ireland (REC: 20/HRA/6061, IRAS: 283834).