Inpatient omission of ACEi and ARBs is associated with morbidity and mortality in COVID-19

Oddy, Christopher; Allignton, Jonathan; McCaul, James; Keeling, Polly; Senn, Dhanuja; Soni, Neesha; Morrison, Hannah; Mawella, Ruwani; Samuel, Thomas; Dixon, John

Purpose 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 of which 151 (24.7%) patients were established on ACEi/ARBs. 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]). Implications Our data demonstrates a strong association between missed ACEi/ARB doses with increased morbidity and mortality. The available 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.