No association between use of angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers prior to hospital admission and clinical course of COVID-19 in the COvid MEdicaTion (COMET) study

Abstract

Since the outbreak of SARS-CoV-2, also known as COVID-19, conflicting theories have circulated on the influence of angiotensin-converting enzyme inhibitors (ACEi) and angiotensin II receptor blockers (ARB) on incidence and clinical course of COVID-19, but data are scarce. The COvid MEdicaTion (COMET) study is an observational, multinational study that focused on the clinical course of COVID-19 (i.e. hospital mortality and intensive care unit [ICU] admission), and included COVID-19 patients who were registered at the emergency department or admitted to clinical wards of 63 participating hospitals. Pharmacists, clinical pharmacologists or treating physicians collected data on medication prescribed prior to admission. The association between the medication and composite clinical endpoint, including mortality and ICU admission, was analysed by multivariable logistic regression models to adjust for potential confounders. A total of 4870 patients were enrolled. ACEi were used by 847 (17.4%) patients and ARB by 761 (15.6%) patients. No significant association was seen with ACEi and the composite endpoint (adjusted odds ratio [OR] 0.94; 95% confidence interval [CI] 0.79 to 1.12), mortality (OR 1.03; 95%CI 0.84 to 1.27) or ICU admission (OR 0.96; 95%CI 0.78 to 1.19) after adjustment for covariates. Similarly, no association was observed between ARB and the composite endpoint (OR 1.09; 95%CI 0.90 to 1.30), mortality (OR 1.12; OR 0.90 to 1.39) or ICU admission (OR 1.21; 95%CI 0.98 to 1.49). In conclusion, we found no evidence of a harmful or beneficial effect of ACEi or ARB use prior to hospital admission on ICU admission or hospital mortality.

Keywords: COVID-19; SARS-CoV-2; angiotensin II receptor blocker; angiotensin-converting enzyme inhibitor; mortality.

FIGURE 1

Schematic illustration of the renin–angiotensin–aldosterone system including the role of ACE2 and link with SARS‐CoV‐2 infection. (A) ACE2 converts angiotensin II to Ang (1–7) and angiotensin I to Ang (1–9). Ang (1–7) and Ang (1–9) have an organic‐protective effect and counterbalance the negative effects of binding AT₁R by angiotensin II. (B) Binding of SARS‐CoV‐2 on ACE2 internalize the virus into the cell. ACE2 may be upregulated by renin–angiotensin–aldosterone system inhibitor, leading to the hypothesis that the infectivity of SARS‐CoV‐2 increases. However, due to the beneficial effects shown in (A), this increase in ACE2 might also be beneficial due to protection against inflammation and lung injury in conditions known for low ACE2 expression, such as diabetes and hypertension. Abbreviations: ACE, angiotensin converting enzyme; ACEi, ACE inhibitor; Ang, angiotensin; ARB, angiotensin receptor blocker; AT₁R, type 1 angiotensin II receptor, AT₂R; type 2 angiotensin II receptor; MasR, Mas receptor