Does taking an angiotensin inhibitor increase the risk for COVID-19? – a systematic review and meta-analysis

Abstract

Because SARS-COV2 entry into cells is dependent on angiotensin converting enzyme 2 (ACE2) and angiotensin converting enzyme inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) increase ACE2 activity, the safety of ACEI/ARB usage during the coronavirus disease 2019 (COVID-19) pandemic is a controversial topic. To address that issue, we performed a meta-analysis following The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Searches of the Embase, MEDLINE, PubMed, and Cochrane Library databases identified 16 case-control studies examining the effect of ACEI/ARB on the incidence of COVID-19 and its severity. ACEI/ARB usage was associated with an increased risk of COVID-19 morbidity (odds ratio (OR) 1.20, 95% confidence interval (CI) 1.07-1.33, P=0.001) among the general population but not in a hypertensive population (OR 1.05, 95% CI 0.90-1.21, P=0.553). ACEI/ARB usage was not associated with an increased risk of COVID-19 morbidity (coefficient 1.00, 95% CI 1.00-1.00, P=0.660) when we adjusted for hypertension in the general population. ACEI/ARB usage was also not associated with an increased risk of severe illness (OR 0.90, 95%CI 0.55-1.47, P=0.664) or mortality (OR 1.43, 95%CI 0.97-2.10, P=0.070) in COVID-19 patients. Our meta-analysis revealed that ACEI/ARB usage was not associated with either the increased risk of SARS-COV2 infection or the adverse outcomes in COVID-19 patients.

Association Between Baseline Use of Angiotensin‐Converting Enzyme Inhibitors and Angiotensin Receptor Blockers and Death Among Patients Tested for COVID‐19

“…Another study reported that ARBs were associated with reduced mortality in elderly patients with SARS‐CoV‐2 with type 2 diabetes mellitus, though curiously, this was not the case for ACEIs 15 . In contrast, some studies do not support an association between ACEIs/ARBs and negative outcomes 12,13,21–23 . Notably, a recent randomized, open‐label trial in which patients were randomly assigned to either continue or discontinue ACEI/ARB use did not support an association between stopping ACEIs/ARBs and negative outcomes 22 .…”

“…15 In contrast, some studies do not support an association between ACEIs/ARBs and negative outcomes. 12,13,[21][22][23] Notably, a recent randomized, open-label trial in which patients were randomly assigned to either continue or discontinue ACEI/ARB use did not support an association between stopping ACEIs/ARBs and negative outcomes. 22 However, this study was relatively small (n = 152) and ACEI/ARB use was changed only after infection.…”

Meta-analysis of the association between angiotensin pathway inhibitors and COVID-19 severity and mortality

“…These differences likely contributed to the conflicting findings between this and similar studies. Many analyses have found no significant difference in either COVID-19 severity or mortality related to ACEI/ARB prescription [ 55 , 56 , 58 , 61 ] whilst others have found significant reductions either for the whole population [ 54 , 57 , 62 ] or in sub-analyses, such as for patients with hypertension [ 59 , 60 ]. No studies have found an increased risk of severe disease or mortality from COVID-19 in relation to ACEI/ARB prescription.…”

“…No studies have found an increased risk of severe disease or mortality from COVID-19 in relation to ACEI/ARB prescription. Some analyses also examined the association between ACEI/ARB prescription and the risk of COVID-19 infection, which also varied depending on the class of agent (significant reduction with ACEI but not ARB) [ 57 ], and sub-analyses of the patient population (significant increase but not when adjusting for patients with hypertension) [ 58 ].…”

“…Additionally, given the retrospective design of most studies, selection bias remains an important problem [ 31 ]. Although not explored in the current meta-analysis, whether the prescription of ACEI/ARB has an association with the incidence of COVID-19 still remains unclear although a lack of such association has been reported [ 64 ], though others are conflicting [ 57 , 58 ].…”