Angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers and the risk of COVID-19 infection or severe disease: Systematic review and meta-analysis

Abstract

Objective Animal studies suggested that angiotensin-converting enzyme inhibitors (ACEi) and angiotensin-receptor blockers (ARB) facilitate the inoculation of potentially leading to a higher risk of infection and/or disease severity. We aimed to systematically evaluate the risk of COVID-19 infection and the risk of severe COVID-19 disease associated with previous exposure to (ACEi) and/or ARB). Methods MEDLINE, CENTRAL, PsycINFO, Web of Science Core Collection were searched in June 2020 for controlled studies. Eligible studies were included and random-effects meta-analyses were performed. The estimates were expressed as odds ratios (OR) and 95% confidence intervals (95%CI). Heterogeneity was assessed with I 2 test. The confidence in the pooled evidence was appraised using the GRADE framework. Results Twenty-seven studies were included in the review. ACEi/ARB exposure did not increase the risk of having a positive test for COVID-19 infection (OR 0.99, 95%CI 0.89–1.11; I 2 = 36%; 5 studies, GRADE confidence moderate). The exposure to ACEi/ARB did not increase the risk of all-cause mortality among patients with COVID-19 (OR 0.91, 95%CI 0.74–1.11; I 2 = 20%; 17 studies; GRADE confidence low) nor severe/critical COVID-19 disease (OR 0.90, 95%CI 0.74–1.11; I 2 = 55%; 17 studies; GRADE confidence very low). Exploratory analyses in studies enrolling hypertensive patients showed a association of ACEi/ARB with a significant decrease of mortality risk. Conclusions ACEi/ARB exposure does not seem to increase the risk of having the SARS-CoV-2 infection or developing severe stages of the disease including mortality. The potential benefits observed in mortality of hypertensive patients reassure safety, but robust studies are required to increase the confidence in the results.

The use of renin–angiotensin–aldosterone system (RAAS) inhibitors is associated with a lower risk of mortality in hypertensive COVID‐19 patients: A systematic review and meta‐analysis

“…Administering recombinant soluble ACE‐2 or increasing soluble ACE‐2 in plasma was considered as a therapeutic strategy to inactivate SARS‐CoV‐2 42 . Second, previous retrospective cohort studies 43,44 showed RAAS inhibitors do not increase the susceptibility of COVID‐19 45 . Finally, our meta‐analysis strongly suggested ACEI/ARB treatment was significantly associated with a lower risk of mortality in COVID‐19 infected hypertensive patients.…”

“…42 Second, previous retrospective cohort studies 43,44 showed RAAS inhibitors do not increase the susceptibility of COVID-19. 45 Finally, our meta-analysis strongly suggested should shed light on the effects of ACEI/ARB in different populations. Second, the duration of the included study was short.…”

Update Alert 7: Risks and Impact of Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers on SARS-CoV-2 Infection in Adults

“…Our confidence in this finding remains high after incorporating new evidence since the publication of our original review given the consistency of results across studies, representing adults from several geographic regions during different phases of the pandemic. Results are supported by several systematic reviews or meta-analyses ( 92–112 ).…”

“…New evidence since the publication of our original review includes results from a randomized controlled trial and 4 large database studies that included patients with a mix of disease severity ( 16–19 , 23 ). These studies consistently found that ACEI or ARB use was not associated with a higher risk for SARS-CoV-2 infection, findings which are further supported by 5 systematic reviews or meta-analyses ( 11 , 14 , 92–94 ). Because we consider these findings to be stable (meaning that future studies are likely to have the same results), we will no longer do literature surveillance on this KQ and will retire it from our living review.…”

The Effect of Chronic and Inhospital Exposure to Renin-Angiotensin System Inhibitors on the Outcome and Inflammatory State of Coronavirus Disease 2019 Adult Inpatients

“…Patoulias et al [ 15 ] showed that, although the use of RASi does not increase the odds for SARS-CoV-2-related death in a global scenario (OR = 1.06, 95% CI 0.77–1.47, I 2 = 83%), it increases the odds for death in Europe by 68% (OR = 1.68, 95% CI 1.05–2.70, I 2 = 82%), while decreasing it in Asia by 38% (OR = 0.62, 95% CI 0.39–0.99, I 2 = 0%). Others have come to the same nonsignificant results in a global perspective, but no subgroup analysis by region was made [ 16 ]. Our study indicates that RASi exposure is not associated with an increase nor decrease in the risk of inhospital all-cause mortality (adjusted OR 0.66, 95% CI 0.31–1.40, p =0.226), even though the odds showed a nonsignificant trend of decrease in the exposed group after adjusting for age and comorbidities (logistic regression coefficient of −0.42) ( Table 2 ).…”