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

Abstract

Background Conflicting findings and the analysis of unpublished and retracted data have led to controversy on the safety of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in people with COVID-19 infection. This meta-analysis examined the association of prescription of angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) with the outcome from COVID-19. Methods A systematic search was conducted to find published studies that reported the outcome of COVID-19 in relation to prescription of ACEI or ARB. Two authors (MF and AD) independently screened and extracted data and assessed study quality and strength of association using standardised tools. The endpoints for the meta-analyses were severe or critical disease outcome and mortality based on standardised criteria. Results Twenty-six studies including 8389 people prescribed ACEI or ARB and 20,989 people not prescribed these medications were included. The quality of studies varied, and the overall strength of association was poor with a high risk of confounding bias. Patients prescribed ACEI or ARB had a greater prevalence of risk factors. Meta-analysis found an association between prescription of ACEI or ARB with severe or critical disease outcome (risk ratio, RR, 1.23, 95% confidence interval, CI, 1.06 to 1.42, p = 0.006, I2 = 88%) but this association was lost in sensitivity analyses. There was no association between ACEI or ARB prescription and mortality (RR 1.18, 95% CI 0.92 to 1.50, p = 0.19, I2 = 82%). Conclusions This meta-analysis suggests that people prescribed ACEI or ARB more commonly had severe or critical disease outcome, but not mortality, in published cohorts of patients diagnosed with COVID-19. This finding is most likely due to a greater prevalence of risk factors in these patients rather than due to exposure to angiotensin pathway inhibitors.

Renin‐Angiotensin Aldosterone System Inhibitors and COVID‐19: A Systematic Review and Meta‐Analysis Revealing Critical Bias Across a Body of Observational Research

“…This study was not the first systematic review and meta‐analysis to assess the associations between RAAS inhibitor use and COVID‐19 outcomes. As of December 2021, at least 52 meta‐analyses had been conducted, 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 each of which pooled studies that have a critical risk of bias. Critical biases limit confidence in the evidence produced by these meta‐analyses as much as they do in each of the studies that t...…”

“… 242 However, only six of the 52 previous meta‐analyses followed current guidelines and used the ROBINS‐I to assess risk of bias. 16 , 21 , 28 , 35 , 36 , 39 It is unclear as to why the authors of five of those six studies did not identify any critical risks of bias and proceeded with their meta‐analyses. One meta‐analysis, however, deviated from the guidelines, establishing their own unstandardized scoring system for the ROBINS‐I.…”

“…One meta‐analysis, however, deviated from the guidelines, establishing their own unstandardized scoring system for the ROBINS‐I. 21 …”

“… 6 At least 52 meta‐analyses have assessed associations between RAAS inhibitor use and COVID‐19 risk by collating parts of that body of research. 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 , 25 , 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 , 35 , 36 , 37 , 38 , 39 , 40 , 41 , 42 , 43 , 44 , 45 , 46 , 47 , 48 , 49 , 50 , 51 , 52 , 53 , 54 , 55 , 56 , 57 , 58 However, little attention has been paid to selection bias, or other biases for that matter, which may distort the interaction between RAAS inhibitor use and COVID‐19.…”

The use of renin-angiotensin system blockers in patients with COVID-19

“…Не выявлено связи между назначением блокаторов РАС и смертностью (ОР 1,18, 95% ДИ 0,92-1,50; p=0,19, I 2 =82%). Полученные результаты авторы связывают с большей распространенностью факторов риска у пациентов, получавших ИАПФ и БРА, а не с собственным влиянием блокаторов РАС на течение болезни [16].…”