key: cord-0834721-wa3yw8c1 authors: Alamer, Ahmad; Abraham, Ivo title: Mortality in COVID-19 patients treated with ACEIs/ARBs: re-estimated meta-analysis results following the Mehra et al. retraction date: 2020-06-30 journal: Pharmacol Res DOI: 10.1016/j.phrs.2020.105053 sha: b49f49af6ca5951f11d0d2672babc654d4448637 doc_id: 834721 cord_uid: wa3yw8c1 • A meta-analysis included a retracted study for Covid-19 patients on ACEI/ARBs. • Re-estimation of that meta-analysis confirms there is no increase in mortality. • As more studies accrue, a “living systematic review” is needed to update risk estimates.  As more studies accrue, a "living systematic review" is needed to update risk estimates. Keywords: ACEI/ARBs, Covid-19, Mortality, Meta-analysis, Hypertension Sir, The scientific and clinical communities are still reeling from the sudden retraction by the New England Journal of Medicine [1, 2] and The Lancet [3, 4] of coronavirus disease 2019 (Covid-19) papers by Mehra et al. The ripple effects of these retractions extend widely and include an otherwise important meta-analysis by Zhang and colleagues [5] Research before the recent retractions. Of specific concern are the Mehra et al. [1] mortality data on angiotensin converting enzyme inhibitors (ACEI) and angiotensin-II-receptor blockers (ARB) and mortality in Covid-19 patients. We re-estimated the Zhang et al. [5] pooled estimates for mortality in Covid-19 patients and mortality in Covid-19 patients with antihypertensive indication after excluding the Mehra et al. [1] data. These re-estimations are necessary not only because of the retracted data themselves but also because of the relative weight of the Mehra et al. [1] data in the meta-analyses and the high heterogeneity observed in these analyses. Our re-estimations were performed using R Core Team (2020) (R Foundation for Statistical Computing, Vienna, Austria) and applied random effects models. Because of differences in the software packages used [6] , small differences may be observed that may be real or may be due to computation and rounding. The encouraging conclusion is that, apart from a small discrepancy between our re-estimations and the original Zhang et al. [5] results, there is no statistically significant mortality risk signal in Covid-19 patients receiving ACEI/ARB therapy -and this from a set of studies with much lower heterogeneity. Similarly, there is no statistically significant mortality risk signal in Covid-19 patients with the anti-hypertensive indication. However, caution is advised because excluding the Mehra et al. [1] study reduced the number of Covid-19 patients in the re-estimation by 1326 (61%), including 54 deaths. Hence the risk estimates reported her must be considered preliminary and indicative. More primary observational studies and safety trials are necessary, the results of which should subsequently be included in a "living systematic review" that updates the mortality risk estimates as data from more studies accrue [7] . Authors' contributions: I.A. conceived the idea and A.A. extracted all the data from the relevant articles and performed the statistical analysis for this letter. Both I.A. and A.A. discussed and verified the accuracy of the presented data against the published studies, and jointly drafted the manuscript. Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19 Retraction: Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19 Retraction-Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis RETRACTED: Hydroxychloroquine or chloroquine with or without a macrolide for treatment of COVID-19: a multinational registry analysis ACEI/ARB use and risk of infection or severity or mortality of COVID-19: A systematic review and meta-analysis How to perform a meta-analysis with R: a practical tutorial Living systematic reviews This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. The authors declare no competing interests. We would like to thank Zhang and colleagues for their meta-analysis. Our letter is intended to supplement their analysis.