Angiotensin Converting Enzyme Inhibitors and Angiotensin Receptor Blockers and Mortality Among COVID-19 Patients: A Systematic Review and Meta-Analysis

Abstract

Background: Angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) are known to increase the expression of angiotensin converting enzyme 2 receptor, which has been shown to be the receptor for the acute severe respiratory syndrome coronavirus 2 (SARS-CoV-2). Areas of Uncertainty: Based on these observations, speculations raised the concerns that ACEIs/ARBs users would be more susceptible to SARS-CoV-2 infection and would be at higher risk for severe COVID-19 disease and death. Therefore, we systematically reviewed the literature and performed a meta-analysis of the association between prior use of ACEIs and ARBs and mortality due to COVID-19 disease. Data Sources: A comprehensive search of several databases from November 2019 to June 18, 2020 was conducted. The databases included Ovid MEDLINE(R) and Epub Ahead of Print, In-Process and Other Non-Indexed Citations and Daily, Ovid Embase, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, Web of Science, and Scopus. Medrxiv.org was also searched for unpublished data. Therapeutic Advances: Nine studies with a total of 18,833 patients infected with SARS-CoV-2 met our eligibility criteria. Prior use of ACEIs and/or ARBs was associated with reduced mortality among SARS-CoV-2-infected patients, with a pooled adjusted relative risk (aRR) from 6 studies of 0.63, 95% confidence interval (CI) (0.42–0.94) (I2 = 65%). Three studies reported separately on ACEIs or ARBs and their association with survival among SARS-CoV-2-infected patients, with a pooled adjusted relative risk of 0.78, 95% CI (0.58–1.04) (I2 = 0%) and 0.97, 95% CI (0.73–1.30) (I2 = 0%) respectively. The results of sensitivity analyses were consistent with the main analysis. Conclusion: Our meta-analysis suggests that use of ACEIs/ARBs is associated with a decreased risk of death among SARS-CoV-2-infected patients. This finding provides a reassurance to the public not to stop prescribed ACEIs/ARBs because of fear of severe COVID-19.

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...…”

“… 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.…”

COVID-19, the Pandemic of the Century and Its Impact on Cardiovascular Diseases

“…[ 320 , 321 ] Statins also reduce ox-LDL levels and NADPH oxidase activity, which decreases ROS generation by inhibiting NF-κB signaling pathway-associated transcription or by improving endothelial NO synthase coupling. [ 322 ] Like ACEIs and ARBs, [ 323 ] statin treatment also increases ACE2 expression. [ 324 ] Statins may exert similar anti-viral activity to that of ACEIs and ARBs by reducing Ang II availability and increasing Ang-(1–7) production.…”

An umbrella review and meta‐analysis of renin–angiotensin system drugs use and COVID‐19 outcomes

“…Considering the critical domains, most reviews were considered to have had a satisfactory technique for the statistical combination of results (n = 45, 95.7%) [4][5][6][17][18][19][20][21][22]59,60 and for assessing risk of bias (n = 38, 80.1%). [4][5][6]17,[19][20][21][22][23][25][26][27][28]30,31,[34][35][36][37][38][40][41][42][43][44][45][46][48][49][50][51][52][53][55][56][57]59,60 Less reviews were favourably considered in terms of accounting for risk of bias when interpreting and discussing the results (n = 32, 68.1%), with appropriate conduct of publication bias (n = 33...…”