Association of Angiotensin II Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors on COVID-19-Related Outcome

Lee, Hae Young; Ahn, Ji Hoon; Kang, Chang Kyung; Won, Sungho; Park, Jong-Heon; Kang, Cheong Hee; Chung, Ki-Hyun; Joh, Joon Sung; Bang, Jiwhan; Yoo, Hyuk Sang; Park, Ok; Oh, Myoung‐don

doi:10.2139/ssrn.3569837

Cited by 16 publications

(25 citation statements)

References 25 publications

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“…Two of us (SC and ADC) independently reviewed the studies identified, then jointly excluded the articles not adhering to one or both criteria, and agreed on a final selection of 18 studies [7,8,[17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32]. Findings from the CORIST project presented in this manuscript were also included in the meta-analyses, for a total of 19 studies.…”

Section: Methods Used For the Meta-analysismentioning

confidence: 99%

“…ǂ Lopinavir, darunavir, tocilizumab, sarilumab, corticosteroids or remdesivir considered as a unique group, missing data for N = 237 patients. [17,22,25,26]. The exposure to either ACE-I or ARB was analyzed separately or in combination, and was tested for association with mortality or a combined outcome of severe illness and mortality (Online Supplement Table 1).…”

Section: Tablementioning

confidence: 99%

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RAAS inhibitors are not associated with mortality in COVID-19 patients: Findings from an observational multicenter study in Italy and a meta-analysis of 19 studies

Castelnuovo¹,

Costanzo²,

Antinori³

et al. 2020

Vascular Pharmacology

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The hypothesis that been set forward that use of Renin Angiotensin Aldosterone System (RAAS) inhibitors is associated with COVID−19 severity. We setup a multicenter Italian collaboration (CORIST Project, ClinicalTrials.gov ID: NCT04318418) to retrospectively investigate the relationship between RAAS inhibitors and COVID−19 in-hospital mortality. We also carried out an updated meta-analysis on the relevant studies. Methods: We analyzed 4069 unselected patients with laboratory-confirmed SARS-CoV-2 infection and hospitalized in 34 clinical centers in Italy from February 19, 2020 to May 23, 2020. The primary end-point in a time-to event analysis was in-hospital death, comparing patients who received angiotensin-converting-enzyme inhibitors (ACEeI) or angiotensin-receptor blockers (ARB) with patients who did not. Articles for the meta-analysis were retrieved until July 13th, 2020 by searching in web-based libraries, and data were combined using the general variance-based method. Results: Out of 4069 COVID−19 patients, 13.5% and 13.3% received ACE-I or ARB, respectively. Use of neither ACE-I nor ARB was associated with mortality (multivariable hazard ratio (HR) adjusted also for COVID−19 treatments: 0.96, 95% confidence interval 0.77-1.20 and HR = 0.89, 0.67-1.19 for ACE-I and ARB, respectively). Findings were similar restricting the analysis to hypertensive (N = 2057) patients (HR = 1.00, 0.78-1.26 and HR = 0.88, 0.65-1.20) or when ACE-I or ARB were considered as a single group. Results from the meta-analysis (19 studies, 29,057 COVID−19 adult patients, 9700 with hypertension) confirmed the absence of association. Conclusions: In this observational study and meta-analysis of the literature, ACE-I or ARB use was not associated with severity or in-hospital mortality in COVID−19 patients.

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Section: Methods Used For the Meta-analysismentioning

confidence: 99%

Section: Tablementioning

confidence: 99%

RAAS inhibitors are not associated with mortality in COVID-19 patients: Findings from an observational multicenter study in Italy and a meta-analysis of 19 studies

Castelnuovo¹,

Costanzo²,

Antinori³

et al. 2020

Vascular Pharmacology

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“…The characteristics of the shortlisted studies are summarized in Table 1. Among shortlisted studies, 23 studies were from China , nine studies were from Italy [64][65][66][67][68][69][70][71][72], ten studies were from the United States [83][84][85][86][87][88][89][90][91][92], four studies were from South Korea [75][76][77][78], three studies were from France [60][61][62], two studies were from Spain [79,80], one study each was from Belgium [35], Denmark [59], Hong Kong [63], Kuwait [73], Singapore [74], Turkey [81], and the United Kingdom [82]; and one study included data from 38 countries [93]. There were 24 studies that included hypertensive patients exclusively (100%) [36, 38, 39, 43-45, 47, 48, 50-52, 54, 56, 58, 66, 71, 72, 75, 78, 81, 87-89, 91].…”

Section: Characteristics Of the Included Studiesmentioning

confidence: 99%

“…2; pooled OR = 0.73, 95% CI 0.56-0.95). In a separate pooled analysis of 11 studies that provided adjusted HRs, with 26,598 COVID-19 patients being analyzed [36,54,56,57,59,67,69,70,72,74,77], the use of an ACEI/ARB was significantly associated with lower risk of mortality compared to the non-use of an ACEI/ARB (Supplementary Figure S1; pooled HR = 0.75, 95% CI 0.60-0.95). The funnel plot was used to detect the publication bias and revealed some degree of asymmetry (Supplementary Figure S3 and S4).…”

Section: Characteristics Of the Included Studiesmentioning

confidence: 99%

Mortality and Disease Severity Among COVID-19 Patients Receiving Renin-Angiotensin System Inhibitors: A Systematic Review and Meta-analysis

Hasan

Kow

Hadi

et al. 2020

Am J Cardiovasc Drugs

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Introduction The use of renin-angiotensin system (RAS) inhibitors, including angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs), was alleged to cause a more severe course of novel coronavirus disease 2019 (COVID-19). Methods We systematically reviewed the published studies to assess the association of RAS inhibitors with mortality as well as disease severity in COVID-19 patients. A systematic literature search was performed to retrieve relevant original studies investigating mortality and severity (severe/critical disease) in COVID-19 patients with and without exposure to RAS inhibitors. Results A total of 59 original studies were included for qualitative synthesis. Twenty-four studies that reported adjusted effect sizes (24 studies reported mortality outcomes and 16 studies reported disease severity outcomes), conducted in RAS inhibitor-exposed and unexposed groups, were pooled in random-effects models to estimate overall risk. Quality assessment of studies revealed that most of the studies included were of fair quality. The use of an ACEI/ARB in COVID-19 patients was significantly associated with lower odds (odds ratio [OR] = 0.73, 95% confidence interval [CI] 0.56-0.95; n = 18,749) or hazard (hazard ratio [HR] = 0.75, 95% CI 0.60-0.95; n = 26,598) of mortality compared with non-use of ACEI/ARB. However, the use of an ACEI/ARB was non-significantly associated with lower odds (OR = 0.91, 95% CI 0.75-1.10; n = 7446) or hazard (HR = 0.73, 95% CI 0.33-1.66; n = 6325) of developing severe/critical disease compared with non-use of an ACEI/ARB. Discussion Since there was no increased risk of harm, the use of RAS inhibitors for hypertension and other established clinical indications can be maintained in COVID-19 patients.

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“…After screening 343 citations, 13 observational studies were included (Figure 1) [18][19][20][21][22][23][24][25][26][27][28][29][30], combining to a total sample of 14,364 participants. The characteristics of included studies are summarized in Table 1.…”

Section: Resultsmentioning

confidence: 99%

Renin-angiotensin system inhibitors and severity of SARS-CoV-2 infection: a meta-analysis

Oscanoa

Vidal

Carvajal

et al. 2020

Preprint

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Introduction The mechanism of entry of SARS-CoV-2 into the human host cell is through the ACE2 receptor. During the pandemic, a hypothesis has been proposed that Angiotensin-converting enzyme inhibitors (ACEi) and Angiotensin II receptor blockers (ARBs) could be risk factors for the development of severe SARS-CoV-2 infection. Objective To conduct a meta-analysis of the association between ACEi or ARB use and SARS-CoV-2 infection severity or mortality.Data Sources We searched PubMed, EMBASE, Google scholar and the Cochrane Database of Systematic Reviews for observational studies published between December 2019 and April 24, 2020Study Selection: Studies were included if they contained data on ACEi or ARB use and SARS-CoV-2 infection severity or mortality. Effect statistics were pooled using random-effects models. The quality of included studies was assessed with the Newcastle–Ottawa Scale (NOS). Data ExtractionData on study design, study location, year of publication, study design, number of participants, sex, age at baseline, outcome definition, exposure definition, follow-up, effect estimates and 95% Cis.Results Thirteen observational studies were identified for inclusion, combining to a total sample of 14364 participants. Mean age was 59.2 (SD 7.3) years and 53.5% were men. Mean follow-up was 28.3 (14.2) days. The mean NOS score of included studies was 7.8 (range: 7-9). Results suggested that ACEi or ARB use did not increase the risk of severe disease or mortality from SARS-CoV-2 infection (OR=0.72, 95% CI 0.47-1.11, p= 0.138).ConclusionsAt present, the limited evidence available does not support the hypothesis of increased SARS-CoV-2 risk with ACEi or ARB drugs. However, more evidence needs to accumulate before this controversy can be resolved.

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Association of Angiotensin II Receptor Blockers and Angiotensin-Converting Enzyme Inhibitors on COVID-19-Related Outcome

Cited by 16 publications

References 25 publications

RAAS inhibitors are not associated with mortality in COVID-19 patients: Findings from an observational multicenter study in Italy and a meta-analysis of 19 studies

RAAS inhibitors are not associated with mortality in COVID-19 patients: Findings from an observational multicenter study in Italy and a meta-analysis of 19 studies

Mortality and Disease Severity Among COVID-19 Patients Receiving Renin-Angiotensin System Inhibitors: A Systematic Review and Meta-analysis

Renin-angiotensin system inhibitors and severity of SARS-CoV-2 infection: a meta-analysis

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