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

Mackey, Katherine; King, Valerie; Gurley, Susan B.; Kiefer, Michael; Liederbauer, Erik; Vela, Kathryn; Sonnen, Payten; Kansagara, Devan

doi:10.7326/m20-1515

Cited by 119 publications

(158 citation statements)

References 42 publications

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“…Interestingly, mortality was slightly reduced (11%) in ACEIs/ARBs users of SARS-CoV-2 positive patients compared to those not using these medications although it was statistically insigni cant. These ndings are consistent in line with other analyses carried out by independent researchers 10,11 . Most importantly, the ndings of current analysis support different professional societies recommendations for continuing ACEIs/ARBs irrespective whether it is contraindicated for other clinical conditions not just COVID-19 reason 1 .…”

Section: Discussionsupporting

confidence: 93%

“…Another systematic review conducted by Mackey K et al 2020 reported the association of ACEIs/ARBs users versus non-ACEIs/ARBs users with SARS-CoV-2 test positivity in limited perspectives 11 . However, severity of COVID-19 illness was not reported for the patients with or without ACEIs/ARBs users but was adjusted with other covariates in this analysis, which certainly renders lacking robust evidence regarding these con icts.…”

Section: Introductionmentioning

confidence: 99%

“…However, severity of COVID-19 illness was not reported for the patients with or without ACEIs/ARBs users but was adjusted with other covariates in this analysis, which certainly renders lacking robust evidence regarding these con icts. Most importantly, this analysis used majority of the data from preprint articles which is not peer-reviewed making this analysis some concerns 11 .…”

Section: Introductionmentioning

confidence: 99%

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Association of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) with risk of mortality, severity or SARS-CoV-2 test positivity in COVID-19 patients: A systematic review and meta-analysis

Biswas

Kali

2020

Preprint

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Abstract Effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) in the treatment of COVID-19 is highly debated. It was aimed to assess aggregated risk by investigating the association of ACEIs/ARBs users against non-users of ACEIs/ARBs with the risk of mortality or severe clinical manifestations or magnitude of SARS-CoV-2 test positivity in COVID-19 patients. Systematic literature search was carried out in different databases for eligible studies. The pooled relative risks (RRs) were measured using RevMan software where P<0.05 was set as statistical significance. In total, 10 studies were included in this analysis. After pooled estimation, it was demonstrated that SARS-CoV-2 positive patients taking ACEIs/ARBs were not associated with increased risk of mortality as compared to those not taking ACEIs/ARBs (RR 0.89; 95% CI 0.64-1.23; P=0.48). Further, the risk of composite severe clinical manifestations was not found significantly different between the positive patients with or without ACEIs/ARBs users (RR 1.29; 95% CI 0.81-2.04; P=0.28). There was no risk difference for SARS-CoV-2 test positivity in patients with or without ACEIs/ARBs users (RR 1.00; 95% CI 0.95-1.05; P=0.91). These findings may augment current professional society guidelines for not discontinuing ACEIs/ARBs in treating COVID-19 patients where it is clinically indicated.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Association of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) with risk of mortality, severity or SARS-CoV-2 test positivity in COVID-19 patients: A systematic review and meta-analysis

Biswas

Kali

2020

Preprint

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“…We complemented an amended [8] meta-analysis and a living systematic review [9,10] with an updated search through 7/4/2020 in the PubMed, Cochrane, and medRxiv.org databases. A PRISMA owchart is shown in Figure S1 in the supplementary section.…”

Section: Methodsmentioning

confidence: 99%

Mortality, Severity, and Hospital Admission Among COVID-19 Patients with ACEI/ARB Use: A Meta-analysis Stratifying Countries Based on Response to the First Wave of the Pandemic

Alamer

Almulhim

Alrashed

et al. 2020

Preprint

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BackgroundThe use of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin receptor blockers (ARB) is controversial for treating COVID-19 patients. We aimed to estimate pooled risks of mortality, disease severity, and hospitalization associated with ACEI/ARB use and stratify them by country and country clusters. MethodsWe conducted a search in various databases through 7/4/2020 and then applied random-effects models to estimate pooled risks (ORp) across stratifications by country cluster. Clusters were chosen to reflect outbreak times (China followed by Korea/Italy, others subsequently) and mobility restrictions (China and Denmark/France/Spain with stricter lockdowns than the UK/US). ResultsOverall analysis showed no increase in mortality; however, a statistical increase in mortality was seen in the US/UK cluster with ORp=1.28[95%CI=1.04; 1.56] and a decrease in China with ORp=0.65[95%CI=0.43; 0.96] and France with OR=0.31[95%CI=0.14; 0.69]. Severity and hospitalization were not statistically significant in the analysis; however, several associations were seen in specific countries but not in country clusters. ConclusionThe country-cluster meta-analysis provided a reasonable explanation for COVID-19 mortality among ACEI/ARB users. The analysis did not explain differences in severity and suggested the involvement of other factors. Hospitalization findings may be considered informative as they may have been subjected to clinical decisions and hospital-bed availability.

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“…The foremost hypotheses describing the pathway through which SARS-CoV-2 enters the cells is related to the involvement of angiotensin-converting enzyme-2 (ACE2). Although this enzyme has been described as the receptor for coronaviruses [ 4 ], upregulation of ACE2 due to ACE inhibitors (ACEIs) or angiotensin receptor blockers (ARBs) has not been consistently demonstrated in human and animal studies (reported in [ 5 ]). ACE2 serves a counterbalancing role in the renin–angiotensin–aldosterone system (RAAS), i.e., it cleaves away (i) phenylalanine from angiotensin (Ang) II, converting it to Ang-(1-7), and (ii) leucine from Ang I, converting it to Ang-(1-9).…”

Section: Introductionmentioning

confidence: 99%

The Efficacy of the Mineralcorticoid Receptor Antagonist Canrenone in COVID-19 Patients

Vicenzi

Ruscica

Iodice

et al. 2020

JCM

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Background: In COVID-19 patients, aldosterone via angiotensin-converting enzyme-2 deregulation may be responsible for systemic and pulmonary vasoconstriction, inflammation, and oxidative organ damage. Aim: To verify retrospectively the impact of the mineralcorticoid receptor antagonist canrenone i.v. on the need of invasive ventilatory support and/or all-cause in-hospital mortality. Methods: Sixty-nine consecutive COVID-19 patients, hospitalized for moderate to severe respiratory failure at Fondazione Istituti di Ricovero e Cura a Carattere Scientifico (IRCCS) Ca’ Granda Ospedale Maggiore Policlinico of Milan, received two different therapeutic approaches in usual care according to the personal skills and pharmacological management experience of the referral medical team. Group A (n = 39) were given vasodilator agents or renin–angiotensin–aldosterone system (RAAS) inhibitors and group B (n = 30) were given canrenone i.v. Results: Among the 69 consecutive COVID-19 patients, those not receiving canrenone i.v. (group A) had an event-free rate of 51% and a survival rate of 64%. Group B (given a mean dose of 200 mg/q.d. of canrenone for at least two days of continuous administration) showed an event-free rate of 80% with a survival rate of 87%. Kaplan–Meier analysis for composite outcomes and mortality showed log rank statistics of 0.0004 and 0.0052, respectively. Conclusions: The novelty of our observation relies on the independent positive impact of canrenone on the all-cause mortality and clinical improvement of COVID-19 patients ranging from moderate to severe diseases.

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

Cited by 119 publications

References 42 publications

Association of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) with risk of mortality, severity or SARS-CoV-2 test positivity in COVID-19 patients: A systematic review and meta-analysis

Association of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin-receptor blockers (ARBs) with risk of mortality, severity or SARS-CoV-2 test positivity in COVID-19 patients: A systematic review and meta-analysis

Mortality, Severity, and Hospital Admission Among COVID-19 Patients with ACEI/ARB Use: A Meta-analysis Stratifying Countries Based on Response to the First Wave of the Pandemic

The Efficacy of the Mineralcorticoid Receptor Antagonist Canrenone in COVID-19 Patients

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