Impact of angiotensin-converting enzyme inhibitors and statins on viral pneumonia

Henry, Christopher; Zaizafoun, Manaf; Stock, Eileen M.; Ghamande, Shekhar; Arroliga, Alejandro C.; White, Heath

doi:10.1080/08998280.2018.1499293

Cited by 110 publications

(114 citation statements)

References 32 publications

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“…In addition, lower proportion of patients with COVID-19 overall were on ARBs or ACEIs than expected 27,28 raising the possibility that concerns regarding these drugs at the beginning of the epidemic may have resulted in change in medication in patients on admission, In-hospital use of ACEI has previously been shown to be associated with lower rate of ventilation and inhospital mortality with viral pneumonias. 29 Our case-control analysis showed that those taking CCBs had significantly increased risk [OR 1.67 (95% CI 1.2-2.9)] of manifesting symptoms of COVID-19. In addition, patients on beta-blockers were more likely to develop severe (13.2%) and critical form (21.1%) compared to mild/ common form (6.6%) of the disease but this last analysis was not significant after adjusting for age sex and BMI.…”

Section: (Which Was Not Certified By Peer Review)mentioning

confidence: 68%

Role of Drugs used for chronic disease management on Susceptibility and Severity of COVID-19: A Large Case-Control Study

Yan

Valdes

Vijay

et al. 2020

Preprint

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Background. Medical editorials have suggested that angiotensin converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) should not be given to people with arterial hypertension during the coronavirus disease 2019 pandemic because of a potential increased risk of worse clinical outcomes and that calcium channel blockers (CCBs) should be used as an alternative.Methods Using a cohort of 610 COVID-19 cases and 48,667 population-based controls from Zheijang, China we have tested the role of usage of ACEIs, ARBs, CCBs and other medications on risk and severity of COVID 19. Analyses were adjusted for age, sex and BMI and for presence of relevant comorbidities. Findings:Higher BMI, diabetes and cardio/ cerebrovascular disease are independent risk factors for the development of COVID-19. Individuals with hypertension taking CCBs had significantly increased risk [odds ratio (OR)= 1.67 (95% CI 1.2-2.9)) of manifesting symptoms of COVID-19 whereas those taking ARBs and diuretics had significantly lower disease risk (OR=0.24; 95%CI 0.17-0.34 and OR=0.32; 95%CI 0.19-0.57 respectively). Other antihypertensive drugs were not associated with increased . CC-BY-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review)

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Section: (Which Was Not Certified By Peer Review)mentioning

confidence: 68%

Role of Drugs used for chronic disease management on Susceptibility and Severity of COVID-19: A Large Case-Control Study

Yan

Valdes

Vijay

et al. 2020

Preprint

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“…Mice with coronavirus induced lung injury showed improvement when treated with losartan [39]. Moreover, a retrospective analysis found reduced rates of death and endotracheal intubation in patients with viral pneumonia who were continued on ACE inhibitors [40]. Treatment with ARBs was reported to reduce mortality in Ebola virus infection [41].…”

Section: Effects Of Ace Inhibitors and Angiotensin Receptor Blockersmentioning

confidence: 99%

Comorbidities in COVID-19: Outcomes in hypertensive cohort and controversies with renin angiotensin system blockers

Singh

Gupta

Misra

2020

Diabetes & Metabolic Syndrome: Clinical Research & Revi

222

156

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a b s t r a c tBackground and aims: COVID-19 is already a pandemic. Emerging data suggest an increased association and a heightened mortality in patients of COVID-19 with comorbidities. We aimed to evaluate the outcome in hypertensive patients with COVID-19 and its relation to the use of renin-angiotensin system blockers (RASB). Methods: We have systematically searched the medical database up to March 27, 2020 and retrieved all the published articles in English language related to our topic using MeSH key words. Results: From the pooled data of all ten available Chinese studies (n ¼ 2209) that have reported the characteristics of comorbidities in patients with COVID-19, hypertension was present in nearly 21%, followed by diabetes in nearly 11%, and established cardiovascular disease (CVD) in approximately 7% of patients. Although the emerging data hints to an increase in mortality in COVID-19 patients with known hypertension, diabetes and CVD, it should be noted that it was not adjusted for multiple confounding factors. Harm or benefit in COVID-19 patients receiving RASB has not been typically assessed in these studies yet, although mechanistically and plausibly both, benefit and harm is possible with these agents, given that COVID-19 expresses to tissues through the receptor of angiotensin converting enzyme-2. Conclusion: Special attention is definitely required in patients with COVID-19 with associated comorbidities including hypertension, diabetes and established CVD. Although the role of RASB has a mechanistic equipoise, patients with COVID-19 should not stop these drugs at this point of time, as recommended by various world organizations and without the advice of health care provider.

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“…A secondary analysis of a 2010 randomized control trial in patients with acute respiratory failure suggested that treatment with ACEi/ARB at discharge following an episode of acute respiratory failure was associated with a 44% reduction in 1-year mortality [81]. More recently, Hsieh et al85] and continuation of RAAS inhibitor therapy during admission is associated with decreased hospital mortality and odds of intubation in viral cases of pneumonia [86]. RAAS may have implications for other viral pneumonias, as well, as Gu et al found that children with respiratory syncytial virus tend to have higher Ang II levels compared to healthy children [87].…”

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confidence: 99%

Understanding the renin–angiotensin–aldosterone–SARS-CoV axis: a comprehensive review

et al. 2020

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ImportanceCoronavirus disease 2019 (COVID-19), the disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been declared a global pandemic with significant morbidity and mortality since first appearing in Wuhan, China, in late 2019. As many countries are grappling with the onset of their epidemics, pharmacotherapeutics remain lacking. The window of opportunity to mitigate downstream morbidity and mortality is narrow but remains open. The renin–angiotensin–aldosterone system (RAAS) is crucial to the homeostasis of both the cardiovascular and respiratory systems. Importantly, SARS-CoV-2 utilises and interrupts this pathway directly, which could be described as the renin–angiotensin–aldosterone–SARS-CoV (RAAS–SCoV) axis. There exists significant controversy and confusion surrounding how anti-hypertensive agents might function along this pathway. This review explores the current state of knowledge regarding the RAAS–SCoV axis (informed by prior studies of SARS-CoV), how this relates to our currently evolving pandemic, and how these insights might guide our next steps in an evidence-based manner.ObservationsThis review discusses the role of the RAAS–SCoV axis in acute lung injury and the effects, risks and benefits of pharmacological modification of this axis. There may be an opportunity to leverage the different aspects of RAAS inhibitors to mitigate indirect viral-induced lung injury. Concerns have been raised that such modulation might exacerbate the disease. While relevant preclinical, experimental models to date favour a protective effect of RAAS–SCoV axis inhibition on both lung injury and survival, clinical data related to the role of RAAS modulation in the setting of SARS-CoV-2 remain limited.ConclusionProposed interventions for SARS-CoV-2 predominantly focus on viral microbiology and aim to inhibit viral cellular injury. While these therapies are promising, immediate use may not be feasible, and the time window of their efficacy remains a major unanswered question. An alternative approach is the modulation of the specific downstream pathophysiological effects caused by the virus that lead to morbidity and mortality. We propose a preponderance of evidence that supports clinical equipoise regarding the efficacy of RAAS-based interventions, and the imminent need for a multisite randomised controlled clinical trial to evaluate the inhibition of the RAAS–SCoV axis on acute lung injury in COVID-19.

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Impact of angiotensin-converting enzyme inhibitors and statins on viral pneumonia

Cited by 110 publications

References 32 publications

Role of Drugs used for chronic disease management on Susceptibility and Severity of COVID-19: A Large Case-Control Study

Role of Drugs used for chronic disease management on Susceptibility and Severity of COVID-19: A Large Case-Control Study

Comorbidities in COVID-19: Outcomes in hypertensive cohort and controversies with renin angiotensin system blockers

Understanding the renin–angiotensin–aldosterone–SARS-CoV axis: a comprehensive review

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