Update Alert 7: Risks and Impact of Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers on SARS-CoV-2 Infection in Adults

Mackey, Katherine; Kansagara, Devan; Vela, Kathryn

doi:10.7326/l20-1446

Cited by 10 publications

(7 citation statements)

References 96 publications

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“…Whilst the withdrawal of these agents does not appear to worsen the course of COVID-19 disease, the addition of RAS blockade may yet improve outcomes due to factors such as presence of blockade at the time of infection, pharmacokinetic wash-out time, and physiological time to response. There is currently no randomised evidence for the effect of the initiation of ARBs on the course of disease in participants with newly diagnosed COVID-19 disease [ 27 ]. CLARITY is one of 12 trials registered on ClinicalTrials.gov (as of March 18 2021) that will test this hypothesis.…”

Section: Discussionmentioning

confidence: 99%

Protocol for the Controlled evaLuation of Angiotensin Receptor blockers for COVID-19 respIraTorY disease (CLARITY): a randomised controlled trial

Hockham

Kotwal

Wilcox

et al. 2021

Trials

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Background SARS-CoV-2 binds to membrane-bound angiotensin-converting enzyme 2 (ACE2) which may result in downregulation of membrane-bound ACE2. ACE2 is a key regulator of the renin-angiotensin system (RAS) and is responsible for degrading angiotensin II and thereby counteracting its pro-inflammatory, pro-fibrotic effects mediated through the angiotensin II type 1 receptor (AT1R). As AT1R is directly blocked by angiotensin receptor blockers (ARBs), these agents may offer a safe, low-cost solution for reducing COVID-19 respiratory outcomes. Methods and discussion CLARITY is a pragmatic, adaptive, two-arm, multi-centre, comparative effectiveness phase III randomised controlled trial that examines whether ARBs reduce COVID-19 severity among high-risk patients. Recruiting in India and Australia, the trial will compare treatment with a maximum tolerated daily dose of an ARB to standard of care. Treatment allocation is blinded in India but open-label in Australia due to interruptions to placebo supply in the latter. The primary endpoint is a 7-point ordinal scale of clinical states, ranging from no limitation of activities (category 1) to death (category 7), assessed on day 14. Secondary outcomes include the 7-point scale assessed at day 28 and 28- and 90-day mortality. The design adapts the sample size based on accumulating data via frequent interim analyses and the use of predictive probability to determine whether the current sample size is sufficient or continuing accrual would be futile. The trial commenced recruitment on 18 August 2020. Trial registration ClinicalTrials.gov, NCT04394117. Registered on 19 May 2020. Clinical Trial Registry of India: CTRI/2020/07/026831)

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Section: Discussionmentioning

confidence: 99%

Protocol for the Controlled evaLuation of Angiotensin Receptor blockers for COVID-19 respIraTorY disease (CLARITY): a randomised controlled trial

Hockham

Kotwal

Wilcox

et al. 2021

Trials

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“…Whether this applies to migraineurs with acute COVID-19 is unknown. Animal studies raised theoretical concerns that ACE inhibitors and angiotensin receptor blockers (ARBs) may worsen infection, by up-regulation of ACE receptors promoting COVID-19 attachment to host membranes [ 48 ]. There are no sound human data to recommend avoiding these agents as a preventive treatment for migraine, and stopping them in those with co-morbid hypertension may cause harm.…”

Section: Preventive Treatment (Migraine Prophylaxis)-(table 2 )mentioning

confidence: 99%

Navigating migraine care through the COVID-19 pandemic: an update

Angus‐Leppan

Guiloff

Benson³

et al. 2021

J Neurol

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The worldwide treatment gap for migraine before COVID-19 inevitably widens as attention focuses on an international emergency. Migraine hits people particularly in their early and middle years, potentially reduces quality of life and productivity, and remains a common emergency presentation. This article examines the impact of COVID-19 on migraine, and changing aspects of migraine care during and after the pandemic. Many risk factors for severe COVID-19-older age, male gender, cardiac and respiratory diseases, diabetes, obesity, and immunosuppression-are less frequent in migraineurs. Telemedicine is effective for migraine follow-up, and needs ongoing evaluation. Most migraine treatments can start or continue in acute COVID-19, with care to avoid drug interactions. Close contact procedures (botulinum toxin, acupuncture and steroid injections) are avoided in lockdown or in the vulnerable. Secondary effects of COVID-19, including long COVID and its economic impact, are probably equal or greater in people with migraine. Migraine and other long-term conditions need adequate resourcing to prevent personal, social and economic suffering. Treating migraine, a sequel of COVID, potentially reduces the impact of long COVID.

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“…Ideally, we would have larger randomized trials to address these gap. The recently completed trials and prior observational investigations have generally found no association between users of an ARB/ ACEI vs. non-ARB/ACEI and COVID-19-related outcomes [12]. However, in contrast to the prior analyses largely conducted among inpatients or those with and without COVID-19, the current analysis identified a significant 15% reduction in all-cause hospitalization or mortality among SARS-CoV-2-positive outpatients with hypertension taking ARB/ACEI-vs. non-ARB/ ACEI-based regimens.…”

Section: Plos Onementioning

confidence: 98%

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Update Alert 7: Risks and Impact of Angiotensin-Converting Enzyme Inhibitors or Angiotensin-Receptor Blockers on SARS-CoV-2 Infection in Adults

Cited by 10 publications

References 96 publications

Protocol for the Controlled evaLuation of Angiotensin Receptor blockers for COVID-19 respIraTorY disease (CLARITY): a randomised controlled trial

Protocol for the Controlled evaLuation of Angiotensin Receptor blockers for COVID-19 respIraTorY disease (CLARITY): a randomised controlled trial

Navigating migraine care through the COVID-19 pandemic: an update

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