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Effect of continuing versus stopping pre-stroke antihypertensive agents within 12h on outcome after stroke: A subgroup analysis of the efficacy of nitric oxide in stroke (ENOS) trial

Woodhouse, Lisa J.; Appleton, Jason P.; Scutt, Polly; Everton, Lisa; Wilkinson, Gwenllian; Caso, Valeria; Czlonkowska, Anna; Gommans, John; Krishnan, Kailash; Laska, Ann C.; Ntaios, George; Ozturk, Serefnur; Phillips, Stephen; Pocock, Stuart; Prasad, Kameshwar; Szatmari, Szabolcs; Wardlaw, Joanna M.; Sprigg, Nikola; Bath, Philip M.

Effect of continuing versus stopping pre-stroke antihypertensive agents within 12h on outcome after stroke: A subgroup analysis of the efficacy of nitric oxide in stroke (ENOS) trial Thumbnail


Authors

Jason P. Appleton

Polly Scutt

Lisa Everton

Gwenllian Wilkinson

Valeria Caso

Anna Czlonkowska

John Gommans

Kailash Krishnan

Ann C. Laska

George Ntaios

Serefnur Ozturk

Stephen Phillips

Stuart Pocock

Kameshwar Prasad

Szabolcs Szatmari

Joanna M. Wardlaw

NIKOLA SPRIGG nikola.sprigg@nottingham.ac.uk
Professor of Stroke Medicine

PHILIP BATH philip.bath@nottingham.ac.uk
Stroke Association Professor of Stroke Medicine



Abstract

Background: It is not known whether to continue or temporarily stop existing antihypertensive drugs in patients with acute stroke. Methods: We performed a prospective subgroup analysis of patients enrolled into the Efficacy of Nitric Oxide in Stroke (ENOS) trial who were randomised to continue vs stop prior antihypertensive therapy within 12 h of stroke onset. The primary outcome was functional outcome, assessed with the modified Rankin Scale at 90 days by observers blinded to treatment assignment, and analysed with ordinal logistic regression. Findings: Of 4011 patients recruited into ENOS from 2001 to 2014, 2097 patients were randomised to continue vs stop prior antihypertensive treatment, and 384 (18.3%, continue 185, stop 199) were enrolled within 12 h of ictus: mean (SD) age 71.8 (11.8) years, female 193 (50.3%), ischaemic stroke 342 (89.1%) and total anterior circulation syndrome 114 (29.7%). As compared with stopping, continuing treatment within 12 h of onset lowered blood pressure by 15.5/9.6 mmHg (p<0.001/<0.001) by 7 days, shifted the modified Rankin Scale to a worse outcome by day 90, adjusted common odds ratio (OR) 1.46 (95% CI 1.01–2.11), and was associated with an increased death rate by day 90 (hazard ratio 2.17, 95% CI 1.24–3.79). Other outcomes (disability - Barthel Index, quality of life - EQ-visual analogue scale, cognition - telephone mini-mental state examination, and mood - Zung depression scale) were also worse with continuing treatment. Interpretation: In this pre-specified subgroup analysis of the large ENOS trial, continuing prior antihypertensive therapy within 12 h of stroke onset in a predominantly ischaemic stroke population was unsafe with worse functional outcome, disability, cognition, mood, quality of life and increased death. Future studies assessing continuing or stopping prior antihypertensives in the context of thrombectomy are awaited.

Citation

Woodhouse, L. J., Appleton, J. P., Scutt, P., Everton, L., Wilkinson, G., Caso, V., …Bath, P. M. (2022). Effect of continuing versus stopping pre-stroke antihypertensive agents within 12h on outcome after stroke: A subgroup analysis of the efficacy of nitric oxide in stroke (ENOS) trial. eClinicalMedicine, 44, Article 101274. https://doi.org/10.1016/j.eclinm.2022.101274

Journal Article Type Article
Acceptance Date Jan 17, 2022
Online Publication Date Jan 24, 2022
Publication Date Feb 1, 2022
Deposit Date Aug 17, 2022
Publicly Available Date Aug 17, 2022
Journal eClinicalMedicine
Electronic ISSN 2589-5370
Publisher Elsevier
Peer Reviewed Peer Reviewed
Volume 44
Article Number 101274
DOI https://doi.org/10.1016/j.eclinm.2022.101274
Keywords General Medicine
Public URL https://nottingham-repository.worktribe.com/output/10078524
Publisher URL https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(22)00004-9/fulltext

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