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. 2022 Jan 24:44:101274.
doi: 10.1016/j.eclinm.2022.101274. eCollection 2022 Feb.

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

Lisa J Woodhouse  1 , Jason P Appleton  2   3 , Polly Scutt  1 , Lisa Everton  1   4 , Gwenllian Wilkinson  1   4 , Valeria Caso  5 , Anna Czlonkowska  6 , John Gommans  7 , Kailash Krishnan  4 , Ann C Laska  8 , George Ntaios  9 , Serefnur Ozturk  10 , Stephen Phillips  11 , Stuart Pocock  12 , Kameshwar Prasad  13 , Szabolcs Szatmari  14 , Joanna M Wardlaw  15 , Nikola Sprigg  1   4 , Philip M Bath  1   4 ; ENOS Investigators
Affiliations

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

Lisa J Woodhouse et al. EClinicalMedicine. .

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.

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Conflict of interest statement

JPA was supported in part by National Institute of Health Research (NIHR) TARDIS (10/104/24) and British Heart Foundation RIGHT-2 (CS/14/4/30972) and is supported by a NIHR Health and Care Research Scholarship. JMW was supported, in part, by the Scottish Funding Council through the SINAPSE Collaboration and the UK Dementia Research Institute which receives funding from DRI Ltd, funded by the UK Medical Research Council, Alzheimer's Society and Alzheimer's Research UK. PMB is Stroke Association Professor of Stroke Medicine and a NIHR Senior Investigator. All other authors report no declarations.

Figures

Fig 1
Figure 1
Comparison in distribution of seven-level modified Rankin Scale between continue versus stop prior antihypertensives at day 90. Continuing prior antihypertensives was associated with a worse functional outcome, adjusted common odds ratio 1.46 (95% CI 1.01–2.11, p = 0.044), unadjusted common odds ratio 1.56 (95% CI 1.09–2.22, p = 0.015).
Fig 2
Figure 2
Subgroup analysis of effects on functional outcome at 90 days for continue versus stop prior antihypertensives for patients enrolled within 12 h of stroke onset. Ordinal logistic regression was used to produce odds ratios with 95% confidence intervals for each subgroup. Two-sided p values are for the interaction between subgroup and allocated treatment. OCSP: Oxfordshire Community Stroke Project. Significant interactions were present for stroke severity (severe vs moderate/mild) and feeding (non-oral vs oral).
Fig 3
Figure 3
Survival curves over the 90 days of follow-up: continue versus stop prior antihypertensives. Continuing prior antihypertensives was associated with increased death: hazard ratio 2.17 (95% confidence interval 1.24–3.79; p = 0.007).
See this image and copyright information in PMC

References

    1. Neal B., MacMahon S., Chapman N. Blood pressure lowering treatment trialists C. effects of ACE inhibitors, calcium antagonists, and other blood-pressure-lowering drugs: results of prospectively designed overviews of randomised trials. blood pressure lowering treatment trialists' collaboration. Lancet. 2000;356(9246):1955–1964. - PubMed
    1. Rashid P., Leonardi-Bee J., Bath P. Blood pressure reduction and the secondary prevention of stroke and other vascular events: a systematic review. Stroke. 2003;34:2741–2749. - PubMed
    1. Lees K.R., Dyker A.G. Blood pressure control after acute stroke. J Hypertens. 1996;14(suppl 6):S35–SS8. - PubMed
    1. Bath P.M.W., Weaver C., Iddenden R., Bath F.J. A trial of blood pressure reduction in acute stroke. Age Ageing. 2000;29:554–555. - PubMed
    1. Royal College of Physicians . National Clinical Guidelines for Stroke. 5th ed. Royal College of Physicians; 2016. Intercollegiate stroke working party.