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.

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

doi:10.1016/j.eclinm.2022.101274

Abstract

SummaryBackgroundIt is not known whether to continue or temporarily stop existing antihypertensive drugs in patients with acute stroke.MethodsWe 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.FindingsOf 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.InterpretationIn 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.

Highlights

Treating hypertension is effective at preventing first and recurrent stroke.[1,2] As a result, many patients are taking blood pressure (BP)-lowering therapy at the time of any subsequent stroke
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
We explore in more detail functional and other outcomes, and potential explanations, in ENOS participants randomised within 12 h of stroke onset

Summary

Introduction

Treating hypertension is effective at preventing first and recurrent stroke.[1,2] As a result, many patients are taking blood pressure (BP)-lowering therapy at the time of any subsequent stroke. The multicentre Continue or Stop Post-Stroke Antihypertensives Collaborative Study (COSSACS) found that continuing antihypertensive drugs, as compared with stopping them, in 763 participants randomised within 48 h did not alter death or dependency at either two weeks or 6 months.[6] there was no difference in functional outcome in 2097 patients randomised within 48 h in the large Efficacy of Nitric Oxide in Stroke (ENOS) trial.[7] there were non-significant tendencies to a worse outcome in those patients randomised to continue prior antihypertensive agents within two pre-defined time windows, i.e. within 6 h, and between 6 and 12 h, of stroke onset.[7] When the two earlier time windows were pooled together, there was a positive interaction between time to randomisation (0 −12 hrs, 12−24 hrs, 24−48 hrs), randomisation to continue or stop pre-stroke antihypertensives and functional outcome (pinteraction=0.041). When examined in a meta-analysis of COSSACS and ENOS, worse functional outcome was seen in those randomised within 12 h (interaction between time to randomisation, randomised treatment and functional outcome p = 0.055).[8] Here, we explore in more detail functional and other outcomes, and potential explanations, in ENOS participants randomised within 12 h of stroke onset

Methods

Results

Conclusion