No benefit of flat head positioning in early moderate-severe acute ischaemic stroke: a HeadPoST study subgroup analysis

background Although the Head Positioning in acute Stroke Trial(HeadPoST)showed no effect of the flat head position(FP;vs sitting up head position(SUP))on functional outcome,we hypothesised that it could still offer benefits if commenced early in those with acute ischaemic stroke(AIS)of at least moderate severity.Methods Subgroup analysis of HeadPoST in participants with National Institutes of Health Stroke Scale(NIHSS)scores≥7,≥10 and≥14,randomised to FP or SUP<4.5 hours of AIS onset on functional outcomes defined by a shift in scores on the modified Rankin scale(mRS)and death/disability(mRS scores 3-6),and any cardiovascular serious adverse event.Logistic regression analyses were undertaken adjusted for study design and baseline risk factors.results There was no significant differential treatment effect in patient subgroups defined by increasing baseline NIHSS scores:adjusted OR and 95%CI for ordinal shift and binary(3-6)mRS scores:for NIHSS≥7(n=867)0.92(0.67 to 1.25)and 0.74(0.52 to 1.04);NIHSS≥10(n=606)0.80(0.58 to 1.10)and 0.77(0.49 to 1.19);NIHSS≥14(n=378)0.82(0.54 to 1.24)and 1.22(0.69 to 2.14).Conclusions Early FP had no significant effect in patients with moderate-severe AIS.

Prehospital transdermal glyceryl trinitrate for ultra- acute ischaemic stroke: data from the RIGHT- 2 randomised sham- controlled ambulance trial

Background The effect of transdermal glyceryl trinitrate(GTN,a nitrovasodilator)on clinical outcome when administered before hospital admission in suspected stroke patients is unclear.Here,we assess the safety and efficacy of GTN in the prespecified subgroup of patients who had an ischaemic stroke within the Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2(RIGHT-2).Methods RIGHT-2 was an ambulance-based multicentre sham-controlled blinded-endpoint study with patients randomised within 4hours of onset.The primary outcome was a shift in scores on the modified Rankin scale(mRS)at day 90.Secondary outcomes included death;a global analysis(Wei-Lachin test)containing Barthel Index,EuroQol-5D,mRS,telephone interview for cognitive status-modified and Zung depression scale;and neuroimaging-determined‘brain frailty’markers.Data were reported as n(%),mean(SD),median[IQR],adjusted common OR(acOR),mean difference or Mann-Whitney difference(MWD)with 95%CI.Results 597 of 1149(52%)patients had a final diagnosis of ischaemic stroke;age 75(12)years,premorbid mRS>2107(18%),Glasgow Coma Scale 14(2)and time from onset to randomisation 67[45,108]min.Neuroimaging‘brain frailty’was common:median score 2[2,3](range 0–3).At day 90,GTN did not influence the primary outcome(acOR for increased disability 1.15,95%CI 0.85 to 1.54),death or global analysis(MWD 0.00,95%CI-0.10 to 0.09).In subgroup analyses,there were non-significant interactions suggesting GTN may be associated with more death and dependency in participants randomised within 1hour of symptom onset and in those with more severe stroke.Conclusions In patients who had an ischaemic stroke,ultra-acute administration of transdermal GTN in the ambulance did not improve clinical outcomes in a population with more clinical and radiological frailty than seen in previous in-hospital trials.WHAT IS ALREADY KNOWN ON THIS TOPIC⇒Transdermal glyceryl trinitrate(GTN)was associat-ed with less death and dependency in those with acute stroke treated within 6hours of stroke onset in a systematic review and individual patient data meta-analysis from two randomised controlled tri-als.The Rapid Intervention with Glyceryl trinitrate in Hypertensive stroke Trial-2(RIGHT-2)assessed the effect of GTN given prehospital in patients with pre-sumed stroke within 4hours of onset.This subgroup analysis details the effect of GTN in those with clini-cally diagnosed ischaemic stroke.WHAT THIS STUDY ADDS⇒Transdermal GTN did not influence clinical or radio-logical outcomes despite lowering blood pressure compared with sham.GTN may be associated with more death and dependency in those randomised within 1hour of symptom onset and in those with more severe stroke,but these interactions were non-significant.The population recruited in RIGHT-2 was more dependent and frailer(both clinically and radiologically)than in prior trials of transdermal GTN within 6hours of stroke onset performed in hospital,and may account for the differences in results.HOW THIS STUDY MIGHT AFFECT RESEARCH,PRACTICE OR POLICY⇒Transdermal GTN should not be administered to pa-tients with presumed stroke prehospital outside of a trial environment.Clinical and radiological frailty should be taken into consideration in the design and interpretation of future ultra-acute stroke trials.