Background Alteplase improves functional outcomes of patients with acute ischaemic stroke,but its effects on symptomatic infarct swelling,an adverse complication of stroke and the influence of CT hyperdense artery sig...Background Alteplase improves functional outcomes of patients with acute ischaemic stroke,but its effects on symptomatic infarct swelling,an adverse complication of stroke and the influence of CT hyperdense artery sign(HAS)are unclear.This substudy of the Third International Stroke Trial aimed to investigate the association between HAS and symptomatic infarct swelling and effect of intravenous alteplase on this association.Methods We included stroke patients whose prerandomisation scan was non-contrast CT.Raters,masked to clinical information,assessed baseline(prerandomisation)and follow-up(24-48 hours postrandomisation)CT scans for HAS,defined as an intracranial artery appearing denser than contralateral arteries.Symptomatic infarct swelling was defined as clinically significant neurological deterioration≤7 days after stroke with radiological evidence of midline shift,effacement of basal cisterns or uncal herniation.Results Among 2961 patients,HAS presence at baseline was associated with higher risk of symptomatic infarct swelling(OR 2.21;95% CI 1.42 to 3.44).Alteplase increased the risk of swelling(OR 1.69;95% CI 1.11 to 2.57),with no difference between patients with and those without baseline HAS(p=0.49).In patients with baseline HAS,alteplase reduced the proportion with HAS at follow-up(OR 0.67;95% CI 0.50 to 0.91),where HAS disappearance was associated with reduced risk of swelling(OR 0.25,95% CI 0.14 to 0.47).Conclusion Although alteplase was associated with increased risk of symptomatic infarct swelling in patients with or without baseline HAS,it was also associated with accelerated clearance of HAS,which in return reduced swelling,providing further mechanistic insights to underpin the benefits of alteplase.展开更多
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 eff...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.展开更多
基金the UK Medical Research Council(MRC G0400069 and EME-09-800-15)Other fundings are detailed in the Supplemental Material.SW acknowledges funding from the National Natural Science Foundation of China(81701156)+6 种基金GM acknowledges funding from the Stroke Association(SA L-SMP 18\1000)ML acknowledges funding from the Key Research and Development Program,Science&Technology Department of Sichuan Province(2017SZ0007)the Major International(Regional)Joint Research Project,National Natural Science Foundation of China(81620108009)the National Key Research and Development Program of China,Ministry of Science and Technology of China(2016YFC1300500-505)the 1.3.5 Project for Disciplines of Excellence,West China Hospital,Sichuan University(ZYGD18009)JMW acknowledges funding from the UK Dementia Research Institute(DRI Ltd:Medical Research Council,Alzheimer's Society and Alzheimer's Research UK),British Heart Foundation Centre for Research Excellence Award III(RE/18/5/34216)the Fondation Leducq(16 CVD 05).
文摘Background Alteplase improves functional outcomes of patients with acute ischaemic stroke,but its effects on symptomatic infarct swelling,an adverse complication of stroke and the influence of CT hyperdense artery sign(HAS)are unclear.This substudy of the Third International Stroke Trial aimed to investigate the association between HAS and symptomatic infarct swelling and effect of intravenous alteplase on this association.Methods We included stroke patients whose prerandomisation scan was non-contrast CT.Raters,masked to clinical information,assessed baseline(prerandomisation)and follow-up(24-48 hours postrandomisation)CT scans for HAS,defined as an intracranial artery appearing denser than contralateral arteries.Symptomatic infarct swelling was defined as clinically significant neurological deterioration≤7 days after stroke with radiological evidence of midline shift,effacement of basal cisterns or uncal herniation.Results Among 2961 patients,HAS presence at baseline was associated with higher risk of symptomatic infarct swelling(OR 2.21;95% CI 1.42 to 3.44).Alteplase increased the risk of swelling(OR 1.69;95% CI 1.11 to 2.57),with no difference between patients with and those without baseline HAS(p=0.49).In patients with baseline HAS,alteplase reduced the proportion with HAS at follow-up(OR 0.67;95% CI 0.50 to 0.91),where HAS disappearance was associated with reduced risk of swelling(OR 0.25,95% CI 0.14 to 0.47).Conclusion Although alteplase was associated with increased risk of symptomatic infarct swelling in patients with or without baseline HAS,it was also associated with accelerated clearance of HAS,which in return reduced swelling,providing further mechanistic insights to underpin the benefits of alteplase.
基金British Heart Foundation(grant number CS/14/4/30972)JPA is supported by an NIHR Health and Care Research Scholarship.PMB is Stroke Association Professor of Stroke Medicine and an NIHR Senior Investigator.TR is an NIHR Senior Investigator.GM is the Stroke Association Edith Murphy Foundation Senior Clinical Lecturer(SA L-SMP 18\1000).
文摘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.
