Background Antiplatelet agents reduce recurrence after cerebral ischaemia but are not effective in all patients,in part because of treatment resistance.The primary aim was to assess the proportion of patients who are ...Background Antiplatelet agents reduce recurrence after cerebral ischaemia but are not effective in all patients,in part because of treatment resistance.The primary aim was to assess the proportion of patients who are insensitive to clopidogrel.The secondary aim was to assess the association between insensitivity to clopidogrel and recurrent cerebrovascular events.Methods Following written informed consent,independent patients with a recent non-cardioembolic ischaemic stroke or transient ischaemic attack,and taking clopidogrel,were enrolled.Platelet function was assessed with remote measurement of surface expression of P-selectin(CD62P)using commercial kits sensitive to aspirin or clopidogrel.Participants’general practitioners provided details on recurrent vascular events at least 90 days later.Data are mean(SD)and median[IQR].Resistance was defined as:aspirin median fluorescence(MF)>500 units,clopidogrel MF>860 units.Non-parametric descriptors and tests were used.Results 63 patients were recruited:mean age 64(13.7)years,women 47%.At baseline,59(95%)patients were taking clopidogrel alone with 3(5%)on combined clopidogrel and aspirin.Assessment of platelet surface P-selectin revealed:aspirin test 528[317,834],>50054.8%;clopidogrel test 429[303,656],>86011.3%.No participants on aspirin and clopidogrel showed aspirin resistance.Thirteen(20.6%)patients had a recurrent cerebrovascular event;those with an ischaemic stroke had a non-significantly higher baseline P-selectin using the clopidogrel test as compared with those with no recurrence:626[380,801]versus 406[265,609],p=0.08.Conclusions Remote measurement of platelet function assessed using the platelet surface expression of P-selectin is feasible.11%of patients taking clopidogrel showed resistance.No significant associations were noted between clopidogrel resistance and recurrent ischaemic events.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
文摘Background Antiplatelet agents reduce recurrence after cerebral ischaemia but are not effective in all patients,in part because of treatment resistance.The primary aim was to assess the proportion of patients who are insensitive to clopidogrel.The secondary aim was to assess the association between insensitivity to clopidogrel and recurrent cerebrovascular events.Methods Following written informed consent,independent patients with a recent non-cardioembolic ischaemic stroke or transient ischaemic attack,and taking clopidogrel,were enrolled.Platelet function was assessed with remote measurement of surface expression of P-selectin(CD62P)using commercial kits sensitive to aspirin or clopidogrel.Participants’general practitioners provided details on recurrent vascular events at least 90 days later.Data are mean(SD)and median[IQR].Resistance was defined as:aspirin median fluorescence(MF)>500 units,clopidogrel MF>860 units.Non-parametric descriptors and tests were used.Results 63 patients were recruited:mean age 64(13.7)years,women 47%.At baseline,59(95%)patients were taking clopidogrel alone with 3(5%)on combined clopidogrel and aspirin.Assessment of platelet surface P-selectin revealed:aspirin test 528[317,834],>50054.8%;clopidogrel test 429[303,656],>86011.3%.No participants on aspirin and clopidogrel showed aspirin resistance.Thirteen(20.6%)patients had a recurrent cerebrovascular event;those with an ischaemic stroke had a non-significantly higher baseline P-selectin using the clopidogrel test as compared with those with no recurrence:626[380,801]versus 406[265,609],p=0.08.Conclusions Remote measurement of platelet function assessed using the platelet surface expression of P-selectin is feasible.11%of patients taking clopidogrel showed resistance.No significant associations were noted between clopidogrel resistance and recurrent ischaemic events.
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.
