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

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Stroke & Vascular Neurology 2024年第1期9卷 38-49,I0035-I0046页

作者： Jason philip Appleton Lisa J Woodhouse Craig S Anderson Sandeep Ankolekar Lesley Cala mark Dixon Timothy J England Kailash Krishnan Grant mair Keith W muir John Potter Christopher I Price marc Randall Thompson G Robinson Christine Roffe Else C Sandset Jeffrey L Saver Angela Shone Aloysius Niroshan Siriwardena Joanna m Wardlaw Nikola Sprigg philip m bath Stroke University Hospitals Birmingham NHS Foundation TrustBirminghamUK Institute of Applied HealthResearch University of Birmingham College of Medical and Dental SciencesBirminghamUK Stroke Trials Unit Mental Health and Clinical NeurosciencesUniversity of NottinghamNottinghamUK Faculty of medicine The George Institute for Global HealthSydneyNew South WalesAustralia The George Institute China at Peking University Health Science Center BeijingChina Neurology Royal Prince Alfred HospitalSydney Health PartnersSydneyNew South WalesAustralia Department of Neurology King's College Hospital NHS Foundation TrustLondonUK Faculty of Health and medical Sciences University of Western AustraliaCrawleyWestern AustraliaAustralia East midlands Ambulance Service NHS Trust NottinghamUK Stroke Queen's Medical CentreNottingham University Hospitals NHS TrustNottinghamUK Centre for Clinical Brain Sciences Dementia Research InstituteUniveristy of EdinburghEdinburghUK Institute of Neurology and Psychology University of GlasgowGlasgowUK Bob Champion Research and Education Building University of East AngliaNorwichUK Institute of Neuroscience Newcastle UniversityNewcastle upon TyneUK Department of Neurology Leeds Teaching Hospitals NHS TrustLeedsUK Department of Cardiovascular Sciences and NIHR Leicester Biomedical Research Centre University of LeicesterLeicesterUK Stroke Research in Stoke Institute for Science and Technology in MedicineKeele UniversityStoke-on TrentUK Department of Neurology Oslo University HospitalOsloNorway Research and Development Norwegian Air Ambulance FoundationOsloNorway Department of Neurology and Comprehensive Stroke Center David Geffen School of MedicineUCLALos AngelesCaliforniaUSA Research and Graduate Services University of NottinghamNottinghamUK Community and Health Research Unit University of LincolnLincolnUK

Background The effect of transdermal glyceryl trinitrate(GTN,a nitrovasodilator)on clinical outcome when administered before hospital admission in suspected stroke patients is ***,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 *** primary outcome was a shift in scores on the modified Rankin scale(mRS)at day *** 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’*** were reported as n(%),mean(SD),median[IQR],adjusted common OR(acOR),mean difference or mann-Whitney difference(mWD)with 95%*** 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]***‘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 *** 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 *** IS ALREADY KNOWN ON THIS TOPIC⇒Transdermal glyceryl trinitrate(GTN)was associat-ed with less death and dependency in those w

关键词： Glasgow nitrate random

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Blood pressure management in acute stroke

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Stroke & Vascular Neurology 2016年第2期1卷 72-82页

作者： Jason P Appleton Nikola Sprigg philip m bath Stroke Trials Unit Division of Clinical NeuroscienceUniversity of NottinghamNottinghamUK

Blood pressure(BP)is elevated in 75%or more of patients with acute stroke and is associated with poor *** to modulate BP in acute stroke has long been *** the loss of normal cerebral autoregulation,theoretical concerns are twofold:high BP can lead to cerebral oedema,haematoma expansion or haemorrhagic transformation;and low BP can lead to increased cerebral infarction or perihaematomal *** evidence from multiple large,high-quality,randomised trials is increasing our understanding of this challenging area,such that BP lowering is recommended in acute intracerebral haemorrhage and is safe in ischaemic *** we review the evidence for BP modulation in acute stroke,discuss the issues raised and look to on-going and future research to identify patient subgroups who are most likely to benefit.

关键词： Blood acute cerebral

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Cerebral misery perfusion due to carotid occlusive disease

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Stroke & Vascular Neurology 2017年第2期2卷 88-93页

作者： mohana maddula Nikola Sprigg philip m bath Sunil munshi Acute Stroke Unit Tauranga HospitalTaurangaNew Zealand Division of Clinical Neuroscience University of NottinghamNottinghamUK Department of Stroke Nottingham University Hospitals NHS TrustNottinghamUK

Purpose Cerebral misery perfusion(CmP)is a condition where cerebral autoregulatory capacity is exhausted,and cerebral blood supply in insufficient to meet metabolic *** present an educational review of this important condition,which has a range of clinical *** A non-systematic review of published literature was undertaken on CmP and major cerebral artery occlusive disease,using Pubmed and *** Patients with CmP may present with strokes in watershed territories,collapses and transient ischaemic attacks or episodic movements associated with an orthostatic *** positron emission tomography is the gold standard investigation for misery perfusion,advanced mRI is being increasingly used as an alternative investigation *** presence of CmP increases the risk of *** addition to the devastating effect of stroke,there is accumulating evidence of impaired cognition and quality of life with carotid occlusive disease(COD)and misery *** evidence for revascularisation in the setting of complete carotid occlusion is *** management constitutes careful blood pressure management while addressing other vascular risk *** The evidence for the management of patients with COD and CmP is discussed,together with recommendations based on our local *** this review,we focus on misery perfusion due to *** Patients with CmP and COD may present with a wide-ranging clinical phenotype and therefore to many *** identification of patients with misery perfusion may allow appropriate management and focus on strategies to maintain or improve cerebral blood flow,while avoiding potentially harmful treatment.

关键词： perfusion carotid impaired

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Remote platelet function testing using P-selectin expression in patients with recent cerebral ischaemia on clopidogrel

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Stroke & Vascular Neurology 2021年第1期6卷 103-108页

作者： Jason philip Appleton Carla Richardson Natalia Dovlatova Jane may Nikola Sprigg Stan Heptinstall philip m bath Stroke Trials Unit Division of Clinical NeuroscienceUniversity of NottinghamNottinghamUK Stroke Division Nottingham University Hospitals NHS TrustNottinghamUK Platelet Solutions Ltd Division of Clinical NeuroscienceQueen's Medical CentreUniversity of NottinghamNottinghamUK Platelet Research Group Division of Clinical NeuroscienceQueen's Medical CentreUniversity of NottinghamNottinghamUK

Background Antiplatelet agents reduce recurrence after cerebral ischaemia but are not effective in all patients,in part because of treatment *** primary aim was to assess the proportion of patients who are insensitive to *** secondary aim was to assess the association between insensitivity to clopidogrel and recurrent cerebrovascular *** Following written informed consent,independent patients with a recent non-cardioembolic ischaemic stroke or transient ischaemic attack,and taking clopidogrel,were *** function was assessed with remote measurement of surface expression of P-selectin(CD62P)using commercial kits sensitive to aspirin or ***’general practitioners provided details on recurrent vascular events at least 90 days *** are mean(SD)and median[IQR].Resistance was defined as:aspirin median fluorescence(mF)>500 units,clopidogrel mF>860 ***-parametric descriptors and tests were *** 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 *** 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 ***(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=*** Remote measurement of platelet function assessed using the platelet surface expression of P-selectin is feasible.11%of patients taking clopidogrel showed *** significant associations were noted between clopidogrel resistance and recurrent ischaemic events.

关键词： patients cerebral function

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measures of intracranial compartments in acute intracerebral haemorrhage:data from the Rapid Intervention with Glyceryl Trinitrate in Hypertensive Stroke-2 Trial(RIGHT-2)

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Stroke & Vascular Neurology 2023年第2期8卷 151-160页

作者： Kailash Krishnan Zhe Kang Law Lisa J Woodhouse Rob A Dineen Nikola Sprigg Joanna m Wardlaw philip m bath Stroke Department of Acute MedicineNottingham University Hospitals NHS TrustNottinghamUK Stroke Trials Unit University of NottinghamNottinghamUK Department of medicine National University of Malaysia Faculty of MedicineKuala LumpurMalaysia Radiological Sciences Research Group University of NottinghamNottinghamUK National Institute of Health Research Nottingham Biomedical Research Centre University of NottinghamNottinghamUK Centre for Clinical Brain Sciences UK Dementia Research InstituteChancellor's BuildingUniversity of EdinburghEdinburghUK

Background and purpose Intracerebral haemorrhage volume(ICHV)is prognostically important but does not account for intracranial volume(ICV)and cerebral parenchymal volume(CPV).We assessed measures of intracranial compartments in acute ICH using computerised tomography scans and whether ICHV/ICV and ICHV/CPV predict functional *** also assessed if cistern effacement,midline shift,old infarcts,leukoaraiosis and brain atrophy were associated with *** Data from 133 participants from the Rapid Intervention with Glyceryl Trinitrate in Hypertensive Stroke-2 Trial trial were *** included ICHV(using ABC/2)and ICV(XYZ/2)(by independent observers);ICHV,ICV and CPV(semiautomated segmentation,SAS);atrophy(intercaudate distance,ICD,Sylvian fissure ratio,SFR);midline shift;leukoaraiosis and cistern effacement(visual assessment).The effects of these measures on death at day 4 and poor functional outcome at day 90(modified Rankin scale,mRS of>3)was *** ICV was significantly different between XYZ and SAS:mean(SD)of 1357(219)vs 1420(196),mean difference(mD)62 mL(pment for ICV measured by SAS,CPV,ICD,SFR,leukoaraiosis and cistern score(all interclass correlations,n=10:interobserver 0.72-0.99,intraobserver 0.73-1.00).ICHV/ICV and ICHV/CPV were significantly associated with mRS at day 90,death at day 4 and acute neurological deterioration(all pmilar to *** shift and cistern effacement at baseline were associated with poor functional outcome but old infarcts,leukoaraiosis and brain atrophy were *** Intracranial compartment measures and visual estimates are *** adjusted for ICH and CPV could be useful to prognosticate in acute *** presence of midline shift and cistern effacement may predict outcome but the mechanisms need validation in larger studies.

关键词： measures Tri nitrate

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Cilostazol and isosorbide mononitrate for the prevention of progression of cerebral small vessel disease:baseline data and statistical analysis plan for the Lacunar Intervention Trial-2(LACI-2)(ISRCTN14911850)

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Stroke & Vascular Neurology 2023年第2期8卷 134-143页

作者： philip m bath Iris mhlanga Lisa J Woodhouse Fergus Doubal Katherine Oatey Alan A montgomery Joanna m Wardlaw LACI-Trial Investigators Stroke Trials Unit University of NottinghamNottinghamUK Centre for Clinical Brain Sciences UK Dementia Research Institute CentreUniversity of EdinburghEdinburghUK Edinburgh Clinical Trials Unit University of EdinburghEdinburghUK Nottingham Clinical Trials Unit University of NottinghamNottinghamUK

Background Cerebral small vessel disease(SVD)causes lacunar strokes(25%of all ischaemic strokes),physical frailty and cognitive impairment and vascular and mixed *** is no specific treatment to prevent progression of *** The LACunar Intervention Trial-2 is an investigator-initiated prospective randomised open-label blinded-endpoint phase II feasibility study assessing cilostazol and isosorbide mononitrate for preventing SVD *** aimed to recruit 400 patients with clinically evident lacunar ischaemic stroke and randomised to cilostazol,isosorbide mononitrate,both or neither,in addition to guideline secondary ischaemic stroke prevention,in a partial factorial *** primary outcome is feasibility of recruitment and adherence to medication;key secondary outcomes include:drug tolerability;recurrent vascular events,cognition and function at 1 year after randomisation;and safety(bleeding,falls,death).Data are number(%)and median(IQR).Results The trial commenced on 5 February 2018 and ceased recruitment on 31 may 2021 with 363 patients randomised,with the following baseline characteristics:average age 64(56.0,72.0)years,female 112(30.9%),stroke onset to randomisation 79.0(27.0,244.0)days,hypertension 267(73.6%),median blood pressures 143.0(130.0,157.0)/83.0(75.0,90.0)mm Hg,current smokers 67(18.5%),educationally achieved end of school examinations(A-level)or higher 118(32.5%),modified Rankin scale 1.0(0.0,1.0),National Institutes Health stroke scale 1.0(1.4),montreal Cognitive Assessment 26.0(23.0,28.0)and total SVD score on brain imaging 1.0(0.0,2.0).This publication summarises the baseline data and presents the statistical analysis *** The trial is currently in follow-up which will complete on 31 may 2022 with results expected in October *** registration number ISRCTN14911850.

关键词： nitrate initiated prevention

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Clopidogrel with aspirin in High- risk patients with Acute Non- disabling Cerebrovascular Events II (CHANCE-2): rationale and design of a multicentre randomised trial

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Stroke & Vascular Neurology 2021年第2期6卷 280-285页

作者： Yongjun Wang Claiborne Johnston philip m bath Xia meng Jing Jing Xuewei Xie Anxin Wang Yuesong Pan Anding Xu Qiang Dong Yilong Wang Xingquan Zhao Zixiao Li Hao Li Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina China National Clinical Research Center for Neurological Diseases BeijingChina The University of Texas at Austin Dell medical School AustinTexasUSA Stroke Trials Unit Division of Clinical NeuroscienceUniversity of NottinghamNottinghamUK Department of Neurology The First Affiliated HospitalJinan University GuangzhouGuangzhouGuangdongChina Department of Neurology Huashan HospitalState Key Laboratory of Medical NeurobiologyFudan UniversityShanghaiChina

Background In patients with a minor ischaemic stroke or transient ischaemic attack(TIA),separate trials have shown that dual antiplatelet therapy with clopidogrel plus aspirin(clopidogrel-aspirin)or ticagrelor plus aspirin(ticagrelor-aspirin)are more effective than aspirin alone in stroke secondary ***,these two sets of combination have not been directly *** clopidogrel was less effective in stroke patients who were CYP2C19 loss-of function(LOF)allele carriers,whether ticagrelor-aspirin is clinically superior to clopidogrel-aspirin in this subgroup of patients with stroke is *** To describe the rationale and design considerations of the Clopidogrel in High-risk patients with Acute Non-disabling Cerebrovascular Events(CHANCE-2)*** CHANCE-2 is a randomised,double-blind,double-dummy,placebo-controlled,multicentre trial that compares two dual antiplatelet strategies for minor stroke or TIA patients who are CYP2C19 LOF allele carriers:ticagrelor(180 mg loading dose on day 1 followed by 90 mg twice daily on days 2-90)or clopidogrel(300 mg loading dose on day 1 followed by 75 mg daily on days 2-90),plus open-label aspirin with a dose of 75-300 mg on day 1 followed by 75 mg daily on day *** will be followed for 1 *** outcomes The primary efficacy outcome is any stroke(ischaemic or haemorrhagic)within 3 months and the primary safety outcome is any severe or moderate bleeding event within 3 *** The CHANCE-2 trial will evaluate whether ticagrelor-aspirin is superior to clopidogrel-aspirin for minor stroke or TIA patients who are CYP2C19 LOF allele carriers.

关键词： CYP2C19 aspirin patients

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Relationship between nitrate headache and outcome in patients with acute stroke: results from the efficacy of nitric oxide in stroke (ENOS) trial

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Stroke & Vascular Neurology 2021年第2期6卷 180-186页

作者： Lucy Beishon Lisa J Woodhouse Daniel Bereczki Hanne K Christensen Ronan Collins John Gommans Christina Kruuse George Ntaios Serefnur Ozturk Stephen Phillips Stuart Pocock Szabolcs Szatmari Joanna Wardlaw Nikola Sprigg philip m bath Stroke Trials Unit Division of Clinical NeuroscienceUniversity of NottinghamNottinghamUK Department of Neurology Semmelweis UniversityBudapestHungary Bispebjerg Hospital and University of Copenhagen University of CopenhagenCopenhagenDenmark Department of Geriatric and Stroke medicine Adelaide and Meath HospitalDublinIreland Department of medicine Hawke's Bay HospitalCamberleyNew Zealand Department of Neurology Herlev Gentofte HospitalUniversity of CopenhagenCopenhagenDenmark Department of medicine Larissa University HospitalUniversity of ThessalyVolosGreece Department of Neurology Selcuk University Medical FacultyKonyaTurkey Department of Neurology Queen Elizabeth II Health Sciences CentreHalifaxNova ScotiaCanada medical Statistics Unit London School of Hygiene&Tropical MedicineLondonUK Department of Neurology George Emil Palade University of MedicinePharmacyScience and Technology of Târgu MureșTargu MuresRomania Centre for Clinical Brain Sciences University of EdinburghEdinburghUK Stroke Nottingham University Hospitals NHS TrustNottinghamUK

Introduction Nitrate-induced headache is common and may signify responsive cerebral *** assessed the relationship between nitrate headache and outcome in patients with acute *** and methods Patients were those randomised to glyceryl trinitrate(GTN)versus no GTN in the efficacy of nitric oxide in stroke *** of headache by end of treatment(day 7),and functional outcome(modified Rankin Scale,primary outcome)at day 90,were *** are adjusted for baseline prognostic factors and give OR and mean difference(mD)with 95%*** In 4011 patients,headache was more common in GTN than control(360,18.0% vs 170,8.5%;pmale sex,higher diastolic blood pressure,non-total anterior circulation syndrome,milder stroke and absence of dysphasia(pmproved functional outcome(OR 0.90,95% CI 0.73 to 1.10,p=0.30)or death(day 90)(HR 0.64,95% CI 0.40 to 1.02,p=0.062),but reduced death or deterioration(day 7)(OR 0.45,95% CI 0.25 to 0.82),death in hospital(OR 0.44,95% CI 0.22 to 0.88)and improved activities of daily living(Barthel index,mD 3.7,95% CI 0.3 to 7.1)and cognition(telephone interview cognitive screen,mD 2.0,95% CI 0.7 to 3.3)(day 90).Non-nitrate headache was not associated with death,disability or *** and conclusion Development of a nitrate headache by day 7 after stroke may be associated with improved activities of daily living and cognitive impairment at day 90,which was not seen with non-nitrate headache.

关键词： headache patients nitrate

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Clinical management of cerebral small vessel disease:a call for a holistic approach

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Chinese medical Journal 2021年第2期134卷 127-142页

作者： Una Clancy Jason P.Appleton Carmen Arteaga Fergus N.Doubal philip m.bath Joanna m.Wardlaw Centre for Clinical Brain Sciences and UK Dementia Research InstituteUniversity of EdinburghChancellor's Building49 Little France CrescentEdinburghEH164SPUK Stroke Trials Unit Division of Clinical NeuroscienceUniversity of NottinghamNottingham NG51PBUK Stroke University Hospitals Birmingham NHS Foundation TrustMindelsohn WayEdgbastonBirmingham B152GWUK Stroke Nottingham University Hospitals NHS TrustNottingham NG51PBUK.

Cerebral small vessel disease(SVD)is a common global brain disease that causes cognitive impairment,ischemic or hemorrhagic stroke,problems with mobility,and neuropsychiatric *** brain damage,seen as focal white and deep grey matter lesions on brain magnetic resonance imaging(mRI)or computed tomography(CT),typically accumulates"covertly"and may reach an advanced state before being detected incidentally on brain scanning or causing *** have typically presented to different clinical services or been recruited into research focused on one clinical manifestation,perhaps explaining a lack of awareness,until recently,of the full range and complexity of *** this review,we discuss the varied clinical presentations,established and emerging risk factors,relationship to SVD features on mRI or CT,and the current state of knowledge on the effectiveness of a wide range of pharmacological and lifestyle *** core message is that effective assessment and clinical management of patients with SVD,as well as future advances in diagnosis,care,and treatment,will require a more"joined-up"’*** approach should integrate clinical expertise in stroke neurology,cognitive,and physical *** requires more clinical trials in order to improve pharmacological interventions,lifestyle and dietary modifications.A deeper understanding of the pathophysiology of SVD is required to steer the identification of novel *** essential prerequisite to accelerating clinical trials is to improve the consistency,and standardization of clinical,cognitive and neuroimaging endpoints.

关键词： Dementia magnetic resonance imaging mild cognitive impairment Risk factors Small vessel disease Stroke Symptoms Treatment

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Rationale and design of a randomised double-blind 2×2 factorial trial comparing the effect of a 3-month intensive statin and antiplatelet therapy for patients with acute mild ischaemic stroke or high-risk TIA with intracranial or extracranial atherosclerosis(INSPIRES)

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Stroke & Vascular Neurology 2023年第3期8卷 249-258,I0096-I0110页

作者： Ying Gao Yuesong Pan Shangrong Han Weiqi Chen Jing Jing Chunjuan Wang Yingying Yang Tingting Wang Xia meng Xingquan Zhao Liping Liu Hao Li S Claiborne Johnston Pierre Amarenco philip m bath Yongjun Wang Yilong Wang Department of Neurology Beijing Tiantan HospitalCapital Medical UniversityBeijingChina China National Clinical Research Center for Neurological Diseases Beijing Tiantan HospitalCapital Medical UniversityBeijingChina Dean's Office Dell Medical SchoolUniversity of Texas at AustinAustinTexasUSA Department of Neurology and Stroke Center Assistance Publique-Hôpitaux de Paris(APHP)Bichat HospitalINSERM LVTS-U1148University of ParisParisFrance Population Health Research Institute McMaster UniversityHamiltonOntarioCanada Stroke Trials Unit Mental Health&Clinical NeuroscienceUniversity of NottinghamNottinghamUK Advanced Innovation Center for Human Brain Protection Capital Medical UniversityBeijingChina National Center for Neurological Diseases BeijingChina Research Unit of Artificial Intelligence in Cerebrovascular Disease Chinese Academy of Medical SciencesBeijingChina Chinese Institute for Brain Research BeijingChina

Background It remains unclear if intensive antiplatelet and statin treatments begun within 24-72 hours of cerebral ischaemic events from intracranial or extracranial atherosclerosis is effective or *** The Intensive Statin and Antiplatelet Therapy for High-risk Intracranial or Extracranial Atherosclerosis(INSPIRES)trial is a randomised,double-blind,placebo-controlled,multicentre and 2×2 factorial trial.6100 individuals between the ages of 35 and 80 who have experienced a mild ischaemic stroke or high-risk transient ischaemic attack(TIA)within the previous 72 hours that is attributed to≥50%atherosclerotic stenosis of a major intracranial or extracranial artery or multiple infarctions of atherosclerotic origin will be enrolled in the *** subjects will be randomised 1:1:1:1 to one of four groups:(1)intensive antiplatelet therapy(combined clopidogrel and aspirin for days 1-21,then aspirin placebo and clopidogrel for days 22-90)plus immediate intensive statin therapy(atorvastatin at a dose of 80 mg daily for the first 21 days,then 40 mg daily for days 22-90);(2)intensive antiplatelet therapy plus delayed intensive statin therapy(atorvastatin placebo for days 1-3,followed by 40 mg per day of atorvastatin for days 4-90);(3)standard antiplatelet therapy(combination of clopidogrel placebo with aspirin for 90 days)plus immediate intensive statin therapy and(4)standard antiplatelet therapy plus delayed intensive statin *** primary efficacy endpoint is any new stroke(ischaemic or haemorrhagic)within 90 days after *** primary safety endpoint is moderate to severe bleeding at 90 *** The INSPIRES trial will assess the efficacy and safety of intensive antiplatelet therapy and immediate intensive statin therapy begun within 72 hours of onset in decreasing the recurrent stroke at 90 days in patients with acute mild ischaemic stroke or high-risk TIA of intracranial or extracranial atherosclerosis origin.

关键词： intracranial atherosclerosis random

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