Pioglitazone for secondary prevention after ischemic stroke and transient ischemic attack: rationale and design of the Insulin Resistance Intervention after Stroke Trial. Peer education for secondary stroke prevention in inner-city minorities: design and methods of the prevent recurrence of all inner-city strokes through education randomized controlled trial. VITATOPS, the VITAmins TO Prevent Stroke Trial: Rationale and Design of a Randomised Trial of B-Vitamin Therapy in Patients with Recent Transient Ischaemic Attack or Stroke (NCT00097669) (ISRCTN74743444) Secondary prevention in non-rheumatic atrial fibrillation after transient ischaemic attack or minor stroke Reductions in the risks of recurrent stroke in patients with and without diabetes: The PROGRESS Trial The Adherence eValuation After Ischemic Stroke Longitudinal (AVAIL) registry: design, rationale, and baseline patient characteristics. Mixed methods feasibility study for a trial of blood pressure telemonitoring for people who have had stroke/transient ischaemic attack (TIA) Terutroban versus aspirin in patients with cerebral ischaemic events (PERFORM): a randomised, double-blind, parallel-group trial Intensified secondary prevention intending a reduction of recurrent events in TIA and minor stroke patients (INSPiRE-TMS): a protocol for a randomised controlled trial The Secondary Prevention of Small Subcortical Strokes (SPS3) Study Program of rehabilitative exercise and education to avert vascular events after non-disabling stroke or transient ischemic attack (PREVENT Trial): a multi-centred, randomised controlled trial Combining Multiple Approaches for the Secondary Prevention of Vascular Events After Stroke: A Quantitative Modeling Study Population based study of early risk of stroke after transient ischaemic attack or minor stroke: implications for public education and organisation of services Update to the AHA/ASA recommendations for the prevention of stroke in patients with stroke and transient ischemic attack. Rivaroxaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: a subgroup analysis of ROCKET AF A Randomised Controlled Trial of Triple Antiplatelet Therapy (Aspirin, Clopidogrel and Dipyridamole) in the Secondary Prevention of Stroke: Safety, Tolerability and Feasibility Effects of Pioglitazone for Secondary Stroke Prevention in Patients with Impaired Glucose Tolerance and Newly Diagnosed Diabetes: The J-SPIRIT Study. Effect of urgent treatment of transient ischaemic attack and minor stroke on early recurrent stroke (EXPRESS study): a prospective population-based sequential comparison The preventing recurrent vascular events and neurological worsening through intensive organized case-management (PREVENTION) trial protocol [clinicaltrials.gov identifier: NCT00931788] Effect of urgent treatment for transient ischaemic attack and minor stroke on disability and hospital costs (EXPRESS study): a prospective population-based sequential comparison Long-term risk of first recurrent stroke in the Perth Community Stroke Study. B vitamins in patients with recent transient ischaemic attack or stroke in the VITAmins TO Prevent Stroke (VITATOPS) trial: a randomised, double-blind, parallel, placebo-controlled trial Trial of Secondary Prevention With Atenolol After Transient Ischemic Attack or Nondisabling Ischemic Stroke
BACKGROUND Recurrent vascular events remain a major source of morbidity and mortality after stroke or transient ischemic attack ( TIA ) . The IRIS Trial is evaluating an approach to secondary prevention based on the established association between insulin resistance and increased risk for ischemic vascular events . Specifically , IRIS will test the effectiveness of pioglitazone , an insulin-sensitizing drug of the thiazolidinedione class , for reducing the risk for stroke and myocardial infa rct ion ( MI ) among insulin resistant , nondiabetic patients with a recent ischemic stroke or TIA . DESIGN Eligible patients for IRIS must have had insulin resistance defined by a Homeostasis Model Assessment -Insulin Resistance > 3.0 without meeting criteria for diabetes . Within 6 months of the index stroke or TIA , patients were r and omly assigned to pioglitazone ( titrated from 15 to 45 mg/d ) or matching placebo and followed for up to 5 years . The primary outcome is time to stroke or MI . Secondary outcomes include time to stroke alone , acute coronary syndrome , diabetes , cognitive decline , and all-cause mortality .  Enrollment of 3,876 participants from 179 sites in 7 countries was completed in January 2013 . Participant follow-up will continue until July 2015 . SUMMARY The IRIS Trial will determine whether treatment with pioglitazone improves cardiovascular outcomes of nondiabetic , insulin-resistant patients with stroke or TIA . Results are expected in early 2016 BACKGROUND The highest risk for stroke is among survivors of strokes or transient ischemic attacks ( TIA ) . However , use of proven-effective cardiovascular medications to control stroke risk is suboptimal , particularly among the Black and Latino population s disproportionately impacted by stroke . METHODS A partnership of Harlem and Bronx community representatives , stroke survivors , research ers , clinicians , outreach workers and patient educators used community-based participatory research to conceive and develop the Prevent Recurrence of All Inner-city Strokes through Education ( PRAISE ) trial . Using data from focus groups with stroke survivors , they tailored a peer-led , community-based chronic disease self-management program to address stroke risk factors . PRAISE will test , in a r and omized controlled trial , whether this stroke education intervention improves blood pressure control and a composite outcome of blood pressure control , lipid control , and use of antithrombotic medications . RESULTS Of the 582 survivors of stroke and TIA enrolled thus far , 81 % are Black or Latino and 56 % have an annual income less than $ 15,000 . Many ( 33 % ) do not have blood pressures in the target range , and most ( 66 % ) do not have control of all three major stroke risk factors . CONCLUSIONS Rates of stroke recurrence risk factors remain suboptimal in the high risk , urban , predominantly minority communities studied . With a community-partnered approach , PRAISE has recruited a large number of stroke and TIA survivors to date , and may prove successful in engaging those at highest risk for stroke and reducing disparities in stroke outcomes in inner-city communities Background Epidemiological studies suggest that raised plasma concentrations of total homocysteine ( tHcy ) may be a common , causal and treatable risk factor for atherothromboembolic ischaemic stroke , dementia and depression . Although tHcy can be lowered effectively with small doses of folic acid , vitamin B12 and vitamin B6 , it is not known whether lowering tHcy , by means of B vitamin therapy , can prevent stroke and other major atherothromboembolic vascular events . Aim To determine whether the addition of B-vitamin supplements ( folic acid 2 mg , B6 25 mg , B12 500 μg ) to best medical and surgical management will reduce the combined incidence of stroke , myocardial infa rct ion ( MI ) and vascular death in patients with recent stroke or transient ischaemic attack ( TIA ) of the brain or eye . Design A prospect i ve , international , multicentre , r and omised , double blind , placebo-controlled clinical trial . Setting One hundred and four medical centres in 20 countries on five continents . Subjects Eight thous and ( 6600 recruited as of 5 January , 2006 ) patients with recent ( 7 months ) stroke ( ischaemic or haemorrhagic ) or TIA ( brain or eye ) . R and omisation R and omisation and data collection are performed by means of a central telephone service or secure internet site . Intervention One tablet daily of either placebo or B vitamins ( folic acid 2 mg , B6 25 mg , B12 500 μg ) . Primary outcome The composite of stroke , MI or death from any vascular cause , whichever occurs first . Outcome and serious adverse events are adjudicated blinded to treatment allocation . Secondary outcomes TIA , unstable angina , revascularisation procedures , dementia , depression . Statistical power With 8000 patients followed up for a median of 2 years and an annual incidence of the primary outcome of 8 % among patients assigned placebo , the study will have at least 80 % power to detect a relative reduction of 15 % in the incidence of the primary outcome among patients assigned B vitamins ( to 6·8%/year ) , applying a two-tailed level of significance of 5 % . Conclusion VITATOPS aims to recruit and follow-up 8000 patients between 1998 and 2008 , and provide a reliable estimate of the safety and effectiveness of folic acid , vitamin B12 , and vitamin B6 supplementation in reducing recurrent serious vascular events among a wide range of patients with TIA and stroke throughout the world Several studies have established the value of anticoagulation for primary prevention of thromboembolic events in patients with non-rheumatic atrial fibrillation ( NRAF ) . However , in patients with a recent transient ischaemic attack ( TIA ) or minor ischaemic stroke the preventive benefit of anticoagulation or aspirin remains unclear . Physicians in 108 centres from 13 countries collaborated to study this question . 1007 NRAF patients with a recent TIA or minor ischaemic stroke were r and omised to open anticoagulation or double-blind treatment with either 300 mg aspirin per day or placebo ( group 1 , 669 ) . Patients with contraindications to anticoagulation were r and omised to receive aspirin or placebo ( group 2,338 ) . The measure of outcome was death from vascular disease , any stroke , myocardial infa rct ion , or systemic embolism . During mean follow-up of 2.3 years , the annual rate of outcome events was 8 % in patients assigned to anticoagulants vs 17 % in placebo-treated patients in group 1 ( hazard ratio [ HR ] 0.53 ; 95 % confidence interval [ CI ] 0.36 - 0.79 ) . The risk of stroke alone was reduced from 12 % to 4 % per year ( HR 0.34 ; 95 % CI 0.20 - 0.57 ) . Among all patients assigned to aspirin ( groups 1 and 2 ) , the annual incidence of outcome events was 15 % , against 19 % in those on placebo ( HR 0.83 ; 95 % CI 0.65 - 1.05 ) . Anticoagulation was significantly more effective than aspirin ( HR 0.60 ; 95 % CI 0.41 - 0.87 ) . The incidence of major bleeding events was low , both on anticoagulation ( 2.8 % per year ) and on aspirin ( 0.9 % per year ) . No intracranial bleeds were identified in patients assigned to anticoagulation . We conclude that anticoagulation is effective in reducing the risk of recurrent vascular events in NRAF patients with a recent TIA or minor ischaemic stroke . In absolute terms : 90 vascular events ( mainly strokes ) are prevented if 1000 patients are treated with anticoagulation for one year . Aspirin is a safe , though less effective , alternative when anticoagulation is contraindicated ; it prevents 40 vascular events each year for every 1000 treated patients Background : Analyses of the risks of stroke were conducted for subjects with and without diabetes , participating in a r and omized , double‐blind , placebo‐controlled  trial of a perindopril‐based blood pressure lowering regimen in 6105 people with prior stroke or transient ischaemic attack ( TIA ) , followed for a median of 3.9 years . Findings : Seven hundred and sixty‐one patients had diabetes at baseline . Diabetes increased the risk of recurrent stroke by 35 % ( 95 % CI 10–65 % ) principally through an effect on ischaemic stroke ( 1.53 , 95 % CI 1.23–1.90 ) . Active treatment reduced blood pressure by 9.5/4.6 mmHg in patients with diabetes and by 8.9/3.9 mmHg in patients without diabetes . The proportional risk reductions achieved for stroke in patients with diabetes , 38 % ( 95 % CI 8–58 % ) , and patients without diabetes , 28 % ( 95 % CI 16–39 % ) , were not significantly different ( p homogeneity = 0.5 ) . The absolute reduction in the risk of recurrent stroke in the patients with diabetes was equivalent to one stroke avoided among every 16 ( 95 % CI 9–111 ) patients treated for 5 years . Conclusions : Diabetes is an important risk factor for stroke in patients with established cerebrovascular disease . Treatment with the ACE inhibitor perindopril with discretionary use of the diuretic indapamide produced reductions in the risk of recurrent stroke in patients with diabetes that were at least as great as those achieved in patients without diabetes BACKGROUND Approximately one third of the 780,000 people in the United States who have a stroke each year have recurrent events . Although efficacious secondary prevention measures are available , levels of adherence to these strategies in patients who have had stroke are largely unknown . Underst and ing medication-taking behavior in this population is an important step to optimizing the appropriate use of proven secondary preventive therapies and reducing the risk of recurrent stroke . METHODS The Adherence eValuation After Ischemic Stroke Longitudinal ( AVAIL ) registry is a prospect i ve study of adherence to stroke prevention medications from hospital discharge to 1 year in patients admitted with stroke or transient ischemic attack . The primary outcomes are medication usage as determined by patient interviews after 3 and 12 months . Potential patient- , provider- , and system-level barriers to persistence of medication use are also collected . Secondary outcomes include the rates of recurrent stroke or transient ischemic attack , vascular events , and rehospitalization and functional status as measured by the modified Rankin score . RESULTS The AVAIL enrolled about 2,900 subjects from 106 hospitals from July 2006 through July 2008 . The 12-month follow-up will be completed in August 2009 . CONCLUSIONS The AVAIL registry will document the current state of adherence and persistence to stroke prevention medications among a nationwide sample of patients . These data will be used to design interventions to improve the quality of care post acute hospitalization and reduce the risks of future stroke and cardiovascular events Background Good blood pressure ( BP ) control reduces the risk of recurrence of stroke/transient ischaemic attack ( TIA ) . Although there is strong evidence that BP telemonitoring helps achieve good control , none of the major trials have considered the effectiveness in stroke/TIA survivors . We therefore conducted a feasibility study for a trial of BP telemonitoring for stroke/TIA survivors with uncontrolled BP in primary care . Method Phase 1 was a pilot trial involving 55 patients stratified by stroke/TIA r and omised 3:1 to BP telemonitoring for 6 months or usual care . Phase 2 was a qualitative evaluation and comprised semi-structured interviews with 16 trial participants who received telemonitoring and 3 focus groups with 23 members of stroke support groups and 7 carers . Results Overall , 125 patients ( 60 stroke patients , 65 TIA patients ) were approached and 55 ( 44 % ) patients were r and omised including 27 stroke patients and 28 TIA patients . Fifty-two participants ( 95 % ) attended the 6-month follow-up appointment , but one declined the second daytime ambulatory blood pressure monitoring ( ABPM ) measurement result ing in a 93 % completion rate for ABPM − the proposed primary outcome measure for a full trial . Adherence to  telemonitoring  was good ; of the 40 participants who were  telemonitoring  , 38 continued to provide readings throughout the 6 months . There was a mean reduction of 10.1 mmHg in systolic ABPM in the telemonitoring group compared with 3.8 mmHg in the control group , which suggested the potential for a substantial effect from telemonitoring . Our qualitative analysis found that many stroke patients were concerned about their BP and telemonitoring increased their engagement , was easy , convenient and reassuring . Conclusions A full-scale trial is feasible , likely to recruit well and have good rates of compliance and follow-up . Trial Registration IS RCT N61528726 15/12/2011 BACKGROUND Patients with ischaemic stroke or transient ischaemic attack ( TIA ) are at high risk of recurrent stroke or other cardiovascular events . We compared the selective thromboxane-prostagl and in receptor antagonist terutroban with aspirin in the prevention of cerebral and cardiovascular ischaemic events in patients with a recent non-cardioembolic cerebral ischaemic event . METHODS This r and omised , double-blind , parallel-group trial was undertaken in 802 centres in 46 countries . Patients who had an ischaemic stroke in the previous 3 months or a TIA in the previous 8 days were r and omly allocated with a central interactive response system to 30 mg per day terutroban or 100 mg per day aspirin . Patients and investigators were masked to treatment allocation . The primary efficacy endpoint was a composite of fatal or non-fatal ischaemic stroke , fatal or non-fatal myocardial infa rct ion , or other vascular death ( excluding haemorrhagic death ) . We planned a sequential statistical analysis of non-inferiority ( margin 1·05 ) followed by analysis of superiority . Analysis was by intention to treat . The study was stopped prematurely for futility on the basis of the recommendation of the Data Monitoring Committee . This study is registered , number IS RCT N66157730 . FINDINGS 9562 patients were assigned to terutroban ( 9556 analysed ) and 9558 to aspirin ( 9544 analysed ) ; mean follow-up was 28·3 months ( SD 7·7 ) . The primary endpoint occurred in 1091 ( 11 % ) patients receiving terutroban and 1062 ( 11 % ) receiving aspirin ( hazard ratio [ HR ] 1·02 , 95 % CI 0·94 - 1·12 ) . There was no evidence of a difference between terutroban and aspirin for the secondary or tertiary endpoints . We recorded some increase in minor bleedings  with terutroban compared with aspirin ( 1147 [ 12 % ] vs 1045 [ 11 % ] ; HR 1·11 , 95 % CI 1·02 - 1·21 ) , but no significant differences in other safety endpoints . INTERPRETATION The trial did not meet the predefined criteria for non-inferiority , but showed similar rates of the primary endpoint with terutroban and aspirin , without safety advantages for terutroban . In a worldwide perspective , aspirin remains the gold st and ard antiplatelet drug for secondary stroke prevention in view of its efficacy , tolerance , and cost . FUNDING Servier , France Background Patients with recent stroke or TIA are at high risk for new vascular events . Several evidence based strategies in secondary prevention of stroke are available but frequently underused . Support programs with multifactorial risk factor modifications after stroke or TIA have not been investigated in large-scale prospect i ve controlled trials so far . INSPiRE-TMS is a prospect i ve , multi-center , r and omized open intervention trial for intensified secondary prevention after minor stroke and TIA . Methods / design Patients with acute TIA or minor stroke admitted to the participating stroke centers are screened and recruited during in-hospital stay . Patients are r and omised in a 1:1 ratio to intervention ( support program ) and control ( usual care ) arms . Inclusion of 2.082 patients is planned . The support program includes cardiovascular risk factor measurement and feedback , monitoring of medication adherence , coaching in lifestyle modifications , and active involvement of relatives . St and ardized motivational interviewing is used to assess and enhance patients ’ motivation . Primary objective is a reduction of new major vascular events defined as nonfatal stroke and myocardial infa rct ion or vascular death . Recruitment time is planned for 3.5 years , follow up time is at least 2 years for every patient result ing in a total study time of 5 years ( first patient in to last patient out ) . Discussion Given the high risk for vascular re-events in acute stroke and the available effective strategies in secondary prevention , the INSPIRE-TMS support program has the potential to lead to a relevant reduction of recurrent events and a prolongation of the event-free survival time . The trial will provide the basis for the decision whether an intensified secondary prevention program after stroke should be implemented into regular care . A cost-effectiveness evaluation will be performed . Trial registration clinical trials.gov : Background Small subcortical strokes , also known as lacunar strokes , comprise more than 25 % of brain infa rcts , and the underlying vasculopathy is the most common cause of vascular cognitive impairment . How to optimally prevent stroke recurrence and cognitive decline in S3 patients is unclear . The aim of the Secondary Prevention of Small Subcortical Strokes study ( Trial registration : NCT00059306 ) is to define strategies for reducing stroke recurrence , cognitive decline , and major vascular events . Methods Secondary Prevention of Small Subcortical Strokes is a r and omised , multicentre clinical trial ( n=3000 ) being conducted in seven countries , and sponsored by the US NINDS/NIH . Patients with symptomatic small subcortical strokes in the six-months before and an eligible lesion on magnetic resonance imaging are simultaneously r and omised , in a 2 × 2 factorial design , to antiplatelet therapy – 325 mg aspirin daily plus 75 mg clopidogrel daily , vs. 325 mg aspirin daily plus placebo , double-blind – and to one of two levels of systolic blood pressure targets –‘intensive ’ ( < 130 mmHg ) vs. ‘ usual ’ ( 130–149 mmHg ) . Participants are followed for an average of four-years . Time to recurrent stroke ( ischaemic or haemorrhagic ) is the primary outcome and will be analysed separately for each intervention . The secondary outcomes are the rate of cognitive decline and major vascular events . The primary and most secondary outcomes are adjudicated central ly by those unaware of treatment assignment . Conclusions Secondary Prevention of Small Subcortical Strokes will address several important clinical and scientific questions by testing two interventions in patients with recent magnetic resonance imaging-defined lacunar infa rcts , which are likely due to small vessel disease . The results will inform the management of millions of patients with this common vascular disorder Background Despite lack of outward signs , most individuals after non-disabling stroke ( NDS ) and transient ischemic attack ( TIA ) have significant cardiovascular and cerebrovascular disease and are at high risk of a major stroke , hospitalization for other vascular events , or death . Most have multiple modifiable risk factors ( e.g. , hypertension , physical inactivity , hyperlipidaemia , diabetes , tobacco consumption , psychological stress ) . In addition , accelerated rates of depression , cognitive decline , and poor quality of sleep have been reported following TIA , which correlate with poor functional outcomes and reduced quality of life . Thus , NSD and TIA are important warning signs that should not be overlooked . The challenge is not unlike that facing other ' silent ' conditions - to identify a model of care that is effective in changing people 's current behaviors in order to avert further morbidity . Methods / Design A single blind , r and omized controlled trial will be conducted at two sites to compare the effectiveness of a program of rehabilitative exercise and education versus usual care in modifying vascular risk factors in adults after NDS/TIA . 250 adults within 90 days of being diagnosed with NDS/TIA will be r and omly allocated to a 12-week program of exercise and education ( PREVENT ) or to an outpatient clinic assessment and discussion of secondary prevention recommendations with return clinic visits as indicated ( USUAL CARE ) . Primary outcome measures will include blood pressure , waist circumference , 12-hour fasting lipid profile , and 12-hour fasting glucose/hemoglobin A1c . Secondary measures will include exercise capacity , walking endurance , physical activity , cognitive function , depression , goal attainment and health-related quality of life . Outcome assessment will be conducted at baseline , post-intervention , and 6- and 12-month follow-ups . Direct health care costs incurred over one year by PREVENT versus USUAL CARE participants will also be compared . Ethical approval for the trial has been obtained from the relevant Human Research Ethics Boards . Discussion Whether timely delivery of an adapted cardiac rehabilitation model is effective in attaining and maintaining vascular risk reduction targets in adults after NDS/TIA is not yet known . We anticipate that the findings of this trial will make a meaningful contribution to the knowledge base regarding secondary stroke prevention . Trial registration This trial is registered with the Clinical Trials.gov Registry ( NCT00885456 ) Background and Purpose — Numerous effective strategies for the secondary prevention of cardiovascular events in high-risk patients have now been established . We sought to calculate the cumulative benefit of combining multiple strategies for preventing recurrent events in patients with a history of ischemic stroke or transient ischemic attack . Methods — A comprehensive literature search was undertaken to identify meta-analyses of r and omized controlled trials reporting on the efficacy of secondary prevention strategies . The baseline incidence of vascular events was modeled from the Life Long After Cerebral Ischemia study . Strategies were combined on a multiplicative scale and cumulative risk reductions were computed over a 5-year interval . Results — The combination of 5 proven strategies applied to survivors of an initial stroke or transient ischemic attack — dietary modification , exercise , aspirin , a statin , and an antihypertensive agent — could result in a cumulative relative risk reduction of 80 % . Given a 5-year major cardiovascular event rate of 24 % , this translates to a number needed to treat of about 5 . Further gains would result from applying multimodality therapy over longer intervals and enriching the base strategy with dual antiplatelet therapy , high-dose statins , and more intensive blood pressure – lowering . Even more benefit would be present in high-risk subgroups with the addition , where appropriate , of carotid endarterectomy , moderate intensity oral anticoagulants , glycemic control , and smoking cessation . Conclusions — At least four-fifths of recurrent vascular events in patients with cerebrovascular disease might be prevented by application of a comprehensive , multifactorial approach Abstract Objective To estimate the very early stroke risk after a transient ischaemic attack ( TIA ) or minor stroke and thereby inform the planning of effective stroke prevention services . Design Population based prospect i ve cohort study of patients with TIA or stroke . Setting Nine general practice s in Oxfordshire , Engl and , from April 2002 to April 2003 . Participants All patients who had a TIA ( n = 87 ) or minor stroke ( n = 87 ) during the study period and who presented to medical attention . Main outcome measures Risk of recurrent stroke at seven days , one month , and three months after TIAs and minor strokes . Results The estimated risk of recurrent stroke was 8.0 % ( 95 % confidence interval 2.3 % to 13.7 % ) at seven days , 11.5 % ( 4.8 % to 18.2 % ) at one month , and 17.3 % ( 9.3 % to 25.3 % ) at three months after a TIA . The risks at these three time periods after a minor stroke were 11.5 % ( 4.8 % to 11.2 % ) , 15.0 % ( 7.5 % to 22.5 % ) , and 18.5 % ( 10.3 % to 26.7 % ) . Conclusions The early risks of stroke after a TIA or minor stroke are much higher than commonly quoted . More research is needed to determine whether these risks can be reduced by more rapid instigation of preventive treatment The American Heart Association/American Stroke Association ( AHA/ASA ) Writing Committee for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack ( TIA ) has review ed the results of recent trials that were published after our previous recommendations were issued.1 Our intention in the present statement is to provide a brief review of the new data , to up date specific recommendations , and to provide the reasons for any modifications . The 2 areas in which major new clinical trials have been published are ( 1 ) the use of specific antiplatelet agents for stroke prevention in patients with a history of noncardioembolic ischemic stroke or TIA and ( 2 ) the use of statins in the prevention of recurrent stroke . Recently published trials have added to the evidence of the benefit of the use of specific antiplatelet agents for stroke prevention in patients with a history of noncardioembolic ischemic stroke or TIA . The secondary prevention guidelines 1 have been up date d to reflect this new evidence . # # # Addition of Clopidogrel to Aspirin for Prevention of Vascular Events The Clopidogrel and Aspirin Versus Aspirin Alone for the Prevention of Atherothrombotic Events ( CHARISMA ) trial2 was a double-blinded study that r and omized 15 603 subjects with cardiovascular disease or multiple risk factors for cardiovascular disease to either clopidogrel 75 mg plus low-dose aspirin ( 75 to 162 mg ) or placebo plus aspirin ( 75 to 162 mg ) . Roughly 35 % of subjects ( n=4320 ) qualified on the basis of the presence of cerebrovascular disease within 5 years of enrollment ; approximately a third experienced TIA . The median follow-up was 28 months . No significant differences were seen in the rates of nonfatal ischemic stroke between the 2 groups ( 1.7 % versus 2.1 % , P = 0.07 ) . The placebo plus aspirin group showed a higher rate of nonfatal stroke than did the clopidogrel group ( 1.9 % versus 2.4 % , P = 0.03 ) . The 2 groups experienced no differences in the rate of intracerebral hemorrhage BACKGROUND In ROCKET AF , rivaroxaban was non-inferior to adjusted-dose warfarin in preventing stroke or systemic embolism among patients with atrial fibrillation ( AF ) . We aim ed to investigate whether the efficacy and safety of rivaroxaban compared with warfarin is consistent among the subgroups of patients with and without previous stroke or transient ischaemic attack ( TIA ) . METHODS In ROCKET AF , patients with AF who were at increased risk of stroke were r and omly assigned ( 1:1 ) in a double-blind manner to rivaroxaban 20 mg daily or adjusted dose warfarin ( international normalised ratio 2·0 - 3·0 ) . Patients and investigators were masked to treatment allocation . Between Dec 18 , 2006 , and June 17 , 2009 , 14 264 patients from 1178 centres in 45 countries were r and omly assigned . The primary endpoint was the composite of stroke or non-CNS systemic embolism . In this sub study we assessed the interaction of the treatment effects of rivaroxaban and warfarin among patients with and without previous stroke or TIA . Efficacy analyses were by intention to treat and safety analyses were done in the on-treatment population . ROCKET AF is registered with Clinical Trials.gov , number NCT00403767 . FINDINGS 7468 ( 52 % ) patients had a previous stroke ( n=4907 ) or TIA ( n=2561 ) and 6796 ( 48 % ) had no previous stroke or TIA .  The number of events per 100 person-years for the primary endpoint in patients treated with rivaroxaban compared with warfarin was consistent among patients with previous stroke or TIA ( 2·79 % rivaroxaban vs 2·96 % warfarin ; hazard ratio [ HR ] 0·94 , 95 % CI 0·77 - 1·16 ) and those without ( 1·44%vs 1·88 % ; 0·77 , 0·58 - 1·01 ; interaction p=0·23 ) . The number of major and non-major clinical ly relevant bleeding events per 100 person-years in patients treated with rivaroxaban compared with warfarin was consistent among patients with previous stroke or TIA ( 13·31 % rivaroxaban vs 13·87 % warfarin ; HR 0·96 , 95 % CI 0·87 - 1·07 ) and those without ( 16·69%vs 15·19 % ; 1·10 , 0·99 - 1·21 ; interaction p=0·08 ) . INTERPRETATION There was no evidence that the relative efficacy and safety of rivaroxaban compared with warfarin was different between patients who had a previous stroke or TIA and those who had no previous stroke or TIA . These results support the use of rivaroxaban as an alternative to warfarin for prevention of recurrent as well as initial stroke in patients with AF . FUNDING Johnson and Johnson Pharmaceutical Research and Development and Bayer HealthCare Background Aspirin , dipyridamole and clopidogrel are effective in secondary vascular prevention . Combination therapy with three antiplatelet agents might maximise the benefit of antiplatelet treatment  in the secondary prevention of ischaemic stroke . Methodology /Principal Findings A r and omised , parallel group , observer-blinded phase II trial compared the combination of aspirin , clopidogrel and dipyridamole with aspirin alone .  Adult patients with ischaemic stroke or transient ischaemic attack ( TIA ) within 5 years were included . The primary outcome was tolerability to treatment assessed as the number of patients completing r and omised treatment . Recruitment was halted prematurely after publication of the ESPRIT trial ( which confirmed that combined aspirin and dipyridamole is more effective than aspirin alone ) . 17 patients were enrolled : male 12 ( 71 % ) , mean age 62 ( SD 13 ) years , lacunar stroke syndrome 12 ( 71 % ) , median stroke/TIA onset to r and omisation 8 months . Treatment was discontinued in 4 of 9 ( 44 % ) patients receiving triple therapy vs. none of 8 taking aspirin ( p = 0.08 ) . One recurrent stroke occurred in a patient in the triple group who was noncompliant of all antiplatelet medications . The number of patients with adverse events and bleeding complications , and their severity , were significantly greater in the triple therapy group ( p<0.01 ) . Conclusions / Significance Long term triple antiplatelet therapy was asociated with a significant increase in adverse events and bleeding rates , and their severity , and a trend to increased discontinuations . However , the patients had a low risk of recurrence and future trials should focus on short term therapy in high risk patients characterised by a very recent event or failure of dual antiplatelet therapy . Trial Registration Controlled-Trials.com IS RCT AIM Prediabetes is an independent risk factor for future stroke . However , no effective treatment has yet been established for the recurrence of stroke in patients with prediabetes . Here we investigated the effects of pioglitazone , a potent peroxisome proliferator-activated receptor-gamma agonist , for the reduction of recurrent stroke in patients with prediabetes . METHODS Participants were patients who had a symptomatic ischemic stroke or transient ischemic attack ( TIA ) without a history of type 2 diabetes mellitus and who were diagnosed to have IGT or newly diagnosed diabetes by a 75-g oral glucose tolerance test . These patients were r and omized to either receive or not receive pioglitazone . The primary endpoint was a recurrence of ischemic stroke . RESULTS A total of 120 patients were enrolled in the study . Sixty-three patients received pioglitazone and 57 were enrolled in the control group that did not receive pioglitazone . The majority of patients ( 68.3 % ) were prescribed 15 mg of pioglitazone , while the remaining patients ( 31.7 % ) were treated with 30 mg of pioglitazone . Over a median follow-up period of 2.8 years , treatment with pioglitazone was found to be associated with a lower rate of the primary endpoint ( recurrence of stroke ) than that observed in the control group [ event rate=4.8 % pioglitazone vs 10.5 % control , hazard ratio=0.62 , 95 % confidence interval 0.13 - 2.35 , p=0.49 ] . However , differences were not statistically significant . CONCLUSIONS While this study was too underpowered to determine the effect of pioglitazone , the result failed to show beneficial effects in patients of ischemic stroke or TIA with impaired glucose tolerance and newly diagnosed diabetes BACKGROUND The risk of recurrent stroke is up to 10 % in the week after a transient ischaemic attack ( TIA ) or minor stroke . Modelling studies suggest that urgent use of existing preventive treatments could reduce the risk by 80 - 90 % , but in the absence of evidence many health-care systems make little provision . Our aim was to determine the effect of more rapid treatment after TIA and minor stroke in patients who are not admitted direct to hospital . METHODS We did a prospect i ve before ( phase 1 : April 1 , 2002 , to Sept 30 , 2004 ) versus after ( phase 2 : Oct 1 , 2004 , to March 31 , 2007 ) study of the effect on process of care and outcome of more urgent assessment and immediate treatment in clinic , rather than subsequent initiation in primary care , in all patients with TIA or minor stroke not admitted direct to hospital . The study was nested within a rigorous population -based incidence study of all TIA and stroke ( Oxford Vascular Study ; OXVASC ) , such that case ascertainment , investigation , and follow-up were complete and identical in both periods . The primary outcome was the risk of stroke within 90 days of first seeking medical attention , with independent blinded ( to study period ) audit of all events . FINDINGS Of the 1278 patients in OXVASC who presented with TIA or stroke ( 634 in phase 1 and 644 in phase 2 ) , 607 were referred or presented direct to hospital , 620 were referred for outpatient assessment , and 51 were not referred to secondary care . 95 % ( n=591 ) of all outpatient referrals were to the study clinic . Baseline characteristics and delays in seeking medical attention were similar in both periods , but median delay to assessment in the study clinic fell from 3 ( IQR 2 - 5 ) days in phase 1 to less than 1 ( 0 - 3 ) day in phase 2 ( p<0.0001 ) , and median delay to first prescription of treatment fell from 20 ( 8 - 53 ) days to 1 ( 0 - 3 ) day ( p<0.0001 ) . The 90-day risk of recurrent stroke in the patients referred to the study clinic was 10.3 % ( 32/310 patients ) in phase 1 and 2.1 % ( 6/281 patients ) in phase 2 ( adjusted hazard ratio 0.20 , 95 % CI 0.08 - 0.49 ; p=0.0001 ) ; there was no significant change in risk in patients treated elsewhere . The reduction in risk was independent of age and sex , and early treatment did not increase the risk of intracerebral haemorrhage or other bleeding . INTERPRETATION Early initiation of existing treatments after TIA or minor stroke was associated with an 80 % reduction in the risk of early recurrent stroke . Further follow-up is required to determine long-term outcome , but these results have immediate implication s for service provision and public education about TIA and minor stroke Background Survivors of transient ischemic attack ( TIA ) or stroke are at high risk for recurrent vascular events and aggressive treatment of vascular risk factors can reduce this risk . However , vascular risk factors , especially hypertension and high cholesterol , are not managed optimally even in those patients seen in specialized clinics . This gap between the evidence for secondary prevention of stroke and the clinical reality leads to suboptimal patient outcomes . In this study , we will be testing a pharmacist case manager for delivery of stroke prevention services . We hypothesize this new structure will improve processes of care which in turn should lead to improved outcomes . Methods We will conduct a prospect i ve , r and omized , controlled open-label with blinded ascertainment of outcomes ( PROBE ) trial . Treatment allocation will be concealed from the study personnel , and all outcomes will be collected in an independent and blinded manner by observers who have not been involved in the patient 's clinical care or trial participation and who are masked to baseline measurements . Patients will be  r and omized to control or a pharmacist case manager treating vascular risk factors to guideline -recommended target levels . Eligible patients will include all adult patients seen at stroke prevention clinics in Edmonton , Alberta after an ischemic stroke or TIA who have uncontrolled hypertension ( defined as systolic blood pressure ( BP ) > 140 mm Hg ) or dyslipidemia ( fasting LDL-cholesterol > 2.00 mmol/L ) and who are not cognitively impaired or institutionalized . The primary outcome will be the proportion of subjects who attain ' optimal BP and lipid control'(defined as systolic BP < 140 mm Hg and fasting LDL cholesterol < 2.0 mmol/L ) at six months compared to baseline ; 12-month data will also be collected for analyses of sustainability of any effects . A variety of secondary outcomes related to vascular risk and health-related quality of life will also be collected . Conclusions Nearly one-quarter of those who survive a TIA or minor stroke suffer another vascular event within a year . If our intervention improves the provision of secondary prevention therapies in these patients , the clinical ( and financial ) implication s will be enormous BACKGROUND Evidence is available on the effectiveness and costs of treatments to reduce stroke risk in long-term secondary prevention . However , there are few data on the costs and outcomes of urgent assessment and treatment after the onset of transient ischaemic attack ( TIA ) or minor stroke . The Early use of eXisting PREventive Strategies for Stroke ( EXPRESS ) study showed that urgent assessment and treatment reduced the 90-day risk of recurrent stroke by about 80 % . We now report the effect of the EXPRESS intervention on admissions to hospital , costs , and disability . METHODS EXPRESS was a prospect i ve population -based before ( phase 1 : April 1 , 2002 , to Sept 30 , 2004 ) versus after ( phase 2 : Oct 1 , 2004 , to March 31 , 2007 ) study of the effect of early assessment and treatment of TIA or minor stroke on the risk of early recurrent stroke . This report assesses the effect of the introduction of the phase 2 clinic on admissions to hospital within 90 days , hospital bed-days , hospital costs , and 6-month new disability ( progression from no disability before event [ modified Rankin scale score < or = 2 points ] to disability at 6 months [ modified Rankin scale score > 2 points ] ) or death , compared with the phase 1 clinic . To assess the main predictors of these outcomes , multivariate regression analyses were done . FINDINGS The 90-day risk of fatal or disabling stroke was reduced in phase 2 ( 1 of 281 vs 16 of 310 ; p=0.0005 ) . Hospital admissions for recurrent stroke were also lower in phase 2 than in phase 1 ( 5 vs 25 ; p=0.001 ) , which reduced the overall number of hospital bed-days compared with phase 1 ( 672 vs 1957 days ; p=0.017 ) . Hospital bed-days for admissions to hospital due to vascular causes were also lower in phase 2 ( 427 vs 1365 days ; p=0.016 ) , which generated savings of 624 pounds per patient referred to the phase 2 clinic ( p=0.028 ) . Results from the multivariate analyses showed that assessment in phase 2 was an independent predictor of reduced disability , days in hospital , and costs . INTERPRETATION Urgent assessment and treatment of patients with TIA or minor stroke who were referred to a specialist outpatient clinic reduced subsequent hospital bed-days , acute costs , and 6-month disability BACKGROUND AND PURPOSE Few community-based studies have examined the long-term risk of recurrent stroke after an acute first-ever stroke . This study aim ed to determine the absolute and relative risks of a first recurrent stroke over the first 5 years after a first-ever stroke and the predictors of such recurrence in a population -based series of people with first-ever stroke in Perth , Western Australia . METHODS Between February 1989 and August 1990 , all people with a suspected acute stroke or transient ischemic attack of the brain who were resident in a geographically defined region of Perth , Western Australia , with a population of 138 708 people , were registered prospect ively and assessed according to st and ardized diagnostic criteria . Patients were followed up prospect ively at 4 months , 12 months , and 5 years after the index event . RESULTS Three hundred seventy patients with a first-ever stroke were registered , of whom 351 survived > 2 days . Data were available for 98 % of the cohort at 5 years , by which time 199 patients ( 58 % ) had died and 52 ( 15 % ) had experienced a recurrent stroke , 12 ( 23 % ) of which were fatal within 28 days . The 5-year cumulative risk of first recurrent stroke was 22.5 % ( 95 % confidence limits [ CL ] , 16.8 % , 28.1 % ) . The risk of recurrent stroke was greatest in the first 6 months after stroke , at 8.8 % ( 95 % CL , 5.4 % , 12.1 % ) . After adjustment for age and sex , the prognostic factors for recurrent stroke were advanced , but not extreme , age ( 75 to 84 years ) ( hazard ratio [ HR ] , 2.6 ; 95 % CL , 1.1 , 6.2 ) , hemorrhagic index stroke ( HR , 2.1 ; 95 % CL , 0.98 , 4.4 ) , and diabetes mellitus ( HR , 2.1 ; 95 % CL , 0.95 , 4.4 ) . CONCLUSIONS Approximately 1 in 6 survivors ( 15 % ) of a first-ever stroke experience a recurrent stroke over the next 5 years , of which 25 % are fatal within 28 days . The pathological subtype of the recurrent stroke is the same as that of the index stroke in 88 % of cases . The predictors of first recurrent stroke in this study were advanced age , hemorrhagic index stroke , and diabetes mellitus , but numbers of recurrent events were modest . Because the risk of recurrent stroke is highest ( 8.8 % ) in the first 6 months after stroke , strategies for secondary prevention  should be initiated as soon as possible after the index event BACKGROUND Epidemiological studies suggest that raised plasma concentrations of total homocysteine might be a risk factor for major vascular events . Whether lowering total homocysteine with B vitamins prevents major vascular events in patients with previous stroke or transient ischaemic attack is unknown . We aim ed to assess whether the addition of once-daily supplements of B vitamins to usual medical care would lower total homocysteine and reduce the combined incidence of non-fatal stroke , non-fatal myocardial infa rct ion , and death attributable to vascular causes in patients with recent stroke or transient ischaemic attack of the brain or eye . METHODS In this r and omised , double-blind , parallel , placebo-controlled trial , we assigned patients with recent stroke or transient ischaemic attack ( within the past 7 months ) from 123 medical centres in 20 countries to receive one tablet daily of placebo or B vitamins ( 2 mg folic acid , 25 mg vitamin B6 , and 0.5 mg vitamin B12 ) . Patients were r and omly allocated by means of a central 24-h telephone service or an interactive website , and allocation was by use of r and om permuted blocks stratified by hospital . Participants , clinicians , carers , and investigators who assessed outcomes were masked to the assigned intervention . The primary endpoint was the composite of stroke , myocardial infa rct ion , or vascular death . All patients r and omly allocated to a group were included in the analysis of the primary endpoint . This trial is registered with Clinical Trials.gov , NCT00097669 , and Current Controlled Trials , IS RCT N74743444 . FINDINGS Between Nov 19 , 1998 , and Dec 31 , 2008 , 8164 patients were r and omly assigned to receive B vitamins ( n=4089 ) or placebo ( n=4075 ) . Patients were followed up for a median duration of 3.4 years ( IQR 2.0 - 5.5 ) . 616 ( 15 % ) patients assigned to B vitamins and 678 ( 17 % ) assigned to placebo reached the primary endpoint ( risk ratio [ RR ] 0.91 , 95 % CI 0.82 to 1.00 , p=0.05 ; absolute risk reduction 1.56 % , -0.01 to 3.16 ) . There were no unexpected serious adverse reactions and no significant differences in common adverse effects between the treatment groups . INTERPRETATION Daily administration of folic acid , vitamin B6 , and vitamin B12 to patients with recent stroke or transient ischaemic attack was safe but did not seem to be more effective than placebo in reducing the incidence of major vascular events . These results do not support the use of B vitamins to prevent recurrent stroke . The results of ongoing trials and an individual patient data meta- analysis will add statistical power and precision to present estimates of the effect of B vitamins . FUNDING Australia National Health and Medical Research Council , UK Medical Research Council , Singapore Biomedical Research Council , Singapore National Medical Research Council , Australia National Heart Foundation , Royal Perth Hospital Medical Research Foundation , and Health Department of Western Australia Background and Purpose : & bgr;‐Blockers prevent vascular events in patients after myocardial infa rct ion and lower blood pressure , the main risk factor for stroke . Hence , we assessed the effects of atenolol on the occurrence of death from vascular causes , stroke , or myocardial infa rct ion and on blood pressure in patients after a transient ischemic attack or nondisabling ischemic stroke . Methods : In a double‐blind , placebo‐controlled r and omized clinical trial we studied the occurrence of the outcome event death from vascular causes , nonfatal stroke , or nonfatal myocardial infa rct ion and the outcome event fatal or nonfatal stroke as well as blood pressure on follow‐up . A total of 1,473 aspirin‐treated patients with transient ischemic attack or nondisabling ischemic stroke were r and omized to 50 mg atenolol daily or placebo . The mean follow‐up was 2.6 years . Results : Patients on atenolol had a risk of 97/732 ( 13.3 % ) for the combined outcome event versus a risk of 95/741 ( 12.8 % ) for those on placebo ( adjusted hazard ratio , 1.00 ; 95 % confidence interval , 0.76‐1.33 ) . The adjusted hazard ratio for fatal or nonfatal stroke was 0.82 ( 95 % confidence interval , 0.57‐1.19 ) . More patients on & bgr;‐blocker ( 153 ) reported adverse effects than on placebo ( 103 ) . At the first follow‐up visit after r and omization ( median at 4 months ) systolic blood pressure in the atenolol group had dropped by 8.0 mm Hg compared with 2.2 mm Hg in the placebo group ( difference , 5.8 mm Hg ; 95 % confidence interval , 2.9‐8.6 mm Hg ) . For diastolic blood pressure this difference was 2.9 mm Hg ( 95 % confidence interval , 1.5‐4.4 mm Hg ) . Conclusions : Our data neither confirm nor rule out that atenolol prevents important vascular events in patients after transient ischemic attack or nondisabling ischemic stroke , given the modest effect on blood pressure , the restrictions in patient selection , and the limited number of patient‐years . ( Stroke 1993;24:543‐548
For other outcomes analysed ( major vascular events , death from all causes , death from cardiovascular causes ) , we observed no significant differences between the groups .
There were minor blood pressure reductions in the intervention group .
To date , no available evidence supports the routine use of beta-blockers for secondary prevention after stroke or TIA .
BACKGROUND Stroke affects 15 million people per year worldwide .
Despite recent developments in acute stroke treatment , prevention remains very important .
Stroke has a high rate of recurrence ; therefore secondary prevention is also important .
Many clinical approaches to control risk factors have been proposed .
One of these approaches is the prescription of beta-blockers that have effects beyond the reduction of blood pressure , which can reduce the recurrence of stroke .
OBJECTIVES To evaluate the efficacy of beta-blockers for preventing stroke recurrence and for reducing death and major vascular events in people with a previous stroke or transient ischaemic attack ( TIA ) , and to determine their safety , particularly with regard to the development of diabetes mellitus .