G.S. Venables

Effectiveness of thigh-length graduated compression stockings to reduce the risk of deep vein thrombosis after stroke (CLOTS trial 1): a multicentre, randomised controlled trial.

Summary Background Deep vein thrombosis (DVT) and pulmonary embolism are common after stroke. In small trials of patients undergoing surgery, graduated compression stockings (GCS) reduce the risk of DVT. National stroke guidelines extrapolating from these trials recommend their use in patients with stroke despite insufficient evidence. We assessed the effectiveness of thigh-length GCS to reduce DVT after stroke. Methods In this outcome-blinded, randomised controlled trial, 2518 patients who were admitted to hospital within 1 week of an acute stroke and who were immobile were enrolled from 64 centres in the UK, Italy, and Australia. Patients were allocated via a central randomisation system to routine care plus thigh-length GCS (n=1256) or to routine care plus avoidance of GCS (n=1262). A technician who was blinded to treatment allocation undertook compression Doppler ultrasound of both legs at about 7–10 days and, when practical, again at 25–30 days after enrolment. The primary outcome was the occurrence of symptomatic or asymptomatic DVT in the popliteal or femoral veins. Analyses were by intention to treat. This study is registered, number ISRCTN28163533. Findings All patients were included in the analyses. The primary outcome occurred in 126 (10·0%) patients allocated to thigh-length GCS and in 133 (10·5%) allocated to avoid GCS, resulting in a non-significant absolute reduction in risk of 0·5% (95% CI −1·9% to 2·9%). Skin breaks, ulcers, blisters, and skin necrosis were significantly more common in patients allocated to GCS than in those allocated to avoid their use (64 [5%] vs 16 [1%]; odds ratio 4·18, 95% CI 2·40–7·27). Interpretation These data do not lend support to the use of thigh-length GCS in patients admitted to hospital with acute stroke. National guidelines for stroke might need to be revised on the basis of these results. Funding Medical Research Council (UK), Chief Scientist Office of Scottish Government, Chest Heart and Stroke Scotland, Tyco Healthcare (Covidien) USA, and UK Stroke Research Network.

Long-term risk of carotid restenosis in patients randomly assigned to endovascular treatment or endarterectomy in the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS): long-term follow-up of a randomised trial

Summary Background In the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS), early recurrent carotid stenosis was more common in patients assigned to endovascular treatment than it was in patients assigned to endarterectomy (CEA), raising concerns about the long-term effectiveness of endovascular treatment. We aimed to investigate the long-term risks of restenosis in patients included in CAVATAS. Methods 413 patients who were randomly assigned in CAVATAS and completed treatment for carotid stenosis (200 patients had endovascular treatment and 213 patients had endarterectomy) had prospective clinical follow-up at a median of 5 years and carotid duplex ultrasound at a median of 4 years. We investigated the cumulative long-term incidence of carotid restenosis after endovascular treatment and endarterectomy, the effect of the use of stents on restenosis after endovascular treatment, risk factors for the development of restenosis, and the effect of carotid restenosis on the risk of recurrent cerebrovascular events. Analysis was by intention to treat. This study is registered, number ISRCTN01425573. Findings Severe carotid restenosis (≥70%) or occlusion occurred significantly more often in patients in the endovascular arm than in patients in the endarterectomy arm (adjusted hazard ratio [HR] 3·17, 95% CI 1·89–5·32; p<0·0001). The estimated 5-year incidence of restenosis was 30·7% in the endovascular arm and 10·5% in the endarterectomy arm. Patients in the endovascular arm who were treated with a stent (n=50) had a significantly lower risk of developing restenosis of 70% or greater compared with those treated with balloon angioplasty alone (n=145; HR 0·43, 0·19–0·97; p=0·04). Current smoking or a history of smoking was a predictor of restenosis of 70% or more (2·32, 1·19–4·54; p=0·01) and the early finding of moderate stenosis (50–69%) up to 60 days after treatment was associated with the risk of progression to restenosis of 70% or more (3·76, 1·88–7·52; p=0·0002). The composite endpoint of ipsilateral non-perioperative stroke or transient ischaemic attack occurred more often in patients in whom restenosis of 70% or more was diagnosed in the first year after treatment compared with patients without restenosis of 70% or more (5-year incidence 23% vs 11%; HR 2·18, 1·04–4·54; p=0·04), but the increase in ipsilateral stroke alone was not significant (10% vs 5%; 1·67, 0·54–5·11). Interpretation Restenosis is about three times more common after endovascular treatment than after endarterectomy and is associated with recurrent ipsilateral cerebrovascular symptoms; however, the risk of recurrent ipsilateral stroke is low. Further data are required from on-going trials of stenting versus endarterectomy to ascertain whether long-term ultrasound follow-up is necessary after carotid revascularisation. Funding British Heart Foundation; UK National Health Service Management Executive; UK Stroke Association.

Endovascular treatment with angioplasty or stenting versus endarterectomy in patients with carotid artery stenosis in the Carotid And Vertebral Artery Transluminal Angioplasty Study (CAVATAS): long-term follow-up of a randomised trial

Summary Background Endovascular treatment (angioplasty with or without stenting) is an alternative to carotid endarterectomy for carotid artery stenosis but there are scarce long-term efficacy data showing that it prevents stroke. We therefore report the long-term results of the Carotid and Vertebral Artery Transluminal Angioplasty Study (CAVATAS). Methods Between March, 1992, and July, 1997, patients who presented at a participating centre with a confirmed stenosis of the internal carotid artery that was deemed equally suitable for either carotid endarterectomy or endovascular treatment were randomly assigned to either treatment in equal proportions by telephone or fax from the randomisation service at the Oxford Clinical Trials Unit, UK. Patients were seen by an independent neurologist at 1 and 6 months after treatment and then every year after randomisation for as long as possible, up to a maximum of 11 years. Major outcome events were transient ischaemic attack, non-disabling, disabling, and fatal stroke, myocardial infarction, and death from any other cause. Outcomes were adjudicated on by investigators who were masked to treatment. Analysis was by intention to treat. This study is registered, number ISRCTN 01425573. Findings 504 patients with stenosis of the carotid artery (90% symptomatic) were randomly assigned to endovascular treatment (n=251) or surgery (n=253). Within 30 days of treatment, there were more minor strokes that lasted less than 7 days in the endovascular group (8 vs 1) but the number of other strokes in any territory or death was the same (25 vs 25). There were more cranial nerve palsies (22 vs 0) in the endarterectomy group than in the endovascular group. Median length of follow up in both groups was 5 years (IQR 2–6). By comparing endovascular treatment with endarterectomy after the 30-day post-treatment period, the 8-year incidence and hazard ratio (HR) at the end of follow-up for ipsilateral non-perioperative stroke was 11·3% versus 8·6% (HR 1·22, 95% CI 0·59–2·54); for ipsilateral non-perioperative stroke or TIA was 19·3% versus 17·2% (1·29, 0·78–2·14); and for any non-perioperative stroke was 21·1% versus 15·4% (1·66, 0·99–2·80). Interpretation More patients had stroke during follow-up in the endovascular group than in the surgical group, but the rate of ipsilateral non-perioperative stroke was low in both groups and none of the differences in the stroke outcome measures was significant. However, the study was underpowered and the confidence intervals were wide. More long-term data are needed from the on going stenting versus endarterectomy trials. Funding British Heart Foundation; UK National Health Service Management Executive; UK Stroke Association.

Thigh-length versus below-knee stockings for deep venous thrombosis prophylaxis after stroke: a randomized trial

BACKGROUND Graduated compression stockings are widely used for deep venous thrombosis (DVT) prophylaxis. Although below-knee stockings are used more often than thigh-length stockings, no reliable evidence indicates that they are as effective as thigh-length stockings. OBJECTIVE To compare the effectiveness of thigh-length stockings with that of below-knee stockings for preventing proximal DVT in immobile, hospitalized patients with stroke. DESIGN Parallel-group trial with centralized randomization (minimization within centers) to ensure allocation concealment. The ultrasonographers who looked for DVT were blinded, but the patients and caregivers were not. (Controlled-trials.com registration number: ISRCTN28163533) SETTING 112 hospitals in 9 countries. PATIENTS 3114 immobile patients hospitalized with acute stroke between January 2002 and May 2009. INTERVENTION 1552 patients received thigh-length stockings and 1562 patients received below-knee stockings to wear while they were in the hospital. MEASUREMENTS Ultrasonographers performed compression duplex ultrasonography in 1406 patients (96% of survivors) in each treatment group between 7 and 10 days after enrollment. They performed a second scan in 643 patients in the thigh-length stockings group and 639 in the below-knee stockings group at about 25 to 30 days. The primary outcome was symptomatic or asymptomatic DVT in the popliteal or femoral veins, detected on either scan. RESULTS Patients were retained in their assigned group for all analyses. The primary outcome occurred in 98 patients (6.3%) who received thigh-length stockings and 138 (8.8%) who received below-knee stockings (absolute difference, 2.5 percentage points [95% CI, 0.7 to 4.4 percentage points]; P = 0.008), an odds reduction of 31% (CI, 9% to 47%). Seventy-five percent of patients in both groups wore the stockings for 30 days or until they were discharged, died, or regained mobility. Skin breaks occurred in 61 patients who received thigh-length stockings (3.9%) and 45 (2.9%) who received below-knee stockings. LIMITATION Blinding was incomplete, 2 scans were not obtained for all enrolled patients, and the trial was stopped before the target accrual was reached. CONCLUSION Proximal DVT occurs more often in patients with stroke who wear below-knee stockings than in those who wear thigh-length stockings. PRIMARY FUNDING SOURCE Medical Research Council of the United Kingdom, Chief Scientist Office of the Scottish Government, and Chest Heart and Stroke Scotland.

Stroke management in Europe

Stroke is a leading cause of death and disability in Europe. Standards of care vary widely, and the introduction of simple standards will improve mortality and morbidity. It has been shown, in the absence of any medical treatment for acute stroke, that improving the organization of care for people with stroke significantly improves outcome. Recommendations are made for simple changes to the organization of care. Preventative measures after first stroke reduce incidence of subsequent stroke; these could be made widely available. Rehabilitation for those with persisting disability should be patient centred and commence immediately after the patient is alert and medically stable. Urgent research is required to find out which components of rehabilitation are important, and measures should be in place to ensure that all who require rehabilitation receive it from appropriately trained professionals. Population‐based monitoring systems covering incidence, case fatality, mortality and disability should be put in place in all European Member States by the year 2005.

Predictors of major vascular events in patients with a transient ischemic attack or minor ischemic stroke and with nonrheumatic atrial fibrillation

BACKGROUND AND PURPOSE The risk of major vascular events after an initial episode of cerebral ischemia in patients with nonrheumatic atrial fibrillation (NRAF) varies from 2% to 15% in the first year and is approximately 5% yearly thereafter. Few studies have reported on risk factors that can be used to identify high-risk subgroups within this patient population. METHODS We studied the predictive value of several easily obtainable clinical characteristics in a group of 375 placebo-treated patients with NRAF and a recent episode of transient or nondisabling cerebral ischemia who were entered in a multicenter clinical trial. The mean follow-up was 1.6 years. RESULTS By means of multivariate modeling, six independent variables were identified: history of previous thromboembolism, ischemic heart disease, enlarged cardiothoracic ratio on chest roentgenogram, systolic blood pressure greater than 160 mm Hg at study entry, NRAF for more than 1 year, and presence of an ischemic lesion on CT scan. These variables could also be used to stratify patients in low-, medium-, and high-risk subgroups for the other two arms of the trial, those treated with anticoagulation and aspirin. Patients older than 75 years with three or more risk factors seemingly benefited less from both aspirin and anticoagulant treatment. CONCLUSIONS Easily obtainable patient characteristics are helpful in estimating the potential effect of adequate secondary prevention in patients with NRAF who recently suffered a transient ischemic attack or minor ischemic stroke.

Filter-Protected versus Unprotected Carotid Artery Stenting: A Randomised Trial

Background: Our aim was to determine whether filter protection reduces embolisation to the brain during carotid artery stenting (CAS). Methods: Thirty patients with symptomatic carotid artery stenosis ≧70% (North American Symptomatic Carotid Endarterectomy Trial) were randomly assigned to filter-protected or unprotected CAS. Diffusion-weighted magnetic resonance imaging (DWI) of the brain was performed before and at 3 time points after CAS. In a subset of patients, high-intensity transient signals on transcranial Doppler (TCD) were recorded with categorisation of emboli. Data were independently reviewed off-site. Results: There were no significant differences in mean age, proportion of octogenarians or presenting symptoms between the groups. On procedural DWI (1–3 and 24 h after stenting), there were 7/24 (29%) and 4/22 (18%) new lesions in protected and unprotected patients respectively (p = 0.38). At 30 days there were 9/33 (26%) and 4/33 (12%) lesions in protected and unprotected patients, respectively (p = 0.1). On TCD there were significantly more signals in total as well as particulate emboli during filter-protected CAS (426.5 and 251.3) than during unprotected CAS (165.2 and 92) – p = 0.01 and 0.03, respectively. Conclusions: Filter-protected CAS is associated with an increase in new lesions on DWI and significantly higher rates of total and particulate microembolisation on TCD than unprotected CAS. The clinical significance of these findings requires further study.

Effect of Treatment of Carotid Artery Stenosis on Blood Pressure A Comparison of Hemodynamic Disturbances After Carotid Endarterectomy and Endovascular Treatment

Background and Purpose— Carotid intervention by carotid endarterectomy (CEA) or endovascular treatment may cause hemodynamic change. The immediate and long-term effects on blood pressure after these procedures were assessed. Methods— Patients were randomized to CEA (n=49) or endovascular treatment (n=55) that comprised percutaneous transluminal angioplasty alone (n=31), balloon-expandable stent (n=13), or self-expandable stent (n=11). A baseline 24-hour ambulatory blood pressure recording was made before carotid intervention and repeated at 24 hours, 1 month, and 6 months after the procedure. Results— In the first 24 hours after the procedure, episodes of hypotension occurred in 75% of the CEA group and 76% of the endovascular group; hypertension occurred in 11% and 13%, respectively. There was a significant fall in blood pressure at 1 hour after the procedure in both groups (24 and 16 mm Hg fall in CEA and endovascular groups, respectively), but this was only sustained in the endovascular group. The pattern of blood pressure response in the first 24 hours was significantly different (P <0.0001, ANCOVA). Systolic blood pressure was significantly lower at 1 and 6 months only in the surgical group (6 and 5 mm Hg fall, respectively). Conclusions— Both CEA and endovascular treatment have an effect on blood pressure stability, particularly within the first 24 hours after the procedure.

Timing and frequency of complications after carotid artery stenting: what is the optimal period of observation?☆

OBJECTIVE Currently our standard of practice is that patients undergoing carotid artery stenting (CAS) may be safely discharged on the first day post-procedure. However, many patients are completely independent on the evening of procedure. Therefore we sought to establish the safety and feasibility of same-day discharge by assessing frequency and time of complications in the first 30 days after CAS. METHOD Case records for 208 consecutive patients who had undergone CAS from October 1999 to October 2002 were retrospectively reviewed. Excluded were four cases in which combined CAS and carotid endarterectomy was performed to treat synchronous stenosis. Of the remaining 204 cases, involving 201 patients (three patients underwent staged bilateral CAS), 173 (84.8%) were symptomatic and 31 (15.2%) were asymptomatic. RESULT Thirty-eight major events or death (inclusive of all neurologic events and any complications that required treatment) were recorded in the first 30 days after CAS, for an event rate of 18.6% per case. These were 7 (3.4%) major access site complications; 18 (8.8%) neurologic events, of which 10 (4.9%) were transient ischemic events and 8 (3.9%) were strokes (including minor, major, and fatal stroke); 8 (3.9%) cardiovascular complications; and five (2.5%) other events. Twenty (52.6%) events occurred in the first 6 hours after CAS, 2 (5.3%) between 6 and 12 hours, 3 (7.9%) between 12 and 24 hours, and 13 (34.2%) 24 hours to 30 days post procedure. Four (2.0%) deaths were recorded in this period, 1 secondary to stroke, 1 from a perforated myocardium from a temporary pacing wire, and 2 from unrelated causes. The 30-days stroke and death rate was 5.4% (11 of 204 patients). CONCLUSION Time of complications suggests that outpatient performance of CAS is feasible and safe in selected patients.

Update on the third international stroke trial (IST-3) of thrombolysis for acute ischaemic stroke and baseline features of the 3035 patients recruited

BackgroundIntravenous recombinant tissue plasminogen activator (rtPA) is approved in Europe for use in patients with acute ischaemic stroke who meet strictly defined criteria. IST-3 sought to improve the external validity and precision of the estimates of the overall treatment effects (efficacy and safety) of rtPA in acute ischaemic stroke, and to determine whether a wider range of patients might benefit.DesignInternational, multi-centre, prospective, randomized, open, blinded endpoint (PROBE) trial of intravenous rtPA in acute ischaemic stroke. Suitable patients had to be assessed and able to start treatment within 6 hours of developing symptoms, and brain imaging must have excluded intracranial haemorrhage and stroke mimics.ResultsThe initial pilot phase was double blind and then, on 01/08/2003, changed to an open design. Recruitment began on 05/05/2000 and closed on 31/07/2011, by which time 3035 patients had been included, only 61 (2%) of whom met the criteria for the 2003 European approval for thrombolysis. 1617 patients were aged over 80 years at trial entry. The analysis plan will be finalised, without reference to the unblinded data, and published before the trial data are unblinded in early 2012. The main trial results will be presented at the European Stroke Conference in Lisbon in May 2012 with the aim to publish simultaneously in a peer-reviewed journal. The trial result will be presented in the context of an updated Cochrane systematic review. We also intend to include the trial data in an individual patient data meta-analysis of all the relevant randomised trials.ConclusionThe data from the trial will: improve the external validity and precision of the estimates of the overall treatment effects (efficacy and safety) of iv rtPA in acute ischaemic stroke; provide: new evidence on the balance of risk and benefit of intravenous rtPA among types of patients who do not clearly meet the terms of the current EU approval; and, provide the first large-scale randomised evidence on effects in patients over 80, an age group which had largely been excluded from previous acute stroke trials.Trial registrationISRCTN25765518