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Extensive Leukoaraiosis Is Associated With High Early Risk of Recurrence After Ischemic Stroke [Clinical Sciences]

Lun, 01/27/2014 - 21:02
Background and Purpose—

The integrity of white matter tracts connecting different parts of the brain is important for rapid compensation for the lost function from ischemic stroke. Impaired white matter reserve capacity secondary to leukoaraiosis may facilitate detection of new symptomatic ischemic events that would otherwise remain inconspicuous after an initial ischemic stroke. We sought to identify whether the extent of leukoaraiosis was a predictor of risk of early stroke recurrence.

Methods—

We used Cox regression analysis in consecutive patients with ischemic stroke to determine the relationship between leukoaraiosis burden and symptomatic stroke recurrence within 90 days. We graded total leukoaraiosis, periventricular leukoaraiosis, and subcortical leukoaraiosis using the Fazekas scale as mild (<2) and extensive (≥2) on fluid-attenuated inversion recovery images obtained within 72 hours of stroke onset in the hemisphere contralateral to acute stroke.

Results

—There were 106 recurrent events in 2378 patients. The cumulative incidence of recurrence was 5.9% at 90 days. Kaplan–Meier estimate of recurrence-free survival rate was lower in patients with extensive leukoaraiosis (P=0.04) and extensive periventricular leukoaraiosis (P=0.02) but not in extensive subcortical leukoaraiosis (P=0.09). Multivariable Cox regression analysis revealed a hazard ratio of 1.50 (95% confidence interval, 1.00–2.25) for extensive leukoaraiosis, 1.67 (95% confidence interval, 1.11–2.51) for extensive periventricular leukoaraiosis, and 1.42 (95% confidence interval, 0.94–2.12) for extensive subcortical leukoaraiosis.

Conclusions—

The extent of leukoaraiosis independently predicts 90-day recurrent stroke risk after ischemic stroke. This suggests that leukoaraiosis may be used for risk stratification in ischemic stroke.

Mild Hypothermia After Intravenous Thrombolysis in Patients With Acute Stroke: A Randomized Controlled Trial [Clinical Sciences]

Lun, 01/27/2014 - 21:02
Background and Purpose—

Hypothermia improves outcome in resuscitated patients and newborns with hypoxic brain injury. We studied the safety and feasibility of mild hypothermia in awake patients with stroke after intravenous thrombolysis.

Methods—

Patients were randomized 1:1 to mild hypothermia (35°C) or to standard stroke unit care within 6 hours of symptom onset. Hypothermia was induced with a surface-cooling device and cold saline infusions. Active cooling was restrained gradually after 12 hours at <35.5°C. The primary outcome measure was the number of patients with <36°C body temperature for >80% of the 12-hour cooling period.

Results—

We included 36 patients with a median of National Institutes of Health Stroke Scale score of 9 one hour after thrombolysis. Fifteen of 18 (83%) patients achieved the primary end point. Sixteen (89%) patients reached <35.5°C in a median time of 10 hours (range, 7–16 hours) from symptom onset, spent 10.5 hours (1–17 hours) in hypothermia, and were back to normothermia in 23 hours (15–29 hours). Few serious adverse events were more common in the hypothermia group. At 3 months, 7 patients (39%) in both groups had good outcome (modified Ranking Scale, 0–2), whereas poor outcome (modified Ranking Scale, 4–6) was twice as common in the normothermia group (44% versus 22%).

Conclusions—

Mild hypothermia with a surface-cooling device in an acute stroke unit is safe and feasible in thrombolyzed, spontaneously breathing patients with stroke, despite the adverse events.

Clinical Trial Registration—

URL: http://www.clinicaltrials.gov. Unique identifier: NCT00987922.

Antiplatelet Treatment for Prevention of Cerebrovascular Events in Patients With Vascular Diseases: A Systematic Review and Meta-Analysis [Clinical Sciences]

Lun, 01/27/2014 - 21:02
Background and Purpose—

The efficacy and safety of different antiplatelet regimes for prevention of stroke in patients at high risk were investigated in a systematic review and meta-analysis.

Methods—

We searched the Cochrane Central Register of Controlled Trials, MEDLINE, and Web of Science. Twenty-two studies comprising 173 371 patients were included.

Results—

In the overall population, dual antiplatelet therapy (DAPT) with aspirin and clopidogrel in comparison to aspirin monotherapy reduced the relative risk of total stroke by 20% (risk ratio [RR], 0.80; 95% confidence interval [CI], 0.73–0.88; P<0.0001; I2=28%) and of ischemic stroke or transient ischemic attack by 23% (RR, 0.77; 95% CI, 0.69–0.85; P<0.0001; I2=18%) without increasing the risk of intracranial hemorrhage. In the secondary prevention cohort, DAPT with aspirin and clopidogrel also reduced the relative risk of total stroke by 24% as compared with aspirin alone (RR, 0.76; 95% CI, 0.68–0.86; P<0.0001; I2=0%). DAPT with prasugrel or ticagrelor and aspirin versus DAPT with clopidogrel and aspirin was not associated with a risk reduction of stroke.

Conclusions—

DAPT with clopidogrel and aspirin compared with aspirin effectively reduces the risk of total and ischemic stroke in the overall cohort consisting of patients with cardiovascular disease without increase in intracranial hemorrhage, as well as decreases the risk of a recurrent total stroke in patients with a previous stroke/transient ischemic attack. Our meta-analysis suggests that DAPT including low-dose aspirin (75–100 mg) and clopidogrel (75 mg) should be further investigated as a strategy to reduce recurrent strokes.

Clinical Trial Registration—

URL: http://www.crd.york.ac.uk/prospero. Unique identifier: CRD42011001596.

Improving Door-to-Needle Times: A Single Center Validation of the Target Stroke Hypothesis [Clinical Sciences]

Lun, 01/27/2014 - 21:02
Background and Purpose—

National guidelines recommend imaging within 25 minutes of emergency department arrival and intravenous tissue-type plasminogen activator within 60 minutes of emergency department arrival for patients with acute stroke. In 2007, we implemented a new institutional acute stroke care model to include 10 best practices and evaluated the effect of this intervention on improving door-to-computed tomography (CT) and door-to-needle (DTN) times at our hospital.

Methods—

We compared patients who presented directly to our hospital with acute ischemic stroke in the preintervention (2003–2006) and postintervention (2008–2011) periods. We did not include 2007, the year that the new protocol was established. Predictors of DTN ≤60 minutes before and after the intervention were assessed using 2 for categorical variables, and t test and Wilcoxon signed-rank test for continuous variables.

Results—

Among 2595 patients with acute stroke, 284 (11%) received intravenous tissue-type plasminogen activator. For patients arriving within an intravenous tissue-type plasminogen activator window, door-to-CT <25 improved from 26.7% pre intervention to 52.3% post intervention (P<0.001). Similarly, the percentage of patients with DTN <60 doubled from 32.4% to 70.3% (P<0.001). Patients with DTN ≤60 did not differ significantly with respect to demographics, comorbidities, or National Institutes of Health Stroke Scale score in comparison with those treated after 60 minutes.

Conclusions—

Door-to-CT and DTN times improved dramatically after applying 10 best practices, all of which were later incorporated into the Target Stroke Guidelines created by the American Heart Association. The only factor that significantly affected DTN60 was the intervention itself, indicating that these best practices can result in improved DTN times.

Dose-Related Effects of Statins on Symptomatic Intracerebral Hemorrhage and Outcome After Thrombolysis for Ischemic Stroke [Clinical Sciences]

Lun, 01/27/2014 - 21:02
Background and Purpose—

The aim of our study was to assess whether statins have dose-dependent effects on risk of symptomatic intracerebral hemorrhage (sICH) and outcome after intravenous thrombolysis for ischemic stroke.

Methods—

We pooled data from 2 European intravenous thrombolysis registries. Statin doses were stratified in 3 groups according to the attainable lowering of cholesterol levels (low dose: simvastatin 20 mg or equivalent; medium dose: simvastatin 40 mg or equivalent; and high dose: simvastatin 80 mg or equivalent). sICH was defined according to the European Cooperative Acute Stroke Study. Modified Rankin Scale score 0 to 2 at 3 months was considered a favorable outcome.

Results—

Among 1446 patients analyzed (median age, 75 years; median initial National Institutes of Health Stroke Scale score, 11; 54% men), 317 (22%) used statins before intravenous thrombolysis. Of them, 120 patients had low-dose, 134 medium-dose, and 63 high-dose statin therapy. sICH occurred in 4% of patients (n=53). Frequency of sICH was 2%, 6%, and 13% in patients with low-, medium-, and high-dose statin treatment, respectively (P<0.01). Adjusted odds ratio (OR) for sICH was 2.4 (95% confidence interval [CI], 1.1–5.3) and 5.3 (95% CI, 2.3–12.3) for patients with medium- and high-dose statins compared with non–statin users. Statin users more often achieved favorable outcome compared with non–statin users (58% versus 51%; P=0.03). An independent association of statin use with favorable outcome was detected (adjusted OR, 1.8; 95% CI, 1.3–2.5). The association was maintained when stratifying for statin dose, although it was not significant in the high-dose group anymore (OR, 1.7; 95% CI, 0.9–3.2).

Conclusions—

We observed an association between increasing dose of statin use and risk of sICH after intravenous thrombolysis. Nevertheless, there was an overall beneficial effect of previous statin use on favorable 3-month outcome.

Implementation of a Structured Guideline-Based Program for the Secondary Prevention of Ischemic Stroke in China [Clinical Sciences]

Lun, 01/27/2014 - 21:02
Background and Purpose—

High rates of ischemic stroke and poor adherence to secondary prevention measures are observed in the Chinese population.

Methods—

We used a national, multicenter, cluster-randomized controlled trial in which 47 hospitals were randomized to either a structured care program group (n=23) or a usual care group (n=24). The structured care program consisted of a specialist-administered, guideline-recommended pharmaceutical treatment and a lifestyle modification algorithm associated with written and Internet-accessed educational material for patients for the secondary prevention of ischemic stroke. The primary efficacy outcome was the proportion of patients who adhered to the recommended measures at 12-month postdischarge. This trial is registered with ClinicalTrial.gov (NCT00664846).

Results—

At 12 months, 1287 (72.1%) patients in the Standard Medical Management in Secondary Prevention of Ischemic Stroke in China (SMART) group and 1430 (72%) patients in the usual care group had completed the 12-month follow-up (P=0.342). Compared with the usual care group, those in the SMART group showed higher adherence to statins (56% versus 33%; P=0.006) but no difference in adherence to antiplatelet (81% versus 75%; P=0.088), antihypertensive (67% versus 69%; P=0.661), or diabetes mellitus drugs (73% versus 67%; P=0.297). No significant difference in the composite end point (new-onset ischemic stroke, hemorrhagic stroke, acute coronary syndrome, and all-cause death) was observed (3.56% versus 3.59%; P=0.921).

Conclusions—

The implementation of a program to improve adherence to secondary ischemic stroke prevention efforts in China is feasible, but these programs had only a limited impact on adherence and no impact on 1-year outcomes. Further development of a structured program to reduce vascular events after stroke is needed.

Clinical Trial Registration—URL: http://www.clinicaltrials.gov. Unique identifier: NCT00664846.

Detection of Atrial Fibrillation After Ischemic Stroke or Transient Ischemic Attack: A Systematic Review and Meta-Analysis [Clinical Sciences]

Lun, 01/27/2014 - 21:02
Background and Purpose—

Atrial fibrillation (AF) confers a high risk of recurrent stroke, although detection methods and definitions of paroxysmal AF during screening vary. We therefore undertook a systematic review and meta-analysis to determine the frequency of newly detected AF using noninvasive or invasive cardiac monitoring after ischemic stroke or transient ischemic attack.

Methods—

Prospective observational studies or randomized controlled trials of patients with ischemic stroke, transient ischemic attack, or both, who underwent any cardiac monitoring for a minimum of 12 hours, were included after electronic searches of multiple databases. The primary outcome was detection of any new AF during the monitoring period. We prespecified subgroup analysis of selected (prescreened or cryptogenic) versus unselected patients and according to duration of monitoring.

Results—

A total of 32 studies were analyzed. The overall detection rate of any AF was 11.5% (95% confidence interval, 8.9%–14.3%), although the timing, duration, method of monitoring, and reporting of diagnostic criteria used for paroxysmal AF varied. Detection rates were higher in selected (13.4%; 95% confidence interval, 9.0%–18.4%) than in unselected patients (6.2%; 95% confidence interval, 4.4%–8.3%). There was substantial heterogeneity even within specified subgroups.

Conclusions—

Detection of AF was highly variable, and the review was limited by small sample sizes and marked heterogeneity. Further studies are required to inform patient selection, optimal timing, methods, and duration of monitoring for detection of AF/paroxysmal AF.

Carotid Stenting: Is There an Operator Effect? A Pooled Analysis From the Carotid Stenting Trialists' Collaboration [Clinical Sciences]

Lun, 01/27/2014 - 21:02
Background and Purpose—

Randomized clinical trials show higher 30-day risk of stroke or death after carotid artery stenting compared with surgery. We examined whether operator experience is associated with 30-day risk of stroke or death in the Carotid Stenting Trialists’ Collaboration database.

Methods—

The Carotid Stenting Trialists’ Collaboration is a pooled individual patient database including all patients recruited in 3 randomized trials of stenting versus endarterectomy for symptomatic carotid stenosis (Endarterectomy Versus Angioplasty in patients with Symptomatic Severe Carotid Stenosis trial, Stent-Protected Angioplasty versus Carotid Endarterectomy trial, and International Carotid Stenting Study). Lifetime carotid artery stenting experience, lifetime experience in stenting procedures excluding the carotid, and annual number of procedures performed within the trial (in-trial volume), divided into tertiles, were used to measure operator experience. The outcome event was the occurrence of any stroke or death within 30 days of the procedure. The analysis was done per protocol.

Results—

Among 1546 patients who underwent carotid artery stenting, 120 (7.8%) had a stroke or death within 30 days of the procedure. The 30-day risk of stroke or death did not differ according to operator lifetime carotid artery stenting experience (P=0.8) or operator lifetime stenting experience excluding the carotid (P=0.7). In contrast, the 30-day risk of stroke or death was significantly higher in patients treated by operators with low (mean ≤3.2 procedures/y; risk 10.1%; adjusted risk ratio=2.30 [1.36–3.87]) and intermediate annual in-trial volumes (3.2–5.6 procedures/y; 8.4%; adjusted risk ratio=1.93 [1.14–3.27]) compared with patients treated by high annual in-trial volume operators (>5.6 procedures/y; 5.1%).

Conclusions—

Carotid stenting should only be performed by operators with annual procedure volume ≥6 cases per year.