Aspirin and extended-release dipyridamole versus clopidogrel for recurrent stroke

Background Recurrent stroke is a frequent, disabling event after ischemic stroke. This study compared the efficacy and safety of two antiplatelet regimens — aspirin plus extendedrelease dipyridamole (ASA–ERDP) versus clopidogrel. Methods In this double-blind, 2-by-2 factorial trial, we randomly assigned patients to receive 25 mg of aspirin plus 200 mg of extended-release dipyridamole twice daily or to receive 75 mg of clopidogrel daily. The primary outcome was first recurrence of stroke. The secondary outcome was a composite of stroke, myocardial infarction, or death from vascular causes. Sequential statistical testing of noninferiority (margin of 1.075), followed by superiority testing, was planned. Results A total of 20,332 patients were followed for a mean of 2.5 years. Recurrent stroke occurred in 916 patients (9.0%) receiving ASA–ERDP and in 898 patients (8.8%) receiving clopidogrel (hazard ratio, 1.01; 95% confidence interval [CI], 0.92 to 1.11). The secondary outcome occurred in 1333 patients (13.1%) in each group (hazard ratio for ASA–ERDP, 0.99; 95% CI, 0.92 to 1.07). There were more major hemorrhagic events among ASA–ERDP recipients (419 [4.1%]) than among clopidogrel recipients (365 [3.6%]) (hazard ratio, 1.15; 95% CI, 1.00 to 1.32), including intracranial hemorrhage (hazard ratio, 1.42; 95% CI, 1.11 to 1.83). The net risk of recurrent stroke or major hemorrhagic event was similar in the two groups (1194 ASA–ERDP recipients [11.7%], vs. 1156 clopidogrel recipients [11.4%]; hazard ratio, 1.03; 95% CI, 0.95 to 1.11). Conclusions The trial did not meet the predefined criteria for noninferiority but showed similar rates of recurrent stroke with ASA–ERDP and with clopidogrel. There is no evidence that either of the two treatments was superior to the other in the prevention of recurrent stroke. (ClinicalTrials.gov number, NCT00153062.)

Community reintegration and related factors in a Nigerian stroke sample.

Background: The goal of stroke rehabilitation has shifted from mere survival of a victim to how well a survivor can be effectively reintegrated back into the community. Objectives: The present study determined the level of satisfaction with community reintegration (CR) and related factors among Nigerian community-dwelling stroke survivors (CDSS). Methods: This was a cross-sectional survey of 71 volunteering CDSS (35 males, 36 females) from selected South-Eastern Nigerian communities. Reintegration to Normal Living Index was used to assess participants’ CR. Data was analysed using Spearman rank-order correlation, Kruskal-Wallis and Mann-Whitney U tests at p≤0.05. Results: Participants generally had deficits in CR which was either mild/moderate (52.1%) or severe (47.9%). Scores in the CR domains of distance mobility, performance of daily activities, recreational activities and family roles were particularly low (median scores ≤ 4). CR was significantly correlated with and influenced by age (r=-0.35; p=0.00) and presence/absence of diabetes mellitus (u=3.56.50; p=0.01), pre- (k=6.13; p=0.05) and post-stroke employment (k=18.26; p=0.00) status, type of assistive mobility device being used (AMD) (k=25.39; p=0.00) and support from the community (k=7.15; p=0.03) respectively. Conclusion: CR was generally poor for this CDSS sample. Survivors who are older, having diabetes as co-morbidity, using AMD (particularly wheel-chair) and without employment pre- and/or post-stroke may require keener attention. Rehabilitation focus may be targeted at enhancing mobility functions, vocational and social skills.

The relationship between baseline blood pressure and computed tomography findings in acute stroke: data from the Tinzaparin in Acute Ischaemic Stroke Trial (TAIST)

Background and Purpose—High blood pressure (BP) is present in 80% of patients with acute ischemic stroke and is independently associated with poor outcome. There are few data examining the relationship between admission BP and acute CT findings. Methods—TAIST was a randomized controlled trial assessing 10 days of treatment with tinzaparin versus aspirin in 1489 patients with acute ischemic stroke (48 hr) with admission BP of 220/120 mm Hg. CT brain scans were performed before randomization and after 10 days. The relationships between baseline BP and adjudicated CT findings were assessed. Odds ratios per 10 mm Hg change in BP were calculated. Results—Higher systolic BP (SBP) was associated with abnormal CT scans because of independent associations with chronic changes of leukoariosis (OR, 1.12; 95% CI, 1.05–1.17) and old infarction (OR, 1.12; 95% CI, 1.06 –1.17) at baseline, and signs of visible infarction at day 10 (OR, 1.06; 95% CI, 1.00 –1.13). A lower SBP was associated with signs of acute infarction (OR, 0.94; 95% CI, 0.89–0.99). Hemorrhagic transformation, dense middle cerebral artery sign, mass effect, and cerebral edema at day 10 were not independently associated with baseline BP. Conclusion—Although high baseline BP is independently associated with a poor outcome after stroke, this was not shown to be through an association with increased hemorrhagic transformation, cerebral edema, or mass effect; trial design may be suboptimal to detect this. Higher SBP is associated with visible infarction on day 10 scans. The influence of changing BP in acute stroke on CT findings is still to be ascertained.

Stroke in patients with diabetes mellitus: a study from North Western Nigeria.

Background: Stroke is one of the major causes of morbidity and mortality worldwide and apart from being exceedingly harmful in diabetics, stroke is a disabling disorder. The study was undertaken to describe the clinical characteristics, outcome pattern and predictors of mortality in a cohort of diabetic patients presenting with stroke in two tertiary health facilities in North Western Nigeria. Method: Out of all stroke patients seen from June 2007 to February 2011, persons with diabetes mellitus presenting with stroke in the emergency unit of the two tertiary hospitals in Kano were consecutively recruited for the study. Classification of stroke into hemorrhagic and infarctive subtypes was based on brain computerized tomography (CT), brain magnetic resonance imaging (MRI) and World Health Organization (WHO) criteria. Follow-up period was for thirty days. Result: Out of the five hundred and thirty six stroke patients seen during the study period, 85 (15.9%) patients, comprising 48 (56.5%) males, had diabetes. Thirty eight (44.7%) of the identified diabetics were previously undiagnosed. Sixty four (75.3%) had infarctive stroke. One-month case fatality rate was 30.6%. Factors associated with death included male sex, past history of TIA, abnormal respiratory pattern, hemorrhagic stroke, aspiration pneumonitis, and worsening GCS. Aspiration pneumonitis and worsening GCS were independent predictors of one month mortality of stroke in the patients. Conclusion: In DM patients studied, infarctive stroke was more common, case fatality was 30.6%. Male gender, past history of TIA, abnormal respiratory pattern, hemorrhagic stroke, aspiration pneumonitis, and worsening Glasgow Coma Score (GCS) were associated with mortality. Aspiration pneumonitis and worsening GCS were independent predictors of one month mortality of stroke in diabetic patients.

Interventions for dysphagia in acute stroke (Review)

Background It is unclear how dysphagic patients should be fed and treated after acute stroke. Objectives The objective of this review was to assess the effect of different management strategies for dysphagic stroke patients, in particular how and when to feed, whether to supplement nutritional intake, and how and whether to treat dysphagia. Search strategy We searched the Cochrane Stroke Group trials register, Medline, Embase, ISI, and existing review articles.We contacted researchers in the field and equipment manufacturers. Date of the most recent searches: March 1999. Selection criteria Unconfounded truly or quasi randomised controlled trials in dysphagic patients with acute/subacute (within 3 months) stroke. Data collection and analysis Three reviewers independently applied the trial inclusion criteria. Two reviewers assessed trial quality and extracted the data. Main results Percutaneous endoscopic gastrostomy (PEG) versus nasogastric tube (NGT) feeding: two trials (49 patients) suggest that PEG reduces end-of-trial case fatality (Peto Odds Ratio, OR 0.28, 95% CI 0.09 to 0.89) and treatment failures (OR 0.10, 95% CI 0.02 to 0.52), and improves nutritional status, assessed as weight (Weighted Men Difference, WMD +4.1 kg, 95% CI -4.3 to +12.5), mid-arm circumference (WMD +2.2 cm, 95% CI -0.5 to +4.9) or serum albumin (WMD + 7.0 g/l, 95% CI +4.9 to +9.1) as compared with NGT feeding; two larger studies are ongoing. Timing of feeding: no completed trials; one large study is ongoing. Swallowing therapy for dysphagia: two trials (85 patients) suggest that formal swallowing therapy does not significantly reduce end-of-trial dysphagia rates (OR 0.55, 95%CI 0.18 to 1.66). Drug therapy for dysphagia: one trial (17 patients); nifedipine did not alter end-of-trial case fatality or the frequency of dysphagia. Nutritional supplementation: one trial (42 patients) found a non-significant trend to a lower case fatality, and significantly increased energy and protein intake; one large trial is ongoing and data is awaited from two other studies. Fluid supplementation: one trial (20 patients) found that supplementation did not alter the time to resolution of dysphagia. Authors’ conclusions Too few studies have been performed, and these have involved too few patients. PEG feeding may improve outcome and nutrition as compared with NGT feeding. Further research is required to assess how and when patients are fed, and the effect of swallowing or drug therapy on dysphagia.

Dipyridamole plus aspirin versus aspirin alone in the secondary prevention after TIA or stroke: a meta-analysis by risk

Objectives: Our aim was to study the effect of combination therapy with aspirin and dipyridamole (A+D) over aspirin alone (ASA) in secondary prevention after transient ischemic attack or minor stroke of presumed arterial origin and to perform subgroup analyses to identify patients that might benefit most from secondary prevention with A+D. Data sources: The previously published meta-analysis of individual patient data was updated with data from ESPRIT (N=2,739); trials without data on the comparison of A+D versus ASA were excluded. Review methods: A meta-analysis was performed using Cox regression, including several subgroup analyses and following baseline risk stratification. Results: A total of 7,612 patients (5 trials) were included in the analyses, 3,800 allocated to A+D and 3,812 to ASA alone. The trial-adjusted hazard ratio for the composite event of vascular death, non-fatal myocardial infarction and non-fatal stroke was 0.82 (95% confidence interval 0.72-0.92). Hazard ratios did not differ in subgroup analyses based on age, sex, qualifying event, hypertension, diabetes, previous stroke, ischemic heart disease, aspirin dose, type of vessel disease and dipyridamole formulation, nor across baseline risk strata as assessed with two different risk scores. A+D were also more effective than ASA alone in preventing recurrent stroke, HR 0.78 (95% CI 0.68 – 0.90). Conclusion: The combination of aspirin and dipyridamole is more effective than aspirin alone in patients with TIA or ischemic stroke of presumed arterial origin in the secondary prevention of stroke and other vascular events. This superiority was found in all subgroups and was independent of baseline risk. ---------------------------7dc3521430776 Content-Disposition: form-data; name="c14_creators_1_name_family" Halkes

Can we improve the statistical analysis of stroke trials? Statistical reanalysis of functional outcomes in stroke trials

Background and Purpose—Most large acute stroke trials have been neutral. Functional outcome is usually analyzed using a yes or no answer, eg, death or dependency versus independence. We assessed which statistical approaches are most efficient in analyzing outcomes from stroke trials. Methods—Individual patient data from acute, rehabilitation and stroke unit trials studying the effects of interventions which alter functional outcome were assessed. Outcomes included modified Rankin Scale, Barthel Index, and “3 questions”. Data were analyzed using a variety of approaches which compare 2 treatment groups. The results for each statistical test for each trial were then compared. Results—Data from 55 datasets were obtained (47 trials, 54 173 patients). The test results differed substantially so that approaches which use the ordered nature of functional outcome data (ordinal logistic regression, t test, robust ranks test, bootstrapping the difference in mean rank) were more efficient statistically than those which collapse the data into 2 groups (2; ANOVA, P0.001). The findings were consistent across different types and sizes of trial and for the different measures of functional outcome. Conclusions—When analyzing functional outcome from stroke trials, statistical tests which use the original ordered data are more efficient and more likely to yield reliable results. Suitable approaches included ordinal logistic regression, test, and robust ranks test.

Relationship between hyperacute blood pressure and outcome after ischemic stroke: data from the VISTA Collaboration

Background and Purpose—High blood pressure (BP) is associated independently with poor outcome after acute ischemic stroke, although in most analyses “baseline” BP was measured 24 hours or more postictus, and not during the hyperacute period. Methods—Analyses included 1722 patients in hyperacute trials (recruitment 8 hours) from the Virtual Stroke International Stroke Trial Archive (VISTA) Collaboration. Data on BP at enrolment and after 1, 2, 16, 24, 48, and 72 hours, neurological impairment at 7 days (NIHSS), and functional outcome at 90 days (modified Rankin scale) were assessed using logistic regression models, adjusted for confounding variables; results are for 10-mm Hg change in BP. Results—Mean time to enrolment was 3.7 hours (range 1.0 to 7.9). High systolic BP (SBP) was significantly associated with increased neurological impairment (odds ratio, OR 1.06, 95% confidence interval, 95% CI 1.01 to 1.12), and poor functional outcome; odds ratios for both increased with later BP measurements made at up to 24 hours poststroke. Smaller (versus larger) declines in SBP over the first 24 hours were significantly associated with poor NIHSS scores (OR 1.16, 95% CI 1.05 to 1.27) and functional outcome (OR 1.23, 95% CI 1.13 to 1.34). A large variability in SBP was also associated with poor functional outcome. Conclusions—High SBP and large variability in SBP in the hyperacute stages of ischemic stroke are associated with increased neurological impairment and poor functional outcome, as are small falls in SBP over the first 24 hours.

Stem cells for enhancing recovery after stroke: a review

The potential application for stem cell therapy is vast, and development for use in ischaemic stroke is still in its infancy. Access to stem cells for research is contentious; however, stem cells are obtainable from both animal and human. Despite a limited understanding of their mechanisms of action, clinical trials assessing stem cells in human stroke have been performed. Trials are also underway evaluating haematopoietic precursors mobilised with granulocyte-colony stimulating factor, an approach offering an autologous means of administrating stem cells for therapeutic purposes. This review summarises current knowledge in regard to stem cells and their potential for helping improve recovery after stroke.

Speeding stroke recovery? A systematic review of amphetamine after stroke

Introduction: The use of drugs to enhance recovery (“rehabilitation pharmacology”) has been assessed. Amphetamine can improve outcome in experimental models of stroke, and several small clinical trials have assessed its use in stroke. Methods: Electronic searches were performed to identify randomised controlled trials of amphetamine in stroke (ischaemic or haemorrhagic). Outcomes included functional outcome (assessed as combined death or disability/dependency), safety (death) and haemodynamic measures. Data were analysed as dichotomous or continuous outcomes, using odds ratios (OR), weighted or standardised mean difference, (WMD or SMD) using random-effects models with 95% confidence intervals (95% CI); statistical heterogeneity was assessed. Results: Eleven completed trials (n=329) were identified. Treatment with amphetamine was associated with non-significant trends to increased death (OR 2.78 (95% CI, 0.75– 10.23), n=329, 11 trials) and improved motor scores (WMD 3.28 (95% CI −0.48–7.04) n=257, 9 trials) but had no effect on the combined outcome of death and dependency (OR 1.15 (95% CI 0.65–2.06, n=206, 5 trials). Amphetamine increased systolic blood pressure (WMD 9.3 mmHg, 95% CI 3.3–15.3, n=106, 3 trials) and heart rate (WMD 7.6 beats per minute (bpm), 95% CI 1.8–13.4, n=106, 3 trials). Despite variations in treatment regimes, outcomes and follow-up duration there was no evidence of significant heterogeneity or publication bias. Conclusion: No evidence exists at present to support the use of amphetamine after stroke. Despite a trend to improved motor function, doubts remain over

Granulocyte-colony stimulating factor in experimental stroke and its effects on infarct size and functional outcome: a systematic review

Background Granulocyte-colony stimulating factor (G-CSF) shows promise as a treatment for stroke. This systematic review assesses G-CSF in experimental ischaemic stroke. Methods Relevant studies were identified with searches of Medline, Embase and PubMed. Data were extracted on stroke lesion size, neurological outcome and quality, and analysed using Cochrane Review Manager using random effects models; results are expressed as standardised mean difference (SMD) and odds ratio (OR). Results Data were included from 19 publications incorporating 666 animals. G-CSF reduced lesion size significantly in transient (SMD -1.63, p<0.00001) but not permanent (SMD -1.56, p=0.11) focal models of ischaemia. Lesion size was reduced at all doses and with treatment commenced within 4 hours of transient ischaemia. Neurological deficit (SMD -1.37, p=0.0004) and limb placement (SMD -1.88, p=0.003) improved with G-CSF; however, locomotor activity (>4 weeks post ischaemia) was not (SMD 0.76, p=0.35). Death (OR 0.27, p<0.0001) was reduced with G-CSF. Median study quality was 4 (range 0-7/8); Egger’s test suggested significant publication bias (p=0.001). Conclusions G-CSF significantly reduced lesion size in transient but not permanent models of ischaemic stroke. Motor impairment and death were also reduced. Further studies assessing dose-response, administration time, length of ischaemia and long-term functional recovery are needed.

Quality of life after first-ever stroke: An interviewbased study from Blantyre, Malawi

Background In post-stroke patients, impairment of quality of life (QOL) has been associated with functional impairment, age, anxiety, depression, and fatigue. Good social support, higher education, and better socioeconomic status are associated with better QOL among stroke survivors. In Africa, studies from Nigeria and Tanzania have reported on post-stroke QOL. Aim The aim of this study was to describe QOL more than six months after first-ever stroke in Malawi. Methods This was an interview-based study about a stroke-surviving cohort. Adult patients were interviewed six or twelve months after their first ever stroke. HIV status, modified stroke severity scale (mNIHSS) score, and brain scan results were recorded during the acute phase of stroke. At the time of the interviews, the modified Rankin scale (mRS) was used to assess functional outcome. The interviews applied the Newcastle Stroke-specific Quality of Life Measure (NEWSQOL). All the data were analysed using Statview™: the X2 test compared proportions, Student’s t-test compared means for normally distributed data, and the Kruskal-Wallis test was used for nonparametric data. Results Eighty-one patients were followed up at least six months after the acute stroke. Twenty-five stroke patients (ten women) were interviewed with the NEWSQOL questionnaire. Good functional outcome (lower mRS score) was positively associated with better QOL in the domains of activities of daily living (ADL)/self-care (p = 0.0024) and communication (p = 0.031). Women scored worse in the fatigue (p = 0.0081) and cognition (p = 0.048) domains. Older age was associated with worse QOL in the ADL (p = 0.0122) domain. Seven patients were HIV-seroreactive. HIV infection did not affect post-stroke QOL. Conclusion In Malawi, within specific domains, QOL after stroke appeared to be related to patients’ age, sex, and functional recovery in this small sample of patients.