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

Should data monitoring committees assess efficacy when considering safety in trails in acute stroke?

The primary role of a trials Data Monitoring Committee (DMC) is to ensure the safety of enrolled patients. In stroke trials, safety is monitored typically by comparing death and stroke specific events between treatment groups. DMCs may also have the remit for monitoring efficacy depending on the aims of the trial. We hypothesised that functional outcome at end of follow-up, a measure of efficacy, is also a powerful measure of safety and tested this in a systematic review

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.

Relationship between therapeutic changes in blood pressure and outcomes in acute stroke: a metaregression

Both low and high blood pressure (BP) during the acute phase of stroke are associated independently with a poor outcome. Several small clinical trials have involved the alteration of BP and this study assessed the relationship between change in BP and functional outcome. Randomised controlled trials of interventions that would be expected, on pharmacological grounds, to alter BP in patients within one week of the onset of acute ischaemic or haemorrhagic stroke were sought using electronic searches. Data were collected on BP and clinical outcome. The relationship between the difference in on-treatment BP and odds ratios (OR) for outcomes was assessed using meta-regression. Thirty-seven trials involving 9,008 patients were included. A ‘U’ or ‘J’ shaped relationship were found between on-treatment BP difference and early death, death at the end of 90 day follow up, and combined death or dependency at the end of follow up. Although outcomes were not significantly reduced at any level of change in BP, the lowest odds occurred at: early death (OR 0.87, 95% confidence interval, CI 0.54 to 1.23) - 8.1 mmHg; death at end of follow up (OR 0.96, 95% CI 0.31 to 1.65) - 14.4 mmHg; and combined death or dependency at end of follow up (OR 0.95, 95% CI 0.11 to 1.72) - 14.6 mmHg. Although large falls or increases in BP are associated with a worse outcome, modest reductions may reduce death, and combined death or dependency, although the confidence intervals are wide and compatible with overall benefit or hazard.

The Virtual International Stroke Trials Archive

Background and Purpose - Stroke has global importance and it causes an increasing amount of human suffering and economic burden, but its management is far from optimal. The unsuccessful outcome of several research programs highlights the need for reliable data on which to plan future clinical trials. The Virtual International Stroke Trials Archive aims to aid the planning of clinical trials by collating and providing access to a rich resource of patient data to perform exploratory analyses. Methods - Data were contributed by the principal investigators of numerous trials from the past 16 years. These data have been centrally collated and are available for anonymized analysis and hypothesis testing. Results - ”Currently, the Virtual International Stroke Trials Archive contains 21 trials. There are data on 15 000 patients with both ischemic and hemorrhagic stroke. Ages range between 18 and 103 years, with a mean age of 6912 years. Outcome measures include the Barthel Index, Scandinavian Stroke Scale, National Institutes of Health Stroke Scale, Orgogozo Scale, and modified Rankin Scale. Medical history and onset-to-treatment time are readily available, and computed tomography lesion data are available for selected trials. Conclusions - This resource has the potential to influence clinical trial design and implementation through data analyses that inform planning. (Stroke. 2007;38:1905-1910.)

Calculation of sample size for stroke trials assessing functional outcome: comparison of binary and ordinal approaches

Background Many acute stroke trials have given neutral results. Sub-optimal statistical analyses may be failing to detect efficacy. Methods which take account of the ordinal nature of functional outcome data are more efficient. We compare sample size calculations for dichotomous and ordinal outcomes for use in stroke trials. Methods Data from stroke trials studying the effects of interventions known to positively or negatively alter functional outcome – Rankin Scale and Barthel Index – were assessed. Sample size was calculated using comparisons of proportions, means, medians (according to Payne), and ordinal data (according to Whitehead). The sample sizes gained from each method were compared using Friedman 2 way ANOVA. Results Fifty-five comparisons (54 173 patients) of active vs. control treatment were assessed. Estimated sample sizes differed significantly depending on the method of calculation (Po00001). The ordering of the methods showed that the ordinal method of Whitehead and comparison of means produced significantly lower sample sizes than the other methods. The ordinal data method on average reduced sample size by 28% (inter-quartile range 14–53%) compared with the comparison of proportions; however, a 22% increase in sample size was seen with the ordinal method for trials assessing thrombolysis. The comparison of medians method of Payne gave the largest sample sizes. Conclusions Choosing an ordinal rather than binary method of analysis allows most trials to be, on average, smaller by approximately 28% for a given statistical power. Smaller trial sample sizes may help by reducing time to completion, complexity, and financial expense. However, ordinal methods may not be optimal for interventions which both improve functional outcome

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

Background: Most large acute stroke trials have been neutral. Functional outcome is usually analysed using a yes or no answer, e.g. death or dependency vs. independence. We assessed which statistical approaches are most efficient in analysing 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 analysed using a variety of approaches which compare two 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 (chi square) (ANOVA p<0.001). The findings were consistent across different types and sizes of trial and for the different measures of functional outcome. Conclusions: When analysing 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, t-test, and robust ranks test.

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.