BACKGROUND: Most ischaemic strokes are caused by blood clots blocking an artery in the brain. Clot prevention with anticoagulant therapy could have a significant impact on patient survival, disability and recurrence of stroke. OBJECTIVES: The objective of this review was to assess the effect of anticoagulant therapy in the early treatment of patients with acute ischaemic stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register (most recent search: March 1999) and consulted MedStrategy (1995). We also contacted drug companies. SELECTION CRITERIA: Randomised trials comparing early anticoagulant therapy (started within two weeks of stroke onset) with control in patients with acute presumed or confirmed ischaemic stroke. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion, assessed trial quality and extracted the data. MAIN RESULTS: Twenty-one trials involving 23,427 patients were included. The quality of the trials varied considerably. The anticoagulants tested were standard unfractionated heparin, low-molecular-weight heparins, heparinoids, oral anticoagulants, and thrombin inhibitors. Based on eight trials (22,450 patients) there was no evidence that anticoagulant therapy reduced the odds of death from all causes (odds ratio 1.05, 95% confidence intervals 0.98-1.12). Similarly, based on five trials (21, 846 patients), there was no evidence that anticoagulants reduced the odds of being dead or dependent at the end of follow-up (odds ratio 0.99, 95% confidence intervals 0.94-1.05). Although anticoagulant therapy was associated with about 9 fewer recurrent ischaemic strokes per 1000 patients treated, it was also associated with a similar sized 9 per 1000 increase in symptomatic intracranial haemorrhages. Similarly, anticoagulants avoided about 4 pulmonary emboli per 1000, but this benefit was offset by an extra 9 major extracranial haemorrhages per 1000. Sensitivity analyses did not identify a particular type of anticoagulant regimen or patient characteristic associated with net benefit. REVIEWER'S CONCLUSIONS: Immediate anticoagulant therapy in patients with acute ischaemic stroke is not associated with net short- or long-term benefit. The data from this review do not support the routine use of any type of anticoagulant in acute ischaemic stroke.

Anticoagulants↗

PubMed2000

Antiplatelet therapy for acute ischaemic stroke.

BACKGROUND: In patients with acute ischaemic stroke, platelets become activated. Antiplatelet therapy might reduce the volume of brain damaged by ischaemia and reduce the risk of early recurrent ischaemic stroke. This might reduce the risk of early death and improve long-term outcome in survivors. However, antiplatelet therapy might also increase the risk of fatal or disabling intracranial haemorrhage. OBJECTIVES: The aim of this review is to assess the net result of antiplatelet therapy in acute ischaemic stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register (most recent date of search March 1999), the register of trials held by the Antiplatelet Trialists' Collaboration, and MedStrategy (1995). We also contacted relevant pharmaceutical companies. SELECTION CRITERIA: Randomised trials comparing antiplatelet therapy started within 14 days of the stroke with control in patients with definite or presumed ischaemic stroke. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied the inclusion criteria and assessed trial quality, and for the included trials, extracted and cross-checked the data. MAIN RESULTS: Eight trials involving 41,325 patients were included. Two trials testing aspirin 160 to 300 mg once daily started within 48 hours of onset contributed 98% of the data. The maximum follow-up was six months. With treatment, there was a significant decrease in death or dependency at the end of follow-up (OR = 0.94; 95% CI 0.91 - 0.98). In absolute terms, 13 more patients were alive and independent at the end of follow-up for every 1000 patients treated. Furthermore, treatment increased the odds of making a complete recovery from the stroke (OR = 1.06; 95% CI 1.01 - 1.11). In absolute terms, 10 patients made a complete recovery for every 1000 patients treated. Antiplatelet therapy was associated with a small but definite excess of 2 symptomatic intracranial haemorrhages for every 1000 patients treated, but this was more than offset by a reduction of 7 recurrent ischaemic strokes for every 1000 patients treated. REVIEWER'S CONCLUSIONS: Antiplatelet therapy with aspirin 160 to 300 mg daily, given orally (or per rectum in patients who cannot swallow), and started within 48 hours of onset of presumed ischaemic stroke reduces the risk of early recurrent ischaemic stroke without a major risk of early haemorrhagic complications and improves long-term outcome.

Brain Ischemia↗

PubMed2000

Low-molecular-weight heparins or heparinoids versus standard unfractionated heparin for acute ischaemic stroke.

BACKGROUND: Low molecular weight heparins and heparinoids may be associated with lower risks of haemorrhage and more powerful antithrombotic effects than standard unfractionated heparin. OBJECTIVES: The objective of this review was to compare the effects of low molecular weight heparins or heparinoids with those of unfractionated heparin in people with acute confirmed or presumed ischaemic stroke. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register and MedStrategy (1995). We also contacted pharmaceutical companies. Date of most recent search: April 1999. SELECTION CRITERIA: Randomised trials comparing heparinoids or low molecular weight heparins with standard unfractionated heparin in people with acute ischaemic stroke. Only trials where treatment was started within 14 days of stroke onset were included. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected studies for inclusion, assessed trial quality and extracted the data. MAIN RESULTS: Five trials involving 705 people were included. Four trials compared a heparinoid (danaparoid), and one compared a low molecular weight heparin (enoxaparin), with standard unfractionated heparin. Overall, 55/414 (13%) of the patients allocated danaparoid or enoxaparin had deep vein thrombosis compared with 65/291 (22%) of those allocated unfractionated heparin. This reduction was significant (odds ratio 0.52, 95% confidence interval 0.56 - 0.79). However, the number of more major events (pulmonary embolism, death, intra-cranial or extra-cranial haemorrhage) was too small to provide a reliable estimate of more important benefits and risks. No information was reported for recurrent stroke or functional outcome in survivors. REVIEWER'S CONCLUSIONS: Low molecular weight heparin or heparinoid appear to decrease the occurrence of deep vein thrombosis compared to standard unfractionated heparin, but there are too few data to provide reliable information on their effect on other important outcomes, including death and intracranial haemorrhage.

Anticoagulants↗

PubMed2000

Anticoagulants for preventing recurrence following ischaemic stroke or transient ischaemic attack.

BACKGROUND: After a first stroke, further vascular events (especially myocardial infarction and recurrent stroke) are common and often fatal. OBJECTIVES: The objective of this review was to assess the effect of prolonged anticoagulant therapy following presumed non-embolic ischaemic stroke or transient ischaemic attack. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register. We contacted companies marketing anticoagulant agents. SELECTION CRITERIA: Randomised and quasi-randomised trials comparing anticoagulant therapy, for at least one month, with control in people with previous non-embolic presumed ischaemic stroke or transient ischaemic attack. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion, assessed trial quality and extracted the data. MAIN RESULTS: Nine trials involving 1214 patients were included. The quality of all trials was poor. All pre-dated routine computerised tomography scanning and use of the International Normalised Ratio to monitor anticoagulation. Anticoagulant therapy did not significantly reduce the odds of death or dependency (two trials, odds ratio 0.83, 95% confidence interval 0.52 to 1.34). Death from any cause (odds ratio 0.95, 95% confidence interval 0.72 to 1.23), and death from vascular causes (odds ratio 0.86, 95% confidence interval 0.66 to 1.13) were not significantly different between treatment and control across all nine trials. Anticoagulant therapy did not reduce the risk of recurrent stroke (odds ratio 0.79, 95% confidence interval 0.56 to 1.13). However, fatal intracranial haemorrhage increased (odds ratio 2.54, 95% confidence interval 1.19 to 5.45), as did major extracranial haemorrhage (odds ratio 4.87, 95% confidence interval 2.50 to 9.49). This means anticoagulant therapy caused 11 additional fatal intracranial haemorrhages and 25 additional major extracranial haemorrhages per year for every 1000 patients given anticoagulant therapy. REVIEWER'S CONCLUSIONS: There appears to be no clear benefit from long-term anticoagulant therapy in people with non-embolic presumed ischaemic stroke or transient ischaemic attack. There appears to be a significant bleeding risk associated with anticoagulant therapy.

Anticoagulants↗

PubMed2000

Snapshot view of emergency neurolosurgical head injury care.

Explore the source record for details and available documents.

Adrenal Cortex Hormones↗

PubMed2000

Are the modified "simple questions" a valid and reliable measure of health related quality of life after stroke? United Kingdom Collaborators in the International Stroke Trial.

OBJECTIVES: Two "simple questions" were developed as a minimalist measurement tool to assess outcome in large trials and epidemiological studies after stroke. A previous study of their validity had disclosed ambiguities in their wording. In this study, the clarity, validity, and reliability of a modified version of these simple questions were examined. The relation between patients' responses to these questions and two widely used generic measures of health related quality of life were also studied. METHODS: A hospital based stroke register cohort of 152 patients, who were all visited at home by a study nurse, was used to study validity. A cohort of 1753 patients derived from the International Stroke Trial was used to study the relation with measures of quality of life. The sensitivity, specificity, and accuracy with which responses to each question predicted the patients' outcome measured using standard instruments was assessed. The distribution of scores for the EuroQol and SF-36 was examined for patients classified as dependent, independent, and fully recovered by the combined use of the modified simple questions. RESULTS: The modified "dependency" question had excellent sensitivity (>85%), specificity (>79%), and accuracy (>82%) for identifying dependency after stroke. The "problems" question had good sensitivity (65-88%) and moderate specificity (36-72%) for the detection of problems in a broad range of domains. The combined use of the modified dependency and problems questions provided a valid, simple, and reliable overall indicator of health related quality of life after stroke. CONCLUSIONS: The modified simple questions have excellent face validity and good measurement properties for the assessment of outcome after stroke. They are particularly well suited for large epidemiological studies and randomised trials.

Humans↗

PubMed2000

Indications for early aspirin use in acute ischemic stroke : A combined analysis of 40 000 randomized patients from the chinese acute stroke trial and the international stroke trial. On behalf of the CAST and IST collaborative groups.

BACKGROUND AND PURPOSE: Long-term daily aspirin is of benefit in the years after ischemic stroke, and 2 large randomized trials (the Chinese Acute Stroke Trial [CAST] and the International Stroke Trial [IST]), with 20 000 patients in each, have shown that starting daily aspirin promptly in patients with suspected acute ischemic stroke also reduces the immediate risk of further stroke or death in hospital and the overall risk of death or dependency. However, some uncertainty remains about the effects of early aspirin in particular categories of patient with acute stroke. METHODS: To assess the balance of benefits and risks of aspirin in particular categories of patient with acute stroke (eg, the elderly, those without a CT scan, or those with atrial fibrillation), a prospectively planned meta-analysis is presented of the data from 40 000 individual patients from both trials on events that occurred in the hospital during the scheduled treatment period (4 weeks in CAST, 2 weeks in IST), with 10 characteristics used to define 28 subgroups. This represents 99% of the worldwide evidence from randomized trials. RESULTS: There was a highly significant reduction of 7 per 1000 (SD 1) in recurrent ischemic stroke (320 [1.6%] aspirin versus 457 [2. 3%] control, 2P<0.000001) and a less clearly significant reduction of 4 (SD 2) per 1000 in death without further stroke (5.0% versus 5. 4%, 2P=0.05). Against these benefits, there was an increase of 2 (SD 1) per 1000 in hemorrhagic stroke or hemorrhagic transformation of the original infarct (1.0% versus 0.8%, 2P=0.07) and no apparent effect on further stroke of unknown cause (0.9% versus 0.9%). In total, therefore, there was a net decrease of 9 (SD 3) per 1000 in the overall risk of further stroke or death in hospital (8.2% versus 9.1%, 2P=0.001). For the reduction of one third in recurrent ischemic stroke, subgroup-specific analyses found no significant heterogeneity of the proportional benefit of aspirin (chi(2)(18)=20. 9, NS), even though the overall treatment effect (chi(2)(1)=24.8, 2P<0.000001) was sufficiently large for such subgroup analyses to be statistically informative. The absolute risk among control patients was similar in all 28 subgroups, so the absolute reduction of approximately 7 per 1000 in recurrent ischemic stroke does not differ substantially with respect to age, sex, level of consciousness, atrial fibrillation, CT findings, blood pressure, stroke subtype, or concomitant heparin use. There was no good evidence that the apparent decrease of approximately 4 per 1000 in death without further stroke was reversed in any subgroup or that in any subgroup the increase in hemorrhagic stroke was much larger than the overall average of approximately 2 per 1000. Finally, there was no significant heterogeneity between the reductions in the composite outcome of any further stroke or death (chi(2)(18)=16.5, NS). Among the 9000 patients (22%) randomized without a prior CT scan, aspirin appeared to be of net benefit with no unusual excess of hemorrhagic stroke; moreover, even among the 800 (2%) who had inadvertently been randomized after a hemorrhagic stroke, there was no evidence of net hazard (further stroke or death, 63 aspirin versus 67 control). CONCLUSIONS: Early aspirin is of benefit for a wide range of patients, and its prompt use should be routinely considered for all patients with suspected acute ischemic stroke, mainly to reduce the risk of early recurrence.

Acute Disease↗

PubMed1999

[International Stroke Trial Switzerland: some epidemiologic data].

Randomised trials provide the best evidence on the effects of treatment on a particular disease. They can also provide valuable data on outcome. In the present article, data from 1631 Swiss patients randomised in the International Stroke Trial (IST) are presented. Baseline characteristics and outcome in the Swiss patients were compared with the 17,804 patients randomised in other countries. On average, compared with other countries, Swiss patients were: 2.5 years older (CI: 1.9-3.1; p < 0.001); more likely to have presented with total anterior circulation infarcts (28 vs 23%); less likely to have lacunar strokes (16 vs 25%; p < 0.00001); more likely to be randomised and treated early (within 3 hours, 7 vs 4%, and within 6 hours, 25 vs 15%; p < 0.00001). However, Swiss patients were more likely to be dead or dependent 6 months after the stroke (66.9 vs 62.2%; p < 0.00001). The difference in death or dependency was almost entirely explained by the difference in age and baseline severity of strokes. These data highlight the difficulties inherent in between-country comparisons of outcome after stroke. They also emphasise the need for international multicentre trials to use methods of randomisation (either stratification or minimisation), as IST did, to ensure balance of prognostic factors within each participating country; to do otherwise might confound the assessment of the effect of treatment.

Aged↗

PubMed1999

Research funding.

Explore the source record for details and available documents.

Biomedical Research↗

PubMed1999

Is there still a role for intravenous heparin in acute stroke? No.

Explore the source record for details and available documents.

Acute Disease↗

PubMed1999

Corticosteroids in head injury--the CRASH trial.

Explore the source record for details and available documents.

Adrenal Cortex Hormones↗

PubMed1999

Reports of randomized trials in acute stroke, 1955 to 1995. What proportions were commercially sponsored?

BACKGROUND AND PURPOSE: Research in acute stroke has expanded rapidly. Many potentially important interventions lack commercial potential (eg, admission to a stroke unit). We therefore wished to examine the frequency of reports of randomized trials of interventions for acute stroke over the past 40 years, the source of support for such trials, the reporting of the commercial involvement, and whether the proportion of commercially supported trials had changed. METHODS: Eligible trials were identified from the Cochrane Stroke Group's specialized register of controlled clinical trials. We included all randomized trials in patients with acute stroke which published a full text report, in English, between 1955 and 1995. Two reviewers independently extracted data on the involvement of the pharmaceutical industry in all eligible trials. RESULTS: There was a substantial increase in the number of acute stroke trials published per year between 1955 and 1995. The description of pharmaceutical industry involvement in each trial report was poor. Only a minority of supported trials made explicit statements about the role of the sponsoring company. The proportion of trials apparently supported by the pharmaceutical industry has increased substantially. CONCLUSIONS: The increasingly important role of the pharmaceutical industry in evaluating new treatments gives substantial scope for bias and may not be in the interests of public health. Poor reporting of the sponsor's involvement suggests that modifications to the guidelines for the reporting of randomized controlled trials to include more details of the sponsor's involvement in the design, conduct, management, analysis, and reporting of the trial are justified.

Acute Disease↗