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Query: UMLS:C0038454 (stroke)
 147,016 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The rationale for the Multicenter Acute Stroke Trial (MAST) is presented in a companion article appearing in this issue. Acute ischaemic stroke is the third major cause of death in developed countries, and a major cause of disability. Despite a very poor prognosis, no treatment has demonstrated an efficacy in lowering the mortality and disability resulting from stroke events. Thrombolysis has been proven to reduce mortality in myocardial infarction, and it has been shown able to induce recanalisation when administered to acute stroke patients. A recent meta analysis of small-sized studies suggests that thrombolysis could offer some benefit to stroke patients, by reducing the mortality and severe invalidity by 56%; these results need to be confirmed in adequately designed and sized studies.
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PMID:Protocol for the Multicenter Acute Stroke Trial--thrombolysis study. 1017 65

Stroke is an important health problem in developed countries, being a common cause of death and disability. Prognosis is poor for hospitalised stroke patients, with a 30-day mortality rate of 20-30%, and 30% of the survivors remaining severely disabled. Based on results from experimental animal studies it is thought that early intervention will improve the patients' prognosis. Thrombolytic therapy has been shown to reduce mortality in patients with acute myocardial infarction, and several trials aim to assess its efficacy in patients with acute cerebral infarction. Although many clinical trials have been performed to address this problem, none have provided a clear answer, either because the sample size was insufficient, or by modern standards, the methodology used was not adequate. The Multicenter Acute Stroke Trials (MAST) has been designed to assess the safety and efficacy of thrombolytic therapy with streptokinase for this indication.
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PMID:Rationale for testing thrombolysis in acute ischaemic stroke. MAST Group. 1017 66

The neuroprotective properties of the nootropic agent piracetam together with reported hemorrheologic and antithrombotic effects provided the rationale for the evaluation of piracetam in acute stroke. Pilot studies showed an increase in compromised regional cerebral blood flow and improvement in motor function, aphasia and level of consciousness. Subsequently the Piracetam in Acute Stroke Study (PASS) was performed and the chief results have recently been reported (Stroke 28 (1997) 2347-2352). This was a multicenter double-blind trial in 927 patients to determine whether, compared with placebo, piracetam improved outcome when given within 12 hours of the onset of acute ischemic stroke, confirmed by computed tomography within 24 hours of admission (but not necessarily prior to treatment). Patients received an initial iv bolus of placebo or 12g piracetam, 12g piracetam daily for 4 weeks and maintenance treatment for a further 8 weeks. Neurologic status at 4 weeks was the primary end point; secondary outcome measures were functional outcome and aphasia at 12 weeks. Results in aphasic patients have not previously been reported. Analysis was planned both in all patients (n = 927) and an early treatment subgroup (n = 460) treated within 6 hours of stroke onset. This period was subsequently redefined as 7 hours. Intention-to-treat analyses in the total population showed a significant (P = 0.04) increase compared with placebo in the number of patients recovered from aphasia but no significant neurologic or functional improvement. Post hoc analysis in the early treatment subgroup showed improved neurologic outcome (P = 0.07), better function (P = 0.02) and a greater recovery rate from aphasia (P = 0.02). Additional analysis in this early treatment subgroup confined to 360 patients with moderate and severe stroke showed significant improvement in all 3 outcomes. There was no significant difference in mortality between treatment groups after 12 weeks. There were fewer deaths in piracetam-treated patients in those patients in the intention-to-treat population admitted with primary hemorrhagic stroke.
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PMID:Piracetam in the treatment of acute stroke. 1033 5

Recent post-marketing surveillance reports have confirmed the benign safety profile and lack of organ toxicity shown by piracetam during its 25 years of clinical usage. Tolerance has proved equally good with the more recent use of larger doses (up to 24 g/day) for the long-term control of cortical myoclonus and when given intravenously to patients with acute stroke. This paper provides a brief review of these findings and records the safety of piracetam as found in the Piracetam in Acute Stroke Study (PASS), a randomized multicenter placebo-controlled study in 927 patients with acute ischemic stroke. Patients receive one intravenous bolus injection of placebo or 12 g piracetam, piracetam 12 g daily for 4 weeks and maintenance treatment for 8 weeks. The major results have been reported (De Deyn et al., Stroke 28 [1997] 2347-2352). Safety was assessed taking into account adverse events including abnormal laboratory test results and mortality. Death within 12 weeks occurred more frequently in the piracetam group but the difference from placebo was not significant. Of many potential risk, prognostic and treatment-related factors examined by logistic regression, 6 contributed significantly to death of which the most important were initial severity of stroke and age. Neither treatment nor any treatment-related factor contributed significantly to death. Adverse events were similar in frequency, type and severity in piracetam and placebo groups. Events of cerebral, non-cerebral and uncertain origin likewise occurred with similar frequency. Few patients discontinued because of adverse events. There was no difference between treatments in the frequency of events associated with bleeding, including hemorrhagic transformation of infarction. An important finding was that, of 31 patients with primary hemorrhagic stroke enrolled, 3 piracetam-treated patients died compared with 6 on placebo. The results suggest that piracetam in high dosage may be given to patients with acute stroke without significant adverse effects.
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PMID:The clinical safety of high-dose piracetam--its use in the treatment of acute stroke. 1033 6

Piracetam has been shown to improve speech in aphasic patients. This paper reviews the evidence for this benefit in aphasic patients with acute stroke and, in conjunction with language treatment, in post-acute and chronic aphasia. Early double-blind, placebo-controlled trials in acute stroke showed improvement in several neurologic parameters including aphasia. Subsequently two randomized double-blind placebo-controlled studies were performed which utilised the Aachen Aphasia Test (AAT), a validated and standardized procedure, to assess language function. Patients received placebo or piracetam 4.8g daily for 12 weeks in one study and for 6 weeks in the other. In both studies patients received concomitant intensive speech therapy; one included patients 6-9 weeks after stroke while in the other the duration of aphasia varied between 4 weeks and 3 years. Compared with placebo there was improvement in both studies on piracetam in all 5 subtests of the AAT and significant overall improvement in aphasia. This indicated that, given in conjunction with language therapy, piracetam improved speech in patients with post-acute and chronic aphasia. In the Piracetam in Acute Stroke Study (PASS), of 927 patients treated within 12 hours of the onset of acute ischemic stroke, 373 were aphasic. Treatment consisted of placebo or an intravenous bolus of 12g piracetam, 12g piracetam daily for 4 weeks and 4.8 g daily for a further 8 weeks. After 12 weeks significantly more patients (approximately 10%, P=0.04) had recovered from aphasia on piracetam than placebo while in 197 patients treated within 7 hours of stroke onset, the difference in favor of piracetam was 16% (P= 0.02). These studies indicate that piracetam improves aphasia in acute stroke and, as an adjuvant to language therapy, in post-acute and chronic aphasia.
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PMID:The role of piracetam in the treatment of acute and chronic aphasia. 1033 7

The pathophysiology of ischemic neuronal cell damage has been studied extensively. Intracellular calcium ions, excitatory amino acids, nitric oxide, oxygen free radicals, proteolysis, apoptosis, and so on play important roles. There are also gene expressions following cerebral ischemia, such as the immediately early gene, heat shock protein, cytokines, adhesion molecule, and growth factor, etc. In vessels of the ischemic brain, activation of platelets, leukocytes, the coagulation cascade, and fibrin generation occur and aggravate the cerebral microcirculatory disturbance. Treatment of acute ischemic stroke must be based on the clinical type (atherothrombotic, lacunar or cardioembolic) and the time after onset. Fibrinolysis by tissue plasminogen activator (intravenous administration) is approved in the USA for patients with cerebral infarction within 3 hours after onset. Efficacy of anticoagulant therapy using heparin was not verified by the International Stroke Trial (IST). In Japan selective anti-thrombin agent (argatroban) is used in patients with atherothrombotic cerebral infarction within 48 hours after onset. Results of IST and Chinese Acute Stroke Trial (CAST) showed aspirin within 48 hours after onset of cerebral infarction reduced recurrence of ischemic stroke during the acute stage and death within 6 months.
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PMID:[Recent advances in pathophysiology and treatment of acute ischemic stroke]. 1034 38

Recently published large clinical trials of heparin and aspirin in acute stroke-the International Stroke Trial, Chinese Acute Stroke Trial, and Trial of ORG 10172 in Acute Stroke Treatment--fail to show a net benefit from heparin. None of these trials used i.v., dose-adjusted, unfractionated heparin as generally employed in the United States. However, the control groups in these trials provide data on acute stroke recurrence in large numbers of patients, and these stroke recurrence rates can be used to establish an upper limit for the potential efficacy of antithrombotic therapy. The rates of recurrent ischemic stroke in the control groups of these trials were low, ranging from 0.6 to 2.2% per week. The low rates of recurrent stroke observed in these groups, coupled with the morbidity and mortality associated with i.v. heparin in this patient population, argue against routine use of i.v. heparin in the acute stroke period.
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PMID:Intravenous heparin for acute stroke: what can we learn from the megatrials? 1075 Dec 80

Financial constraints at our institution prompted us to evaluate the management of patients referred to the Acute Stroke Service because of transient ischaemic attack (TIA). We analysed age, gender, length of stay, hospital costs, discharge disposition and stroke recurrence for all cases of TIA admitted to the Acute Stroke Service between January 1, 1994, and December 31, 1996. During this time, 110 cases of TIA were admitted. All had a CT head scan, 60% had carotid Doppler ultrasound, and 30% had transthoracic echocardiography. No patients admitted with TIA died, and 92% were discharged home. The average annual cost of in-patient management of TIA was 328,000 Canadian dollars, of which 95% were accounted for by the cost of the hospital bed alone. If hospitalisation of patients with TIA could be reduced, significant cost-savings could be realised.
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PMID:What is the cost of admitting patients with transient ischaemic attacks to hospital? 1039 7

This review analyses the benefit-risk ratio of antiplatelet drugs in secondary stroke prevention and is based on the published data from eight large stroke prevention trials. In patients with prior transient ischaemic attack (TIA) or stroke, aspirin prevented one to two vascular events (stroke, AMI, or vascular death) per 100 treatment-years with an excess risk of fatal and severe bleeds of 0. 4-0.6 per 100 treatment-years. The gastrointestinal bleeding risk was significantly lower with ticlopidine and clopidogrel, which were both somewhat more effective than aspirin in the prevention of vascular events. The combination of dipyridamole and aspirin prevented 2.82 strokes at the expense of an excess risk of 0.61 (95% CI = 0.27-0.95) fatal or severe bleeds per 100 treatment-years. In the acute phase of stroke, the aspirin-associated risk of haemorrhagic complications was much increased compared with that in the stable phase after stroke, with 0.48 (95% CI = 0.13-0.83) fatal or severe bleeds per 100 treated patients for the first 4 weeks after stroke in the Chinese Acute Stroke Trial and 0.41 (95% CI = 0. 05-0.77) in the International Stroke Trial. Still, there was a net benefit with the prevention of about one death or non-fatal ischaemic stroke per 100 treated patients.
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PMID:Bleeding complications in secondary stroke prevention by antiplatelet therapy: a benefit-risk analysis. 1047 91

Thrombolytic therapy with recombinant tissue plasminogen activator (rtPA) is approved in the United States for treatment of acute ischemic stroke. Approval was granted after a large, randomized, placebo-controlled study by the National Institute of Neurological Disorders and Stroke (NINDS) showed a significant improvement in 3-month outcomes with rtPA despite a significant risk for symptomatic hemorrhage. Two other trials, the first and second European Cooperative Acute Stroke Study (ECASS I and II), have shown comparable results, but neither was statistically positive for the predefined primary end point. An analysis of the risk/benefit profile of rtPA therapy based on the results of these three trials indicates that the treatment is effective and, when administered within 3 hours of symptom onset at a dose of 0.9 mg/kg, the benefits by far outweigh the risks for eligible patients. Even with the 6-hour time window of the two ECASS trials, a combined analysis of the three studies shows the number of disabled or dead patients to be significantly reduced. Preliminary data collected on the use of rtPA outside of clinical trials in the United States and Europe suggest that, when rtPA is used according to the trial protocol, the risks and benefits are similar to those observed in clinical trials. However, even within the United States, rtPA is underutilized. The most substantial treatment barrier is the narrow time window, which may be expanded if long-term experience shows that this is possible. Most stroke patients arrive at the hospital too late to be eligible for screening and treatment. Education of the public and physicians may help to overcome this difficulty.
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PMID:Thrombolysis in acute ischemic stroke: controlled trials and clinical experience. 1053 43


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