Risk Of Symptomatic Intracranial Hemorrhage Research Articles

Alteplase for acute ischemic stroke

Alteplase, an intravenously administered form of recombinant tissue plasminogen activator (rt-PA), remains the only US FDA-approved thrombolytic treatment for acute ischemic stroke within 3 h of symptom onset. Patients treated with intravenous rt-PA are at least 30% more likely to have minimal or no disability at 3 months compared with placebo. Despite an increased risk of symptomatic intracranial hemorrhage, rt-PA does not increase mortality. The benefit achieved with rt-PA is cost effective and sustained 1 year after treatment. Despite its clear benefit, rt-PA remains underutilized. Although the future of acute ischemic stroke treatment will most likely involve a multi-faceted treatment approach, the primary objective remains to establish recanalization of the involved vessel. For patients with acute ischemic stroke within the first 3 h of symptom onset, rt-PA remains the first step in accomplishing this goal.

Response

Response

Ancrod: A Potential Treatment for Acute, Ischemic Stroke from Snake Venom

The direct effect of ancrod is defibrinogenation. This results in several secondary effects that differentiate ancrod from typical thrombolytics such as rt-PA. The combined actions of indirect fibrinolysis, reduced fibrin deposition, and decreased blood viscosity represent a constellation of actions that should be beneficial in a variety of thrombotic conditions. The clinical condition explored most thoroughly in recent years with ancrod has been its acute application to ischemic stroke. Two clinical studies (one of them with a 6 h time-to-treatment window) have demonstrated significant benefit in increasing the proportion of patients alive and disability-free at 3 months, but higher doses of the drug appear to increase the risk of symptomatic intracranial hemorrhage and reduce efficacy. Although the evidence is not conclusive, it suggests that, with modified dosing, ancrod could yield a favorable risk–benefit ratio in stroke by limiting the risk of symptomatic intracranial hemorrhage.

Intra-Arterial Thrombolytic Therapy in Peri-Coronary Angiography Ischemic Stroke

Intra-arterial thrombolysis (IAT) for peri-coronary angiography (CA) stroke may be safe and efficacious. However, IAT may increase the risk of intracranial hemorrhage (ICH). A retrospective study was performed involving 3 university hospitals. All peri-CA IAT-treated cases were identified. Patient demographics, stroke severity, angiographic findings, thrombolytic use, modified Rankin Scale (mRS), ICH, and mortality were determined. A total of 21 patients with post-left CA stroke were treated with IAT (mean age 71.8+/-12.3 years). Arterial occlusion was found in 14 (66.7%) and 7 (33.3%) of the anterior and posterior circulation, respectively. Mean time-to-therapy was 36+/-12 minutes from the time the neurological deficit was noted. mRS < or =2 occurred in 10 of 21 (48%) patients. Patients with younger age and shorter time-to-IAT had more complete arterial recanalization and clinical recovery. Symptomatic ICH occurred in 3 (14%) cases, and 4 (19%) patients died. Peri-CA IAT appears to be feasible and safe without increased risk of symptomatic ICH and death when compared with the previously reported IAT literature.

Response

Response

Thrombolyse et infarctus cérébral aigu

Thrombolytic therapy are the most important advance in the management of acute ischemic stroke and has been evaluated in several randomised trials. Thrombolysis with recombinant tissue plasminogen activator (rt-Pa) is effective within 3 h of onset of ischemic stroke and this efficacy is similar between different stroke subtypes. New trials will determine if extension of this time-window can be substantiated. Therapy beyond the 3-hour window, with intra-arterial thrombolysis, appears to improve outcome but are applicable to selected group of patients. Thrombolytic drugs can also carry an important risk (5 % to 10 %) of brain hemorrhage and edema that can prove fatal. The risk of symptomatic intracranial hemorrhage is directly proportional to stroke severity and inversely proportional to time to treatment. There is a growing interest in the use of MRI in acute ischemic stroke. It helps identify location of early cerebral ischemia and provides valuable information not only of the penumbra but also of vessel occlusion. Its use might help in selecting patients who will benefit most from treatment such as thrombolysis. In spite of these results, community use of thrombolytic therapy remains dismally low. Many physicians and medical centers are not presently equipped or willing to give thrombolytic drugs for stroke treatment. Increasing stroke awareness in the community, creating stroke unit and physicians education are necessary to extend the effective use of acute treatment in cerebral infarct to a larger group of patients.

Anticoagulants versus antiplatelet agents for acute ischaemic stroke.

Antiplatelet agents produce a small, but worthwhile benefit in long-term functional outcome and survival, and have become standard treatment for acute ischaemic stroke. Anticoagulants are often used as an alternative treatment, despite evidence that they are ineffective in producing long-term benefits. We wanted to review trials which have directly compared anticoagulants and antiplatelet agents, to assess whether any anticoagulant regimen offers net advantages over antiplatelet agents, overall or in some particular category of patients (e.g. patients with atrial fibrillation). a) To assess the effectiveness of anticoagulants compared with antiplatelet agents in acute ischaemic stroke b) To assess whether the addition of anticoagulants to antiplatelet agents offers any net advantage over antiplatelet agents alone. We searched the Cochrane Stroke Group Trials Register, the Cochrane Controlled Trials Register (Central/CCTR), the trials register held by the Antithrombotic Therapy Trialists' Collaboration, MEDLINE (1966-2000), and EMBASE (1980-2000). All searches were performed during April and May 2001. Truly unconfounded, randomised-controlled trials comparing anticoagulants with antiplatelet agents, or anticoagulants and antiplatelet agents with antiplatelet agents alone, given within 14 days of onset of presumed or confirmed ischaemic stroke. Both reviewers independently selected trials for inclusion in the review, assessed trial quality and extracted data. A total of 16,558 patients from four trials contributed to the analyses. The methodological quality was high in all four trials. The anticoagulants tested were unfractionated heparin (UFH) and low molecular-weight heparin. Aspirin was used as control in all trials. Overall, there was no evidence that anticoagulants were superior to aspirin in reducing 'death or dependency' at long-term follow-up (odds ratio [OR] 1.07, 95% confidence interval [95% CI] 0.98-1.15). Compared with aspirin, anticoagulants were associated with a small but significant increase in the number of deaths at the end of follow-up (OR 1.10, 95% CI 1.01-1.29), equivalent to 20 more deaths (95% CI 0-30) per 1000 patients treated; a significant increased risk of symptomatic intracranial haemorrhage (OR 2.35, 95% CI 1.49-3.46); and a non-significant increased risk of 'any recurrent stroke' during treatment (OR 1.20, 95% CI 0.99-1.46). These neutral or adverse effects outweighed a small, but significant effect on symptomatic deep vein thrombosis (OR 1.20, 95% CI 0.07-0.58), equivalent to 10 fewer (95% CI 0-30) DVTs by 14 days per 1000 patients treated with anticoagulants instead of aspirin. Subgroup analysis could not identify any type, dose, or route of administration of anticoagulants associated with net benefit, or any benefit in patients with atrial fibrillation. Overall, the combination of UFH and aspirin did not appear to be associated with a net advantage over aspirin alone. A subgroup analysis showed that, compared with aspirin, the combination of low-dose UFH and aspirin was associated with a marginally significant reduced risk of 'any recurrent stroke' (OR 0.75, 95% CI 0.56-1.03) and a marginally significant reduced risk of death at 14 days (OR 0.84, 95% CI 0.69-1.01), and with no clear adverse effect on death at end of follow-up (OR 0.98, 95% CI 0.85-1.12). Anticoagulants offered no net advantages over antiplatelet agents in acute ischaemic stroke. The combination of low-dose UFH and aspirin appeared in a subgroup analysis to be associated with net benefits compared with aspirin alone, and this merits further research.

Risk factors for severe hemorrhagic transformation in ischemic stroke patients treated with recombinant tissue plasminogen activator: a secondary analysis of the European-Australasian Acute Stroke Study (ECASS II).

Intravenous thrombolysis with recombinant tissue plasminogen activator (rtPA) improves the outcome for ischemic stroke patients who can be treated within 3 hours of symptom onset. The efficacy of thrombolysis has been demonstrated despite an increased risk of severe hemorrhagic transformation (HT) in patients treated with rtPA. We performed an analysis of risk factors for severe HT in the second European-Australasian Acute Stroke Study (ECASS II). HTs were classified by using clinical and radiological criteria as follows: hemorrhagic infarction (HI), parenchymal hemorrhage (PH), and symptomatic intracranial hemorrhage (SICH). Potential risk factors for HT were tested by stepwise logistic regression analysis, including rtPA-by-variable interactions. In addition, the distribution of bad outcome (modified Rankin score 5 to 6) at day 90 was stratified according to each category of HT. PH and SICH but not HI were associated with rtPA. Also, PH and SICH but not HI were more severe in rtPA-treated patients than in those receiving placebo. Risk factors for PH were rtPA, extent of parenchymal hypoattenuation on baseline CT, congestive heart failure, increasing age, and baseline systolic blood pressure. The risk of PH on rtPA was increased in older patients and in those who were treated with aspirin before thrombolysis. Risk factors for SICH were rtPA, congestive heart failure, extent of parenchymal hypoattenuation, and increasing age. The risk of SICH on rtPA was increased in patients who were treated with aspirin before thrombolysis. This secondary analysis of ECASS II has confirmed the importance of the extent of hypoattenuation as a risk factor for severe HT. The findings also suggest that older patients and those who have used aspirin before stroke are at higher risk of a severe HT on rtPA.

Cost-Utility analysis of tissue plasminogen activator therapy for acute ischaemic stroke: a Canadian healthcare perspective.

There are over 40000 ischaemic strokes annually in Canada, which result in significant morbidity, mortality and burden to the healthcare system. A recent, large clinical trial has evaluated tissue plasminogen activator (t-PA) intravenously for the treatment of acute ischaemic stroke with promising outcomes but with an increased risk of symptomatic intracranial haemorrhage. To compare clinical and economic outcomes of intravenous t-PA therapy (0.9 mg/kg, to a maximum of 90 mg, initiated within 3 hours of stroke onset) versus no t-PA for acute ischaemic stroke based on the outcomes achieved in the National Institute of Neurological Disorders and Stroke (NINDS) trial. A Markov model depicting the natural lifetime course after an initial acute ischaemic stroke. On the basis of this model, a simulated trial compared no t-PA with t-PA. A hypothetical cohort of 1000 patients with acute ischaemic stroke. Canadian healthcare system. Total acute stroke and post-stroke treatment costs and cumulative quality-adjusted life-years (QALYs). For a hypothetical cohort of 1000 patients, the estimated lifetime stroke costs were 103100000 Canadian dollars (SCan) [1999 values) in the t-PA arm ($Can103100 per patient) compared with SCan106900000 in the no t-PA arm ($Can106900 per patient), yielding a lifetime cost difference of $Can3800000 in favour of t-PA versus no t-PA (SCan3800 per patient). In the hypothetical cohort, t-PA treatment resulted in 13 130 QALYs versus 9670 QALYs with no t-PA treatment. This translated into a net benefit of 3460 additional QALYs per 1000 patients (3.46 QALYs per patient). No treatment, outcome or economic variables influenced the model outcome. From the standpoint of cost effectiveness, treatment of acute ischaemic stroke with intravenous t-PA is an economically attractive strategy.