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[Strategy for circulatory disturbance]
S Uchiyama1, M Yamazaki, M Iwata
1Department of Neurology, Neurological Institute, Tokyo Women's Medical University.
Insights
Thrombolytic therapy for acute ischemic stroke offers benefits in reducing disability but carries risks of hemorrhage. Newer agents and aspirin show promise, while anticoagulants have not demonstrated clear net benefits.
Area of Science:
- Neurology
- Cardiovascular Medicine
- Pharmacology
Background:
- Acute ischemic stroke presents significant morbidity and mortality.
- Effective treatments aim to restore blood flow and minimize brain damage.
- Thrombolytic and anticoagulant therapies are key areas of investigation.
Purpose of the Study:
- To review the efficacy and safety of various pharmacological interventions for acute ischemic stroke.
- To evaluate the net benefit of thrombolytic and anticoagulant therapies.
- To explore emerging treatments including newer thrombolytics, anticoagulants, and antiplatelet agents.
Main Methods:
- Meta-analysis of existing trials on thrombolytic therapy (Cochrane Stroke Group).
- Review of trials investigating intravenous (i.v.) tissue plasminogen activator (tPA).
- Analysis of studies on intra-arterial pro-urokinase, anticoagulants, aspirin, and abciximab.
Main Results:
- Thrombolytic therapy reduces disability but increases hemorrhage risk; overall net benefit observed.
- Intravenous tPA may offer a better risk-benefit profile.
- Anticoagulant therapy showed no clear net short or long-term benefit.
- Aspirin demonstrated a modest effect in reducing death or dependency.
- Emerging agents like pro-urokinase and argatroban show potential in specific patient groups.
Conclusions:
- Thrombolytic therapy provides a net reduction in death or dependency despite increased hemorrhage risks.
- Further research into third-generation thrombolytics and agents like abciximab is ongoing.
- Current evidence does not support routine anticoagulant therapy for acute ischemic stroke, though specific agents may benefit subgroups.
Abstract:
A meta-analysis by the Cochrane Stroke Group (CSG) showed that thrombolytic therapy increased deaths as well as symptomatic and fatal intracranial hemorrhage within the first seven to 10 days and at final follow-up, although these risks are offset by a reduction in disability in survivors, so that there is overall a significant net reduction in the proportion of patients dead or dependent. Trials testing intravenous (i.v.) tPA suggest that it may be associated with less hazard and more benefit. A recent trial demonstrated that intra-arterial pro-urokinase improved long-term outcome in patients with M 1 or M 2 occlusion within 6 hours of onset. Trials of the third generation of thrombolytic agents are ongoing in patients with acute ischemic stroke. The latest CSG's meta-analysis showed that immediate anticoagulant therapy in patients with acute ischemic stroke was not associated with net short or long-term benefit because there was no evidence that anticoagulant therapy reduced deaths or non-fatal stroke during treatment or patients dead or dependent at the end of follow-up. However, an i.v. low-molecular-weight heparinoid showed a trend toward improving long-term outcome in subgroup of patients with atherothrombotic stroke. The thrombin inhibitor argatroban was proven to be comparable to the thromboxane A2 synthetase inhibitor ozagrel in the effect on the outcome at one month in patients with atherothrombotic stroke within 48 hours of onset in Japan, and a trial of the agent is ongoing in patients with ischemic stroke within 12 hours of onset in the United States. Two large trials of aspirin in patients with ischemic stroke within 48 hours of onset indicated that aspirin had a modest effect on reducing patients dead or dependent at the end of follow-up. An international trial of abciximab, a monoclonal antibody directed against platelet glycoprotein IIb/IIIa, is ongoing in patients with ischemic stroke within 6 hours of onset.