Thrombolytic therapy for acute ischemic stroke beyond three hours.
BACKGROUND
Ischemic cerebrovascular accidents remain a leading cause of morbidity and mortality. Thrombolytic therapy for acute ischemic stroke within 3h of symptom onset of highly select patients has been advocated by some groups since 1995, but trials have yielded inconsistent outcomes. One recent trial demonstrated significant improvement when the therapeutic window was extended to 4.5h.


OBJECTIVE
Does the intravenous systemic administration of tPA within 4.5h to select patients with acute ischemic stroke improve functional outcomes?


METHODS
All randomized controlled trials enrolling patients within 4.5h were identified, in addition to a meta-analysis of these trial data.


RESULTS
The National Institute of Neurological Disorders and Stroke (NINDS) and European Cooperative Acute Stroke Study III (ECASS III) clinical trials demonstrated significantly improved outcomes at 3 months, with increased rates of intracranial hemorrhage, whereas ECASS II and the Acute Noninterventional Therapy in Ischemic Stroke (ATLANTIS) study showed increased hemorrhagic complications without improving outcomes. Meta-analysis of trial data from all ECASS trials, NINDS, and ATLANTIS suggest that thrombolysis within 4.5h improves functional outcomes.


CONCLUSIONS
Ischemic stroke tPA treatment within 4.5h seems to improve functional outcomes and increases symptomatic intracranial hemorrhage rates without significantly increasing mortality.
Carpenter
Christopher R
CR
Washington University School of Medicine, St. Louis, MO, USA.
Keim
Samuel M
SM
Milne
William Kenneth
WK
Meurer
William J
WJ
Barsan
William G
WG
D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D002545:Brain Ischemia / Q000150:complications*; D019317:Evidence-Based Medicine; D005260:Female; D006801:Humans; D008875:Middle Aged; D016032:Randomized Controlled Trials as Topic; D020521:Stroke / Q000188:drug therapy* / Q000209:etiology; D015912:Thrombolytic Therapy; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage; D016896:Treatment Outcome
D010959:Tissue Plasminogen Activator