Safety and feasibility of a lower dose intravenous TPA therapy for ischemic stroke beyond the first three hours.
BACKGROUND
The most common reason that patients do not receive intravenous tissue plasminogen activator (TPA) is the inability to meet the strict 3-hour treatment window. The risk/benefit ratio is more unfavorable beyond this time, but some patients might still benefit. We designed a pilot study with the hypothesis that lower dose TPA might be safe in selected patients treated beyond 3 h.


METHODS
To determine the range of symptomatic hemorrhage and good outcome, we prospectively gave i.v. TPA 0.6 mg/kg up to 60 mg (15% bolus, 85% infusion over 30 min) to patients with ischemic stroke beyond the first 3 h after last known to be normal. Other eligibility criteria were: NIH Stroke Scale > or =4, normal head CT scan, and clinical suspicion or transcranial Doppler (TCD) evidence of a proximal arterial occlusion.


RESULTS
28 patients were treated, median age 65 (range 24-88) years, median baseline NIHSS score 18 (range 7-34) points. TPA bolus was given 372 +/- 158 min after stroke onset (range 189-720). Symptomatic hemorrhage occurred in 3/28 (11%) patients, including 1 fatal bleed. Overall mortality was 6/28 (21%). Partial or complete recanalization was found in 8/20 (40%) TCD monitored patients within 2 h after TPA bolus. Early major improvement occurred in 4/28 (14%) patients.


CONCLUSIONS
Lower dose i.v. TPA in patients presenting beyond 3 h carries a risk of intracerebral hemorrhage. However, recanalization with dramatic recovery can still occur.
Uchino
Ken
K
Stroke Program, Department of Neurology, University of Texas-Houston Medical School, USA. uchinok@upmc.edu
Alexandrov
Andrei V
AV
Garami
Zsolt
Z
El-Mitwalli
Ashraf
A
Morgenstern
Lewis B
LB
Grotta
James C
JC
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000188:drug therapy* / Q000453:epidemiology; D005240:Feasibility Studies; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D006801:Humans; D007275:Injections, Intravenous; D008875:Middle Aged; D010865:Pilot Projects; D011446:Prospective Studies; D012307:Risk Factors; D020521:Stroke / Q000188:drug therapy* / Q000453:epidemiology; D015912:Thrombolytic Therapy; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000009:adverse effects
D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator