Effect of intravenous tirofiban and aspirin in reducing short-term and long-term neurologic deficit in patients with ischemic stroke: a double-blind randomized trial.
BACKGROUND
Thrombolysis with rt-PA is the only approved pharmacological therapy for acute ischemic stroke presently administrable in a 3-hour window (very recently extended to 4.5 h). After this time, the choice is limited to endovascular treatment and antiplatelet drugs, mainly aspirin (ASA), the efficacy of which in the acute phase of stroke has poorly been evaluated. We compared the efficacy of tirofiban, a GP-IIb/IIIa inhibitor, and ASA, with both drugs being administered within 6 h.


METHODS
150 patients were randomly assigned to treatment with tirofiban or ASA, both given for 3 days in a double-blind regimen. Major inclusion criteria were stroke onset within 6 h and a baseline National Institute of Health Stroke Scale (NIHSS) score of 5-25. Outcome variables were the proportion of patients with a NIHSS score reduction of > or =4 points after 72 h, and the proportion of patients with an mRS score of 0-1 at 3 months.


RESULTS
The trial, originally planned to enroll 300 patients, was halted after enrollment of 150 patients at interim analysis due to the lack of a trend difference between the 2 treatment groups. Neurological improvement at 72 h was observed in 56% of the patients in each group. At the 3-month follow-up, minimal or absent disability was seen in 45% of the patients in the tirofiban group and 53% in the ASA group; these differences were not statistically significant. Three-month mortality was the same in both groups (10.6%); the rates of symptomatic intracranial hemorrhage were 1% (tirofiban) and 4% (ASA).


CONCLUSIONS
In spite of the fact that the null hypothesis was not supported by our data, we found results supporting the safety (and potential efficacy) of ASA and tirofiban when used in the first hours of acute ischemic stroke. However, this needs to be confirmed by further studies.
Torgano
G
G
Department of Emergency Medicine, Fondazione IRCCS Ospedale Maggiore Policlinico Mangiagalli e Regina Elena, Milano, Italy. giuseppe.torgano@policlinico.mi.it
Zecca
B
B
Monzani
V
V
Maestroni
A
A
Rossi
P
P
Cazzaniga
M
M
Manganaro
D
D
Boiti
C
C
Zilioli
E
E
Borutti
G
G
Falaschi
F
F
Mandelli
C
C
D000368:Aged; D000369:Aged, 80 and over; D001241:Aspirin / Q000008:administration & dosage* / Q000009:adverse effects; D002545:Brain Ischemia / Q000150:complications / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D016009:Chi-Square Distribution; D004185:Disability Evaluation; D004311:Double-Blind Method; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D057239:Early Termination of Clinical Trials; D005260:Female; D005343:Fibrinolytic Agents / Q000008:administration & dosage* / Q000009:adverse effects; D017052:Hospital Mortality; D006801:Humans; D020300:Intracranial Hemorrhages / Q000209:etiology; D007558:Italy; D008297:Male; D008875:Middle Aged; D010975:Platelet Aggregation Inhibitors / Q000008:administration & dosage* / Q000009:adverse effects; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000037:antagonists & inhibitors; D020127:Recovery of Function; D020521:Stroke / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality / Q000503:physiopathology; D013997:Time Factors; D000077466:Tirofiban; D016896:Treatment Outcome; D014443:Tyrosine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives*
D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D014443:Tyrosine; D000077466:Tirofiban; D001241:Aspirin