Off-label thrombolysis is not associated with poor outcome in patients with stroke.
OBJECTIVE
Numerous contraindications included in the license of alteplase, most of which are not based on scientific evidence, restrict the portion of patients with acute ischemic stroke eligible for treatment with alteplase. We studied whether off-label thrombolysis was associated with poorer outcome or increased rates of symptomatic intracerebral hemorrhage compared with on-label use.


METHODS
All consecutive patients with stroke treated with intravenous thrombolysis from 1995 to 2008 at the Helsinki University Central Hospital were registered (n=1104). After excluding basilar artery occlusions (n=119), the study population included 985 patients. Clinical outcome (modified Rankin Scale 0 to 2 versus 3 to 6) and symptomatic intracerebral hemorrhage according to 3 earlier published criteria were analyzed with a logistic regression model adjusting for 21 baseline variables.


RESULTS
One or more license contraindications to thrombolysis was present in 51% of our patients (n=499). The most common of these were age >80 years (n=159), mild stroke National Institutes of Health Stroke Scale score <5 (n=129), use of intravenous antihypertensives prior to treatment (n=112), symptom-to-needle time >3 hours (n=95), blood pressure >185/110 mm Hg (n=47), and oral anticoagulation (n=39). Age >80 years was the only contraindication independently associated with poor outcome (OR, 2.18; 95% CI, 1.27 to 3.73) in the multivariate model. None of the contraindications were associated with an increased risk of symptomatic intracerebral hemorrhage.


CONCLUSIONS
Off-license thrombolysis was not associated with poorer clinical outcome, except for age >80 years, nor with increased rates of symptomatic intracerebral hemorrhage. The current extensive list of contraindications should be re-evaluated when data from ongoing randomized trials and observational studies become available.
Meretoja
Atte
A
Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland. atte.meretoja@fimnet.fi
Putaala
Jukka
J
Tatlisumak
Turgut
T
Atula
Sari
S
Artto
Ville
V
Curtze
Sami
S
Häppölä
Olli
O
Lindsberg
Perttu J
PJ
Mustanoja
Satu
S
Piironen
Katja
K
Pitkäniemi
Janne
J
Rantanen
Kirsi
K
Sairanen
Tiina
T
Salonen
Oili
O
Silvennoinen
Heli
H
Soinne
Lauri
L
Strbian
Daniel
D
Tiainen
Marjaana
M
Kaste
Markku
M
D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D005500:Follow-Up Studies; D006801:Humans; D008875:Middle Aged; D056687:Off-Label Use; D012042:Registries; D012307:Risk Factors; D020521:Stroke / Q000188:drug therapy* / Q000453:epidemiology; D015912:Thrombolytic Therapy / Q000009:adverse effects; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D055815:Young Adult
D010959:Tissue Plasminogen Activator