Off-label thrombolysis versus full adherence to the current European Alteplase license: impact on early clinical outcomes after acute ischemic stroke.
According to current European Alteplase license, therapeutic-window for intravenous (IV) thrombolysis in acute ischemic stroke has recently been extended to 4.5 h after symptoms onset. However, due to numerous contraindications, the portion of patients eligible for treatment still remains limited. Early neurological status after thrombolysis could identify more faithfully the impact of off-label Alteplase use that long-term functional outcome. We aimed to identify the impact of off-label thrombolysis and each off-label criterion on early clinical outcomes compared with the current European Alteplase license. We conducted an analysis on prospectively collected data of 500 consecutive thrombolysed patients. The primary outcome measures included major neurological improvement (NIHSS score decrease of ≤8 points from baseline or NIHSS score of 0) and neurological deterioration (NIHSS score increase of ≥4 points from baseline or death) at 24 h. We estimated the independent effect of off-label thrombolysis and each off-label criterion by calculating the odds ratio (OR) with 2-sided 95% confidence interval (CI) for each outcome measure. As the reference, we used patients fully adhering to the current European Alteplase license. 237 (47.4%) patients were treated with IV thrombolysis beyond the current European Alteplase license. We did not find significant differences between off- and on-label thrombolysis on early clinical outcomes. No off-label criteria were associated with decreased rate of major neurological improvement compared with on-label thrombolysis. History of stroke and concomitant diabetes was the only off-label criterion associated with increased rate of neurological deterioration (OR 5.84, 95% CI 1.61-21.19; p = 0.024). Off-label thrombolysis may be less effective at 24 h than on-label Alteplase use in patients with previous stroke and concomitant diabetes. Instead, the impact of other off-label criteria on early clinical outcomes was not different compared with current European Alteplase license.
SSO Stroke Unit, U.O. Neurologia d.O., DAI di Neuroscienze, Azienda Ospedaliera Universitaria Integrata, Piazzale A. Stefani 1, 37126, Verona, Italy, manuel_cappellari@libero.it.
Manuel
M
Cappellari
Giuseppe
G
Moretto
Nicola
N
Micheletti
Francesco
F
Donato
Giampaolo
G
Tomelleri
Giosuè
G
Gulli
Monica
M
Carletti
Giovanna Maddalena
GM
Squintani
Tiziano
T
Zanoni
Sarah
S
Ottaviani
Silvia
S
Romito
Giorgio
G
Tommasi
Anna Maria
AM
Musso
Luciano
L
Deotto
Giuseppe
G
Gambina
Domenico Sergio
DS
Zimatore
Paolo
P
Bovi
D000368:Aged; D000369:Aged, 80 and over; D002545:Brain Ischemia / Q000188:drug therapy* / Q000453:epidemiology; D005260:Female; D005343:Fibrinolytic Agents / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D008875:Middle Aged; D056687:Off-Label Use; D011446:Prospective Studies; D020521:Stroke / Q000188:drug therapy* / Q000453:epidemiology; D015912:Thrombolytic Therapy; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000009:adverse effects / Q000627:therapeutic use*
D005343:Fibrinolytic Agents; D010959:Tissue Plasminogen Activator