Off-Label Thrombolysis for Acute Ischemic Stroke: Rate, Clinical Outcome and Safety Are Influenced by the Definition of ‘Minor Stroke’

Abstract

Background: Several contraindications for intravenous thrombolysis are not based on controlled trials. Specialized stroke centers often apply less restrictive criteria. The aim of our study was to analyze how many patients at our institution receive off-label thrombolysis. In addition, clinical outcome and safety data were compared to those from patients treated on-label, and the influence of different definitions of ‘minor stroke’ were examined. Methods: Consecutive thrombolysis patients treated between January 2006 and January 2010 were included. Patients treated off-label were compared to patients given on-label therapy according to the European license. Since no specified definition for ‘minor neurological deficit’ exists in the license, two distinct definitions were considered off-label, i.e. National Institutes of Health Stroke Scale score (NIHSSS) <1 (definition 1) and NIHSSS ≤4 (definition 2). Results: Of a total of 422 patients, 232 (55%) were treated off-label. The most prevalent off-label criteria (OLCs) were the following: age >80 years (n = 113), minor stroke (definition 1, n = 3; definition 2, n = 84), elevated blood pressure necessitating aggressive treatment (n = 75), time window >3 h (n = 71) and major surgery or trauma within the preceding 3 months (n = 20). In group comparisons, off-label patients had an overall worse outcome using definition 1 for minor stroke, while there was no difference when definition 2 was applied. In multivariate analysis, off-label therapy (definition 1) in general and age >80 years were independent predictors of poor outcome. None of the contraindications were associated with an increased bleeding risk. Conclusions: Off-label therapy is frequently applied at our center and is not associated with higher complication rates. Overall outcome of off-label treatment largely depends on the definition used for minor stroke. Besides age >80 years, a known poor prognostic factor, no other specific OLC was associated with poor outcome. Our data suggest that the criteria in the European license may be too restrictive.

Intravenous Thrombolysis for Stroke Recurring Within 3 Months From the Previous Event

“…20,[28][29][30][31][32] In our cohort, representative of real-life stroke care in Central and Eastern Europe, only 2% of patients treated with r-tPA had previous stroke ≤3 months, which is in line with other studies. 4,[9][10][11]28 Therefore, our findings indirectly confirm that patients with previous stroke constitute potentially large and undertreated group. According to our data, patients with a history of previous stroke ≤3 months were more burdened with vascular risk factors and had worse prestroke functional status compared with those with first-ever stroke, which is partially consistent with observations in unselected stroke cases.…”

“…1,2 Its increasing use over the years allowed to accumulate a considerable amount of data supporting off-label treatment in particular situations, [3][4][5][6][7][8][9][10][11] including patients with previous stroke or preexisting…”

Guidelines for the Early Management of Patients With Acute Ischemic Stroke

“…[487][488][489][490][491][492][493] These groups report the use of fibrinolysis in patients with conditions including extreme age (>80 years), prior stroke and diabetes mellitus, minor stroke, rapidly improving stroke symptoms, recent myocardial infarction, major surgery or trauma within the preceding 3 months, and oral anticoagulation use. Overall, the outcomes in the treated patients with these contraindications were better than nontreated "controls" from registry data.…”

Antiplatelet therapy strategies for ischemic stroke

“…Многолетний опыт успешного применения системно-го тромболизиса при ИИ стал предпосылкой для его ис-пользования за пределами установленных критериев (thrombolysis off label) [17][18][19], так как, по мнению экспер-тов, ряд противопоказаний для его проведения являются не абсолютными, а относительными. Среди них называют воз-раст старше 80 лет, легкие или быстро регрессирующие нев-рологические симптомы (<5 баллов по шкале инсульта NIH), значительно выраженные неврологические симпто-мы (>25 баллов по шкале инсульта NIH), эпилептический припадок, черепно-мозговая травма или хирургическая операция в последние 3 мес, инсульт и сахарный диабет (СД) в анамнезе, прием антикоагулянтов [18,19].…”

“…Среди них называют воз-раст старше 80 лет, легкие или быстро регрессирующие нев-рологические симптомы (<5 баллов по шкале инсульта NIH), значительно выраженные неврологические симпто-мы (>25 баллов по шкале инсульта NIH), эпилептический припадок, черепно-мозговая травма или хирургическая операция в последние 3 мес, инсульт и сахарный диабет (СД) в анамнезе, прием антикоагулянтов [18,19].…”