Off-label intravenous thrombolysis in acute stroke

Background and purpose: Therapy for stroke with intravenous tissue plasminogen activator (IV-tPA) is hampered by tight licensing restrictions; some of them have been discussed in recent literature. We assessed the safety and effectiveness of off-label IV-tPA in the clinical settings. Methods: Retrospective analysis of all the patients treated with IV-tPA at our Stroke Unit. Patients were divided into two groups by licence criteria [on-label group (OnLG), off-label group (OffLG)]. Primary outcome measures were symptomatic intracranial haemorrhages (sICH), major systemic haemorrhages, modified Rankin scale (mRS) and mortality rate at 3 months. Results: Five hundred and five patients were registered, 269 (53.2%) were assigned to OnLG and 236 (46.9%) to OffLG. Inclusion criteria for the OffLG were aged > 80 years (129 patients), time from onset of symptoms to treatment over 3 h (111), prior oral anticoagulant treatment with International Normalised Ratio <= 1.7 (41), combination of previous stroke and diabetes mellitus (14), surgery or severe trauma within 3 months of stroke (13), National Institutes of Health Stroke Scale score over 25 (11), intracranial tumours (5), systemic diseases with risk of bleeding (7) and seizure at the onset of stroke (2). No significant differences were identified between both groups regarding the proportion of sICH (OnLG 2.2% vs. OffLG 1.6%, P = 0.78) or the 3-month mortality rate (11.1% vs. 19%: odds ratio (OR), 1.49; 95% CI, 0.86-2.55; P = 0.14). Multivariate analysis showed no significant differences in functional independence at 3 months between both groups (mRS <3 64.3% vs. 50.4%: OR mRS > 2 1.7; 95% CI, 0.96-2.5; P = 0.07). Conclusion: Intravenous thrombolysis may be safe and efficacious beyond its current label restrictions.