Background: Intravenous thrombolysis (IVT) is not approved for acute ischemic stroke in certain patient groups due to in- and exclusion criteria from mostly early clinical trials. In a real-life setting, we analyzed frequencies, outcomes and complications of off-label-IVT compared to on-label-IVT and no IVT to contribute to rational decision-making regarding patient selection for IVT.
Methods: Patients in the Berlin Specific Acute Therapy in Ischemic or hAemorrhagic stroke with Long-term follow-up registry were divided into three groups (on-label, off-label, non-IVT-treated). Off-label criteria were age > 80 years, time from onset >4.5 h, mild (National Institutes of Health Stroke Scale [NIHSS] < 5) or severe (NIHSS > 25) stroke, and a history of prior stroke and diabetes mellitus, as those criteria applied during the study period. Outcomes of interest were the 90-day modified Rankin Scale (mRS), symptomatic intracranial hemorrhage (sICH), in-hospital- and 90-day-mortality. After multiple imputation, we performed multivariable logistic regression to calculate adjusted common odds ratios (cOR) with 95% confidence intervals (CI) for mRS and risk ratios for secondary outcome measures.
Results: We analyzed 1875 on-label, 2881 off-label, and 4639 non-treated patients. The most common off-label-criteria were mild symptoms (44.6%) and older age (33.6%). Off-label-treated patients had no worse functional outcome when compared to on-label-treated patients (cOR 0.89, CI 0.78-1.02), but better outcome compared to non-treated patients (cOR 0.83, CI 0.76-0.91). No associations were found for sICH or mortality.
Conclusions: Our results suggest a beneficial effect of off-label treatment in clinical practice, which warrants further investigation into treatment in relevant subgroups and an extension of the product license.
Keywords: Ischemic stroke; acute stroke therapy; off-label; stroke; tPA; thrombolysis.