Background: The current European license for alteplase in acute ischemic stroke excludes from treatment large groups of patients. Nevertheless, in everyday practice, many patients receive off-label thrombolysis at the physician's discretion.
Aim: Our aim was to evaluate safety and effectiveness of intravenous alteplase in patients not fully adhering to the drug license compared with those treated strictly according to the license in Central and Eastern Europe.
Methods: We analyzed the data contributed to Safe Implementation of Thrombolysis in Stroke registry from nine countries between February 2003 and February 2010. Statistical analysis included multivariate logistic regression.
Results: Of 5594 consecutive patients, 1919 patients (34·3%) not fully adhered to the license. The most frequent deviations were: time-to-treatment >3 h (13·1%), use of intravenous antihypertensives (8·3%), age >80 years (7·3%), oral anticoagulation (4·2%), a previous stroke with concomitant diabetes (3·9%), and previous stroke <three-months (2·7%). The off-label group showed a significantly higher rate of symptomatic intracranial haemorrhage, which was not confirmed in the multivariate analysis. License nonadherence significantly increased the risk of death or dependency (odds ratio 1·26; 95% confidence interval: 1·08-1·48), with a trend for increased mortality (odds ratio 1·17; 95% confidence interval: 0·97-1·42). Isolated time-to-treatment >3 h was an independent predictor of unfavorable outcome (odds ratio 1·32; 95% confidence interval: 1·01-1·71).
Conclusion: Our findings show that patients not fully adhering to the European license are not at increased risk of symptomatic intracranial haemorrhage but achieve less favorable outcome. Some contraindications appear more redundant than others. However, the final conclusions about safety and effectiveness should be based on the results of ongoing randomized trials.
© 2012 The Authors. International Journal of Stroke © 2012 World Stroke Organization.