Impact of time to treatment on tissue-type plasminogen activator-induced recanalization in acute ischemic stroke

Background and purpose: Although tissue-type plasminogen activator (tPA) efficacy depends on time, it is unknown whether its effect on recanalization is time dependent. Information about likelihood of successful recanalization as a function of time to treatment may improve patient selection for advanced reperfusion strategies. We aimed to identify the impact of time to treatment on tPA-induced recanalization in patients with acute ischemic stroke.

Methods: Consecutive patients with intracranial acute occlusion treated with intravenous tPA underwent transcranial Doppler examination before and 1 hour after tPA administration. Patients were categorized according to occlusion localization in proximal and distal occlusion. Sequential analysis of recanalization according to time to treatment was performed for every 30-minute cutoff point.

Results: Overall (n=508), 54.3% had proximal and 45.7% had distal occlusion. Median time to treatment was 171.4±61.9 minutes, and 5.9% were treated >270 minutes. Recanalization occurred in 36.1% of patients. There was no linear association between time to treatment and time to recanalization, but sequential analysis showed that patients treated >270 minutes had a lower recanalization rate. Lower National Institutes of Health Stroke Scale score on admission (odds ratio [OR], 0.305; 95% confidence interval [CI], 0.1-0.933) and time to treatment ≤270 minutes (OR, 0.995; 95% CI, 0.99-0.999) emerged as independent predictors of recanalization. In patients with proximal occlusion, 41.8% recanalized. Time to treatment >90 minutes was associated with lower recanalization rate. However, only younger age (OR, 0.975; 95% CI, 0.952-0.999) and lower baseline National Institutes of Health Stroke Scale score (OR, 0.921; 95% CI, 0.855-0.993) independently predicted recanalization. In distal occlusion patients, male sex was the only independent predictor of recanalization (OR, 0.416; 95% CI, 0.195-0.887). None recanalized >270 minutes.

Conclusions: The effect of tPA on recanalization may decrease over time. Treatment >270 minutes predicted lack of recanalization, especially in distal occlusions.