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Background: Extending the therapeutic window of intravenous thrombolysis for acute ischemic stroke beyond the established 4.5-hour limit is of critical importance in order to increase the proportion of thrombolysed stroke patients. In this setting, the capacity of MRI to select acute stroke patients for reperfusion therapies in delayed time windows has been and is being tested in clinical trials. However, whether the more available and cost-effective perfusion computed tomography (PCT) may be useful to select candidates for delayed intravenous thrombolysis remains largely unexplored. We aimed to evaluate the safety and efficacy of PCI-guided intravenous thrombolysis beyond 4.5 h after stroke onset. Methods: We prospectively studied all consecutive acute ischemic stroke patients treated with intravenous tissue plasminogen activator (tPA) in our stroke unit between January 2008 and December 2010. Patients treated within 0-4.5 h were treated according to non-contrast CI (NCCI) criteria. Beyond 4.5 h, patients received intravenous tPA according to PCT criteria, i.e. an infarct core on cerebral blood volume (CBV) maps not exceeding ore third of the middle cerebral artery (MCA) territory and tissue at risk as defined by mean transit time-CBV mismatch greater than 20%. Pre-determined primary endpoints were symptomatic hemorrhagic transformation and favorable long-term outcome, while early neurological improvement and MCA recanalization were considered secondary endpoints. Statistical analysis included bivariate comparisons between the two groups for each endpoint and logistic regression models when significance was found in bivariate analyses. This study was approved by our local ethics committee. Results: A total of 245 patients received intravenous thrombolysis. After the groups were matched by baseline National Institutes of Health Stroke Scale score, 172 patients treated at <4.5 hand 43 patients treated at >4.5 h were finally included. Early and late groups were comparable regarding baseline variables; only cardioembolic etiology was more frequent in the >4.5 h group. Rates of symptomatic hemorrhagic transformation (2.9% in the <4.5 h group vs. 2.3% in the >4.5 h group; p = 1.0) and good long-term outcome (64.5 vs. 60.5%, respectively; p = 0.620) were similar between the groups. However, delayed intravenous thrombolysis was independently associated with a worse early clinical course [odds ratio (OR) 2.07, 95% confidence interval (Cl) 1.04-4.1; p = 0.038] and lower 2-hour MCA recanalization rates (OR 0.4, 95% Cl 0.1 7-0.92; p = 0.03). Conclusion: Primary safety and efficacy endpoints were comparable between the early and delayed thrombolysis groups. The results of our exploratory study may justify a randomized clinical trial to test the safety and efficacy of PCT-guided intravenous thrombolysis in acute ischemic stroke patients presenting beyond 4.5 h from symptom onset. [ABSTRACT FROM AUTHOR]