Safety and Efficacy of Intravenous Tissue Plasminogen Activator Stroke Treatment in the 3- to 6-Hour Window Using Multimodal Transcranial Doppler/MRI Selection Protocol

Abstract

Background— Growing data point toward intravenous tissue plasminogen activator (tPA) benefit after 3 hours in selected stroke patients. We aim to study safety and efficacy of tPA treatment in the 3- to 6-hour window using multimodal transcranial Doppler (TCD)/MRI selection criteria. Methods— We studied patients with acute middle cerebral artery (MCA) occlusion. Patients within 0 to 3 hours from symptom onset (A) were treated according to standard computed tomography criteria. Treatment within 3 to 6 hours (B) was decided according to TCD/MRI protocol. Continuous TCD assessed clot location and recanalization. National Institutes of Health Stroke Scale (NIHSS) at 24 hours assessed neurological improvement/worsening and modified Rankin score <3 functional independence at third month. Results— Of 135 patients, 56 were in the 3- to 6-hour window. Only 13 (23%) patients within 3 to 6 hours did not meet MRI inclusion criteria. Finally, 122 patients were treated with tPA: A, 79 (65%); B, 43 (35%). Median time to treatment was: A, 136 minutes (range 60 to 180); B, 223 (185 to 360). There were no differences in demographic parameters, baseline NIHSS (A, 17; B, 17; P =0.89), and occlusion location (proximal MCA A, 65.8%; B, 74.4%; P =0.28). Recanalization rates at 2 hours were similar (A, 49.3%; B, 55.2%; P =0.33), as were hemorrhagic transformation rates (asymptomatic: A, 18.7%, B, 26.6%, P =0.43; symptomatic: A, 3.75%, B, 2.38%, P =0.66). Improvement at discharge was similar in both groups (NIHSS dropped 6.3 points [A] versus 6.1 [B]; P =0.86). However, the number of patients who benefited from treatment was slightly higher in the 3- to 6-hour group (A, 58.2%; B, 76.2%; P =0.05), whereas the same rate of patients worsened (A, 11.4%; B, 7.1%; P =0.46). At 3 months, the rate of independent patients was: A, 42% versus B, 38% ( P =0.74). Conclusions— tPA treatment can be safely and effectively extended to the 3- to 6-hour window using TCD/MRI selection criteria. Not using these criteria in the 3- to 6-hour window avoids potentially effective treatment in a high rate of patients.