2022 年 39 巻 3 号 p. 367-372
Stroke patients with unknown time of onset have been previously excluded from intravenous thrombolysis. To determine whether intravenous alteplase is safe and effective in these patients, four randomized controlled trials were performed in the world ; WAKE–UP, EXTEND, ECASS 4, and our THAWS (Thrombolysis for Acute Wake–Up and Unclear–Onset Strokes With Alteplase at 0.6mg/kg). THAWS was an investigator–initiated, multicenter, randomized, open–label, blinded–endpoint trial. Patients met the standard indication criteria for intravenous thrombolysis other than a time last–known–well >4.5h (e.g., wake–up stroke). Patients were randomly assigned (1:1) to receive alteplase at 0.6mg/kg or standard medical treatment if MRI showed acute ischemic lesion on diffusion–weighted imaging and no marked corresponding hyperintensity on FLAIR (DWI–FLAIR mismatch). The primary outcome was a favorable outcome (90–day modified Rankin Scale score of 0–1). For 131 patients (55 women, age 74.4±12.2 years), favorable outcome was comparable between the alteplase group (47.1%) and the control group (48.3%, relative risk 0.97, 95% confidence interval 0.68–1.41). Symptomatic intracranial hemorrhage within 22–36h occurred in 1 patient and none, respectively. In a sub–analysis, favorable outcome was more common in the alteplase group than in the control group in patients with DWI–ASPECTS 5–8 (relative risk 4.75, 95% confidence interval 1.33–30.2) and tended to be more common in patients with core volume >6.4mL (6.15, 0.87–43.64). In a systematic review and meta–analysis of individual patient data of the above four trials, a favorable outcome was more common in the alteplase group than in the control group (47% vs. 39%, adjusted odds ratio 1.50, 95% confidence interval 1.10–2.04). In the current guidelines, intravenous thrombolysis is eligible for unknown onset stroke patients with a DWI–FLAIR or perfusion mismatch.
