Intravenous Alteplase for Stroke of Unknown Onset Time: Confirmation of a Benefit

Acute ischemic stroke patients with an unknown time of symptom onset were excluded from the initial randomized trials of intravenous thrombolysis for stroke. So, when patients present with stroke symptoms upon waking or with an unwitnessed time of symptom onset and inability to convey when the symptoms started, the role of thrombolysis is less certain. Recent trials have evaluated the potential role of imaging biomarkers (mismatch on MRI with diffusion-weighted imaging–fluid-attenuated inversion recovery or perfusion imaging) to select patients with unknown stroke onset time for thrombolysis, but some analyses have been limited by small samples sizes and low statistical power. Therefore, a consortium of investigators conducted a systematic review and meta-analysis of individual patient-level data, evaluating the safety and efficacy of stroke thrombolysis based on imaging biomarkers when the time of symptom onset is unknown.

Four trials with a total of 843 patients were included in this analysis: WAKE-UP, EXTEND, THAWS, and ECASS-4. The prespecified primary outcome (modified Rankin Scale [mRS] score ≤1 at 90 days) and secondary efficacy outcomes (shift to lower mRS scores; mRS ≤2 at 90 days) favored the pooled alteplase group over the control group. As for safety outcomes, death at 90 days and symptomatic intracranial hemorrhage were each more common with alteplase, but the proportion of patients with dependence or death (mRS score 3–6) was significantly lower in the alteplase group than the control group (35% vs. 42%).