Background and Purpose: Unknown onset (UKO) stroke patients are at present excluded from thrombolytic therapy thrombolysis according to approval criteria and guideline recommendations. However, a number of them might benefit from the treatment. We aim to study the safety and efficacy of intravenous (IV) tissue plasminogen activator (tPA) in ischemic stroke patients with UKO of symptoms compared to those treated within 4.5 hours in a large cohort.
Methods: Data were analyzed from 47,237 patients with acute ischemic stroke receiving IV-tPA in hospitals participating in the SITS International Stroke Thrombolysis Registry between 2010 and 2014. Two groups were defined: 1) patients with UKO, (n=502) and 2) patients treated within 4.5 hours of stroke onset, (n=44,875). Outcome measures were symptomatic intracerebral haemorrhage (SICH)-SITS, mortality at 3 months and functional independency as a score in the modified Rankin Scale (mRS) of 0-2 at 3 months.
Results: Patients in UKO group were older (74 [65-82] vs. 72 [62-79] years, p<0.001), and had more severe stroke at baseline as measured by NIH Stroke Scale (12 [7-18] vs. 11 [6-17], p<0.001) than ≤4.5h. SICH-SITS occurred in 2.7% vs. 1.6% (p=0.052). At 3 months, mortality was higher (22%vs.16.9%, p=0.01) and functional independency was lower (46.8% vs. 56.2%, p<0.001) in the UKO group than ≤4.5h. In the multivariate analysis, these differences disappeared after adjustment baseline imbalances; SICH-SITS (OR0.98; 95% CI [0.43-2.21], p=0.962), mortality (OR0.88; 95% CI [0.64-1.20], p=0.435) and functional independency (OR 0.71; 95% CI [0.48-1.04], p=0.083).
Conclusions: Our data suggest no excess risk of SICH in patients with UKO stroke treated with tPA and similar rate of functional independency and mortality than patients treated within 4.5 hours.