IV Thrombolysis in Unknown-Onset Stroke

Study Questions:

What is the safety and efficacy of intravenous (IV) alteplase in ischemic stroke patients with unknown onset (UKO) of symptoms compared with those treated within 4.5 hours in a large cohort?


The investigators analyzed data from 47,237 patients with acute ischemic stroke receiving IV tissue-type plasminogen activator (alteplase) in hospitals participating in the Safe Implementation of Treatment in Stroke-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 hemorrhage (SICH) per Safe Implementation of Treatment in Stroke on the 22-36 hours post-treatment neuroimaging and mortality, and functional outcome assessed by the modified Rankin Scale at 3 months. Logistic regression was used to study the adjusted probability of SICH, functional independency, and mortality between groups.


Patients in the UKO group were significantly older, had more severe stroke at baseline, and longer door-to-needle times than patients in the ≤4.5 hours group. Logistic regression showed similar risk of SICH (adjusted odds ratio [OR], 1.09; 95% confidence interval [CI], 0.44–2.67) and no significant differences in functional independency (modified Rankin Scale score of 0–2; adjusted OR, 0.79; 95% CI, 0.56–1.10), but higher mortality (adjusted OR, 1.58; 95% CI, 1.04–2.41) in the UKO group compared with the ≤4.5 hours group. Patients treated within 4.5 hours showed reduced disability over the entire range of modified Rankin Scale compared with the UKO group (common adjusted OR, 1.29; 95% CI, 1.01–1.65).


The authors concluded that there is no excess risk of SICH, but there is increased mortality and less favorable outcome in patients with UKO stroke compared with patients treated within the approved time window.


This study reports that in stroke patients with UKO treated with systemic thrombolysis, the occurrence of SICH was comparable to patients treated within 4.5 hours of symptoms onset, but mortality and functional disability over the entire range of the modified Rankin Scale were higher. At this time, routine treatment with IV alteplase in stroke patients with unknown time of symptom’s onset is not recommended. Additional studies are indicated to define optimal strategies to manage stroke patients with unknown time of symptom’s onset.

Clinical Topics: Anticoagulation Management, Dyslipidemia, Lipid Metabolism

Keywords: Anticoagulants, Cerebral Hemorrhage, Mortality, Neuroimaging, Outcome Assessment (Health Care), Risk Management, Stroke, Thrombolytic Therapy, Tissue Plasminogen Activator, Vascular Diseases

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