Two studies using large databases provide details on timing and outcomes.

Clinical trials of thrombolysis for acute ischemic stroke typically have included fewer than 1000 patients. Two new studies involved larger datasets, allowing investigators to analyze important clinical issues in greater detail.

Saver and colleagues analyzed data from the national Get With The Guidelines–Stroke (GWTG-Stroke) database on 58,353 patients (median age, 72; 50.3% women) treated with tissue plasminogen activator (TPA) within 4.5 hours of symptom onset over a 9-year period. The median time from symptom onset to TPA administration was 144 minutes. Factors associated with earlier treatment included greater stroke severity, arrival by ambulance, and arrival during regular hours. Intracranial hemorrhage occurred in 4.9% of patients; 38.6% were discharged home. Earlier treatment, measured in 15-minute increments, was associated significantly with reduced mortality (odds ratio, 0.96), reduced intracranial hemorrhage (OR, 0.96), increased chance of independent ambulation at discharge (OR, 1.04), and increased rate of discharge to home (OR, 1.03).

The IST-3 collaborative group examined the effects of thrombolysis on 18-month quality-of-life and functional outcomes. Among more than 2300 patients from 10 countries who were randomized to usual care or thrombolysis within 6 hours of stroke, the adjusted odds of being alive and independent at 18 months were 28% greater with thrombolysis. Survival at 18 months did not differ. On a scale measuring mobility, self care, activity, pain, and anxiety, patient or caregiver reports of wellbeing improved significantly more between 6 and 18 months after stroke, and were better at 18 months, in the thrombolysis group, although anxiety was not lower.

COMMENT

The data from the large GWTG-Stroke database emphasize the importance of timely intervention for acute ischemic stroke. Currently, fewer than one third of patients are treated with thrombolysis with a door-to-needle time of <60 minutes (Stroke 2011; 42:2983). The Target: Stroke initiative of the American Heart Association/American Stroke Association aims to improve this rate to 50% in the next few years. Accelerating the pace of treatment will have multiple important benefits, including lower mortality and improved functional outcomes.

The study from the IST-3 investigators shows long-term benefits for functional status with prior thrombolytic therapy. Although multiple factors can affect health status 18 months after stroke (such as cardiac issues and infectious complications), the persisting improvements in functional status with prior thrombolytic therapy are reassuring.