Expanded Indication for Recombinant Tissue Plasminogen Activator from 3 to 4.5 h after Onset of Stroke in Japan

We examined the impact of expansion of the time window (from 3 to 4.5 hours) in the labeled indication for recombinant tissue-plasminogen activator (rt-PA) in August 2012 on the use of rt-PA for patients with acute ischemic stroke (AIS) and the outcomes of patients treated with rt-PA.

Using a Japanese nationwide inpatient claims database, we identified patients with AIS who admitted to hospitals that consecutively participated in the database from 2010 to 2014. We defined the pre-expansion period as before August 2012 and the post-expansion period as after August 2012. We conducted an interrupted time-series analysis using patient-level data to examine the association between the expansion and use of rt-PA. We also assessed the association of the expansion with outcomes in patients treated with rt-PA.

Among 257,778 patients with AIS, 4.5% patients (5,796/129,326) were treated with rt-PA in the pre-expansion period and 5.8% patients (7,483/128,452) were treated with rt-PA in the post-expansion period. The expansion was associated with greater use of rt-PA (adjusted odds ratio [aOR], 1.35; 95% confidence interval [CI], 1.24-1.48). Among patients treated with rt-PA, the expansion was associated with functional independence (modified Rankin scale of ≤2) at discharge (aOR, 1.26; 95% CI, 1.03-1.54), but not with in-hospital mortality (aOR, 0.92; 95% CI, 0.68-1.24).

This study showed that expansion of the time window for rt-PA was associated with increased use of rt-PA in patients with AIS, while the functional outcome at discharge was improved after the expansion in patients treated with rt-PA.