Treatment with TPA in the "Golden Hour" and the Shape of the 4.5 Hour Time-Benefit Curve in the National US Get With The Guidelines-Stroke Population
Background—Earlier tissue plasminogen activator (tPA) treatment improves ischemic stroke outcome, but aspects of the time-benefit relationship still not well delineated are: 1) the degree of additional benefit accrued with treatment in the first 60 minutes after onset, and 2) the shape of the time-benefit curve through 4.5 hours.
Methods—We analyzed acute ischemic stroke patients treated with intravenous tPA within 4.5 hours of onset from the Get With The Guidelines-Stroke US national program. Onset to treatment (OTT) time was analyzed as a continuous, potentially nonlinear variable and as a categorical variable comparing patients treated within 60 minutes of onset with later epochs.
Results—Among 65,384 tPA-treated patients, the median OTT was 141 minutes (IQR 110-173) and 878 patients (1.3%) were treated within the first 60 minutes. Treatment within 60 minutes, compared with treatment within 61-270 minutes, was associated with increased odds of discharge to home (adjusted OR 1.25, 95% confidence intervals [CI] 1.07-1.45), independent ambulation at discharge (adjusted OR 1.22, 95% CI 1.03-1.45), and freedom from disability (modified Rankin Scale 0-1) at discharge (adjusted OR 1.72, 95% CI 1.21-2.46), without increased hemorrhagic complications or in-hospital mortality. The pace of decline in benefit of tPA from OTT times of 20 through 270 minutes was mildly nonlinear for discharge to home, with more rapid benefit loss in the first 170 minutes than later, and linear for independent ambulation and in-hospital mortality.
Conclusions—Thrombolysis started within the first 60 minutes after onset is associated with best outcomes for patients with acute ischemic stroke, and benefit declined more rapidly early after onset for ability to be discharged home. These findings support intensive efforts to organize stroke systems of care to improve the timeliness of thrombolytic therapy in acute ischemic stroke.
- Golden hour thrombolysis
- time-benefit curve
- acute ischemic stroke
- tissue-type plasminogen activator
- Received May 6, 2016.
- Revision received July 14, 2016.
- Accepted September 20, 2016.