Treatment With Tissue Plasminogen Activator in the Golden Hour and the Shape of the 4.5-Hour Time-Benefit Curve in the National United States Get With The Guidelines-Stroke Population

Abstract

Background: Earlier tissue plasminogen activator 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 patients who had acute ischemic stroke treated with intravenous tissue plasminogen activator within 4.5 hours of onset from the Get With The Guidelines-Stroke US national program. Onset-to-treatment 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 tissue plasminogen activator–treated patients, the median onset-to-treatment time was 141 minutes (interquartile range, 110–173) and 878 patients (1.3%) were treated within the first 60 minutes. Treatment within 60 minutes, compared with treatment within 61 to 270 minutes, was associated with increased odds of discharge to home (adjusted odds ratio, 1.25; 95% confidence interval, 1.07–1.45), independent ambulation at discharge (adjusted odds ratio, 1.22; 95% confidence interval, 1.03–1.45), and freedom from disability (modified Rankin Scale 0–1) at discharge (adjusted odds ratio, 1.72; 95% confidence interval, 1.21–2.46), without increased hemorrhagic complications or in-hospital mortality. The pace of decline in benefit of tissue plasminogen activator from onset-to-treatment 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 the 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.

Injection of Microporous Annealing Particle (MAP) Hydrogels in the Stroke Cavity Reduces Gliosis and Inflammation and Promotes NPC Migration to the Lesion

“…To date, intravenous thrombolysis and reperfusion therapies using intravenously administered recombinant tissue plasminogen activator (tPA) are the only effective therapies to treat stroke [3] . However, tPA is only effective during the first 4.5 hours after stroke onset, resulting in only about 5% of stroke patients benefiting from this treatment and leaving the majority of patients with long term disability [2, 4] . Besides physical therapy, there are no FDA approved therapies that promote recovery from the long-term disability caused by stroke, leaving an increasing number of patients with limited options [5] .…”

Alteplase for Acute Ischemic Stroke after Heparin Reversal with Protamine: A Case Report and Review

“…However, it is paramount to administer alteplase as quickly as possible, given that with further delays in alteplase administration the odds of a favorable 3month outcome decrease and the risk of ICH may increase. 2,[11][12][13][14] Our patient did not require ongoing therapeutic anticoagulation for stroke prevention in atrial fibrillation or for venous thromboembolism treatment. These situations introduce an additional layer of complexity given the underlying thrombotic disease states present, which was not necessarily the case with our patient.…”

“…Alteplase may be administered up to 4.5 hours after last known well time in patients not meeting exclusion criteria. However, it is paramount to administer alteplase as quickly as possible, given that with further delays in alteplase administration the odds of a favorable 3‐month outcome decrease and the risk of ICH may increase …”

“…Repeat aPTT was in the normal range, and thus alteplase was administered. Because delays in alteplase for AIS decrease the possibility of good functional outcome and increase the risk of hemorrhage, we decided not to delay alteplase by waiting for the aPTT to fall within normal range, despite the relatively short half‐life. The possibility exists that given the many patient‐specific factors associated with heparin elimination that our patient's aPTT would not have decreased to within normal limits within the treatment window.…”

Identifying Key Words in 9-1-1 Calls for Stroke: A Mixed Methods Approach

“…5 Accurate EMD and paramedic identification of stroke leads to high-priority dispatch of responding personnel, shorter on-scene time, quicker transport of patients to stroke center hospitals, and improved emergency department time metric quality measures for stroke 5–8. Timely stroke care is critical for patient outcomes, as every 15 minute delay to thrombolysis results in a 4% increase in poor outcomes and most patients become ineligible for any form of revascularization therapy six hours after symptom onset 3,4. Additionally, patients with acute ischemic stroke from large vessel occlusion benefit from timely mechanical thrombectomy, emphasizing the importance of prehospital identification of severe stroke and coordination of all members of a prehospital stroke system of care 1,9–15.…”