Publication Date: June 2019 (Volume 21, Supplement 6)
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Stroke is the fifth leading cause of death in the United States and an important cause of long-term disability.1 Approximately 795,000 people suffer from stroke each year (610,000 primary strokes and 185,000 recurrent strokes),1 with ischemic stroke representing the vast majority of all stroke types (87%).2 The cornerstone of acute ischemic stroke treatment relies on rapid clearance of an offending thrombus in the cerebrovascular system.3 Advanced neuroimaging and clinical trials, together with continuous adjustments of inclusion/exclusion criteria, have helped emergency clinicians to rapidly and more accurately identify the patients who will benefit from acute stroke treatment.
Excerpt From This Issue
Alteplase (recombinant tissue plasminogen activator [rt-PA]) was the first drug approved by the United States Food and Drug Administration (FDA) for treatment of acute ischemic stroke. rt-PA is a protease derived by recombinant DNA technology that activates fibrin-bound plasminogen, leading to plasmin formation and the disintegration of fibrin clots.4,5 In 1995, the National Institute of Neurological Disorders and Stroke (NINDS) Recombinant Tissue Plasminogen Activator trial showed that patients suffering from ischemic stroke who received intravenous (IV) rt-PA in a dose of 0.9 mg/kg within 3 hours of symptom onset had a more favorable outcome at 3 months than those who received placebo (odds ratio [OR] 1.7; 95% confidence interval [CI], 1.2 to 2.6; P = .008).6 Since then, other studies and randomized controlled trials have confirmed the safety and efficacy of IV thrombolysis (IVT).7-12
In 2008, the ECASS III study13 showed a statistically significant benefit in selected patients treated with IV rt-PA between 3 hours and 4.5 hours from symptom onset. Additional studies have supported the use of IVT in a time window as late as 4.5 hours after symptom onset.14-16 The IST-3 trial attempted to extend the time window for IVT administration beyond the 4.5-hour time window, but was unable to show a meaningful improvement in outcome beyond that time point.17 However, the recently published EXTEND trial reveals promising results for extending the time window up to 9 hours, in selected populations.18 The benefit of IVT in favorable neurologic outcome has been demonstrated to persist at both 3 and 12 months after stroke occurrence.6,19