Recombinant Tissue-Type Plasminogen Activator (Alteplase) for Ischemic Stroke

THE FOOD AND DRUG ADMINIStration (FDA) approval in June 1996 of intravenous recombinant tissue-type plasminogen activator (rt-PA) for patients with acute ischemic stroke treated within 3 hours of symptom onset marked a historic first step in treating this devastating disease. This approval was primarily based on the results of the National Institute of Neurologic Disorders (NINDS) trials (1 and 2). In the NINDS trials, patients with ischemic stroke were treated within 3 hours of symptom onset with either 0.9 mg/kg of rt-PA (alteplase) (maximum dose ,90 mg) or placebo. A significant 11% to 15% absolute benefit was found favoring rt-PA despite a significant increase in the symptomatic intracerebral hemorrhage (ICH) rate (6.4% vs 0.6%; P,.001) at 36 hours. The current approved use of rt-PA is limited to otherwise eligible patients in whom treatment can be initiated within 3 hours after the onset of stroke symptoms. This greatly restricts the number of patients who could potentially be treated, because most stroke patients present more than 3 hours after sympAuthor Affiliations: Oregon Stroke Center, Portland (Dr Clark); Stucky Research Center, Fort Wayne, Ind (Dr Wissman); Stanford Stroke Center, Stanford University, Palo Alto, Calif (Dr Albers); Department of Neurology, University of Alberta, Edmonton (Dr Jhamandas); Marshfield Clinic, Marshfield, Wis (Dr Madden); and Genentech Inc, South San Francisco, Calif (Dr Hamilton). A complete list of the ATLANTIS Study Investigators appears at the end of this article. †Deceased. Corresponding Author and Reprints: Wayne M. Clark, MD, Oregon Stroke Center, UHS 44, Oregon Health Sciences University, 3181 SW Sam Jackson Park Rd, Portland, OR 97201 (e-mail:[email protected]). Context Recombinant tissue-type plasminogen activator (rt-PA) improves outcomes for patients with acute ischemic stroke, but current approved use is limited to within 3 hours of symptom onset. This restricts the number of patients who can be treated, since most stroke patients present more than 3 hours after symptom onset.