Intravenous thrombolytic therapy for stroke: A review of recent studies and controversies

Study objectives: To review the randomized, controlled, multicenter trials of intravenous thrombolytic therapy for ischemic stroke. Methods: Studies of ischemic stroke confirmed by computed tomography (CT) a nd randomization of more than 100 patients are reviewed. Streptokinase stud ies are the MAST-I, the MAST-E, and the ASK Trial. Studies using tissue pla sminogen activator (tPA) are the NINDS Stroke Study, ECASS I, ECASS II, and ATLANTIS. One study using ancrod is STAT. We discuss significant factors c ommon to each study, including thrombolytic agent used, CT scan interpretat ion, time of therapy administration in relation to stroke onset, thrombolyt ic dose, ancillary medication administration, safety, and neurologic outcom es. Results: All streptokinase studies were stopped early because of increased mortality in the treated groups. Initial results of the STAT study are prom ising; publication of full study details is awaited. The ATLANTIS study was terminated early because of nonstatistical efficacy at interim analysis. T he NINDS and the ECASS trials were completed; only the NINDS study demonstr ated significant increase in the percentage of patients with complete recov ery or minimal deficit at 3 months, without significant difference in morta lity in the treated group. Conclusion: This review supports the use of intravenous thrombolytic therap y for ischemic stroke using tPA at a dose of .9 mg/kg body weight and a "go lden window" treatment time of 3 hours. Administration without strict adher ence to protocol, even within this time frame, may shift the benefit/risk p rofile of tPA. We recommend the treating physician have rapid access to CT scanning and to collaboration with individuals experienced in the evaluatio n of stroke and CT interpretation.