Safety and efficacy of 0.6 mg/kg rt-PA: optimum rt-PA dose revisited

• Published in: Annals of the New York Academy of Sciences 2012-09, Vol.1268 (1), p.108-112
• Main Author: Mori, Etsuro
• Format: Article
• Language: English
• Subjects: acute ischemic stroke; alteplase; Asian; Asian Continental Ancestry Group; Brain Ischemia - drug therapy; Brain Ischemia - ethnology; Cerebral Hemorrhage - chemically induced; Cerebral Hemorrhage - prevention & control; Clinical trials; Clinical Trials, Phase II as Topic - statistics & numerical data; Cohort Studies; Dosage; Dose-Response Relationship, Drug; Double-Blind Method; Effectiveness; Extrapolation; Follow-Up Studies; Humans; Japan - ethnology; Magnetic Resonance Angiography; Medical research; Meta-Analysis as Topic; Multicenter Studies as Topic - statistics & numerical data; Occlusion; Optimization; optimum dose; Prospective Studies; Randomized Controlled Trials as Topic - statistics & numerical data; Recombinant Proteins - administration & dosage; Recombinant Proteins - adverse effects; Recombinant Proteins - therapeutic use; recombinant tissue plasminogen activator; Safety; thrombolytic therapy; Tissue Plasminogen Activator - administration & dosage; Tissue Plasminogen Activator - adverse effects; Tissue Plasminogen Activator - therapeutic use
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1111/j.1749-6632.2012.06689.x

Although the internationally recommended dosage of alteplase, a single‐chain rt‐PA, is 0.9 mg/kg, 0.6 mg/kg is the only approved dosage in Japan, and it is widely used there. Duteplase is a two‐chain rt‐PA, and based on findings of the duteplase trials in the early 1990s, the smaller dosage of 0.6 mg/kg of alteplase was tested in the Japan Alteplase Clinical Trial (J‐ACT), which indicated that the efficacy/safety profile of this dose was comparable to the 0.9 mg/kg dosage used in other countries. The Japan Alteplase Clinical Trial II (J‐ACT II) further demonstrated efficacy of 0.6 mg/kg alteplase with regard to vascular outcomes in patients with middle cerebral artery (MCA) occlusion. Finally, the Japan post‐Marketing Alteplase Registration Study (J‐MARS) confirmed the efficacy/safety profile of 0.6 mg/kg alteplase in a clinical setting that was comparable to the dose of 0.9 mg/kg in the European counterpart, the Safe Implementation of Thrombolysis in Stroke‐Monitoring Study (SITS‐MOST). The dose of 0.6 mg/kg seems to be optimal, at least in far‐east Asians, and might be extrapolated to other ethnic groups as well.