Another Enchantment From ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study)

> It is a capital mistake to theorise before one has data. Insensibly one begins to twist facts to suit theories, instead of theories to suit facts. > > —Sir Arthur Ignatius Conan Doyle, 1892, The Adventures of Sherlock Holmes , Sherlock Holmes in "A Scandal in Bohemia"See related article, p 1877Ongoing discussions address the optimum dose of r-tPA (recombinant tissue plasminogen activator). Although in most countries in the world, the so-called standard dose of 0.9 mg/kg bodyweight is approved and used (based on numerous randomized controlled trials and joint and meta-analyses), in Japan and some other Asian countries, a low dose of 0.6 mg/kg bodyweight has been proposed or approved. Besides cost issues, the original rationale for the low dose was derived from the fear that Asians are a more bleeding-prone ethnic group and was tested because of safety concerns. On the contrary, the value of having 1 drug at 1 dose for an emergency situation is helpful because it is still a challenge to establish only that worldwide.After a single-arm nonrandomized study in 103 patients in J-ACT 11 (Japan Alteplase Clinical Trial), the dose of 0.6 mg/kg was approved in Japan. Efficacy and safety of this lower-dose thrombolytic therapy were confirmed by postmarketing surveys and registries in Japan, that is, J-ACT 22 (58 patients), J-MARS (Japan Postmarketing Alteplase Registration Study3; 7492 patients; 4944 with 3-month outcomes), and SAMURAI (Stroke Acute Management With Urgent Risk-Factor, Assessment Improvement Study)4 (600 patients). All these nonrandomized studies suggested with a low data quality (because of trial design) that intravenous thrombolysis with a 0.6 mg/kg dose achieved numerically similar outcomes and safety end points as comparable data sets from the large randomized controlled clinical trials.There is nothing like first hand evidence.5 About 1 year ago, Anderson …