Effects of fasudil in acute ischemic stroke: Results of a prospective placebo-controlled double-blind trial

Background: A multicenter, double-blind, placebo-controlled study was conducted to assess the efficacy and safety of fasudil, a Rhokinase inhibitor (RKI), in the treatment of acute ischemic stroke. Methods: A total of 160 patients, who were able to receive drug treatment within 48 h of acute ischemic stroke onset were enrolled. Patients received either 60 mg fasudil or a placebo (saline) by intravenous injection over 60 min, twice daily for 14 days. The primary end points were neurological status at 2 weeks after the start of treatment, and clinical outcome at I month after the onset of symptoms. Results: Fasudil treatment resulted in significantly greater improvements in both neurological functions (p = 0.0013), and clinical outcome (p = 0.0015). There were no serious adverse events reported in the fasudil group. The average trough value (12 h values) of active metabolite hydroxyfasudil, another RKI, in healthy elderly volunteers receiving 60 mg of fasudil was 0.077 mu M-a concentration well above that needed to inhibit Rho-kinase (0.025-0.05 mu M). Conclusion: Treatment with fasudil-within 48 h of acute ischemic stroke onset significantly improved the patient's clinical outcome. This study found fasudil to be a useful and safe drug for patients with acute ischemic stroke. Further evaluations, for example, 3-month functional outcomes in a larger clinical trial, may help to define the efficacy of fasudil in acute ischemic stroke. (c) 2005 Elsevier B.V All rights reserved.