Safety Of Fasudil Research Articles

P793Usefulness and safety of fasudil, a selective Rho-kinase inhibitor, for PCI-related myocardial ischemia in interventional cardiology

P793Usefulness and safety of fasudil, a selective Rho-kinase inhibitor, for PCI-related myocardial ischemia in interventional cardiology

Systematic assessment and meta-analysis of the efficacy and safety of fasudil in the treatment of cerebral vasospasm in patients with subarachnoid hemorrhage

Cerebral vasospasm (CVS) is a frequent and unpredictable complication in patients with subarachnoid hemorrhage (SAH) and often leads to poor outcomes. This study was aimed at evaluating the efficacy and safety of fasudil in the treatment of CVS in patients with SAH. A search was conducted using the full-text database of Chinese scientific journals, the Wanfang Database (January 1999 to November 2010), the Chinese Medical Association Digital Journal Database, PubMed, the Cochrane library, OVID, and EMBase (searching through November 2010). A total of 8 studies met the inclusion criteria. The incidence rates of symptomatic CVS and CVS confirmed by angiography among the patients in the fasudil group were only 48% (odds ratio [OR] = 0.48, 95% confidence interval [CI]: 0.32-0.72, P = 0.0005) and 40% (OR = 0.40, 95% CI: 0.24-0-67, P = 0.0004) respectively of that of the control group. The odds ratios of cerebral infarction for all cases and cerebral infarction for CVS cases in the fasudil group were only 50% (OR = 0.50, 95% CI: 0.34-0.76, P = 0.0009) and 43% (OR = 0.43, 95% CI: 0.26-0.70, P = 0.0008) respectively of that of the control group. Fasudil greatly reduces the occurrence of CVS and cerebral infarction in SAH patients, significantly improves the clinical outcomes of the patients (as assessed by the Glasgow Outcome Scale). Because of the limited number of trials and samples available for analysis, the conclusions from the present study still need to be validated with results from large randomized, controlled clinical trials.

Efficacy and Safety of Fasudil in Patients With Subarachnoid Hemorrhage: Final Results of a Randomized Trial of Fasudil Versus Nimodipine

Fasudil is believed to be at least equally effective as nimodipine for the prevention of cerebral vasospasm and subsequent ischemic injury in patients undergoing surgery for subarachnoid hemorrhage (SAH). We report the final results of a randomized, open trial to compare the efficacy and safety of fasudil with nimodipine. A total of 63 patients undergoing surgery for SAH received fasudil and 66 received nimodipine between 1998 and 2004. Symptomatic vasospasm, low density areas on computed tomography (CT), clinical outcomes, and adverse events were all recorded, and the results were compared between the fasudil and nimodipine groups. Absence of symptomatic vasospasm, occurrence of low density areas associated with vasospasm on CT, and occurrence of adverse events were similar between the two groups. The clinical outcomes were more favorable in the fasudil group than in the nimodipine group (p = 0.040). The proportion of patients with good clinical outcome was 74.5% (41/55) in the fasudil group and 61.7% (37/60) in the nimodipine group. There were no serious adverse events reported in the fasudil group. The present results suggest that fasudil is equally or more effective than nimodipine for the prevention of cerebral vasospasm and subsequent ischemic injury in patients undergoing surgery for SAH.

Efficacy and Safety of Fasudil in Patients With Stable Angina: A Double-Blind, Placebo-Controlled, Phase 2 Trial

Efficacy and Safety of Fasudil in Patients With Stable Angina: A Double-Blind, Placebo-Controlled, Phase 2 Trial

Efficacy and Safety of Fasudil in Patients With Stable Angina: A Double-Blind, Placebo-Controlled, Phase 2 Trial

This study sought to evaluate the efficacy and safety of fasudil, an orally available rho kinase inhibitor, in patients with stable angina. Several small, non-placebo-controlled trials suggest that fasudil reduces myocardial ischemia in patients with stable or vasospastic angina. In a multicenter, double-blind, placebo-controlled, randomized trial, the efficacy and safety of fasudil were evaluated in stable angina patients. Of the 206 patients screened, 84 patients with reproducible exercise times were randomized 1:1 to fasudil or placebo. Nitroglycerin as needed and a beta- or calcium-channel blocker were allowed. Fasudil or matching placebo was force-titrated from 20 mg three times daily to 80 mg twice daily with 20 mg twice-daily increments every two weeks. Symptom-limited exercise testing was performed after two, four, six, and eight weeks of treatment. At peak, exercise duration was significantly improved at all visits in both groups, although exercise duration was numerically greater in patients receiving fasudil versus those receiving placebo. Time to > or =1 mm ST-segment depression was increased with fasudil at both peak and trough compared with placebo (172.1 s vs. 44.0 s, p = 0.001, and 92.8 s vs. 26.4 s, p = 0.02, respectively). Fasudil improved Seattle Angina Questionnaire scores. No significant differences in Canadian Cardiovascular Society class, time to angina, or frequency of angina or nitroglycerin use were noted between groups. Fasudil did not affect heart rate or blood pressure, and was well tolerated. Fasudil up to 80 mg three times daily significantly increased the ischemic threshold of angina patients during exercise with a trend toward increased exercise duration. Further investigation of fasudil doses >80 mg three times daily is indicated.

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 Rho-kinase 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 1 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 μM—a concentration well above that needed to inhibit Rho-kinase (0.025–0.05 μM). 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.

1023-96 A randomized double-blind placebo-controlled phase 2 study on the efficacy and safety of fasudil in patients with stable angina

1023-96 A randomized double-blind placebo-controlled phase 2 study on the efficacy and safety of fasudil in patients with stable angina