Document Detail


Efficacy and safety of fasudil in patients with stable angina: a double-blind, placebo-controlled, phase 2 trial.
MedLine Citation:
PMID:  16286163     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVES: This study sought to evaluate the efficacy and safety of fasudil, an orally available rho kinase inhibitor, in patients with stable angina. BACKGROUND: Several small, non-placebo-controlled trials suggest that fasudil reduces myocardial ischemia in patients with stable or vasospastic angina. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors:
Ralph M Vicari; Bernard Chaitman; Deborah Keefe; William B Smith; Steven G Chrysant; Melvin J Tonkon; Neville Bittar; Robert J Weiss; Hugo Morales-Ballejo; Udho Thadani;
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Publication Detail:
Type:  Clinical Trial, Phase II; Journal Article; Multicenter Study; Randomized Controlled Trial; Research Support, Non-U.S. Gov't     Date:  2005-10-19
Journal Detail:
Title:  Journal of the American College of Cardiology     Volume:  46     ISSN:  1558-3597     ISO Abbreviation:  J. Am. Coll. Cardiol.     Publication Date:  2005 Nov 
Date Detail:
Created Date:  2005-11-15     Completed Date:  2005-12-29     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8301365     Medline TA:  J Am Coll Cardiol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1803-11     Citation Subset:  AIM; IM    
Affiliation:
MIMA Century Research Associates, Melbourne, Florida 32901, USA. ralph.vicari@mima.com
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MeSH Terms
Descriptor/Qualifier:
1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine / analogs & derivatives*,  therapeutic use
Aged
Angina Pectoris / drug therapy*
Double-Blind Method
Female
Humans
Male
Middle Aged
Chemical
Reg. No./Substance:
103745-39-7/fasudil; 84477-87-2/1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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