CLINICAL RESEARCH: CLINICAL TRIAL
Efficacy and Safety of Fasudil in Patients With Stable Angina
A Double-Blind, Placebo-Controlled, Phase 2 Trial
Ralph M. Vicari, MD, FACC*,*,
Bernard Chaitman, MD, FACC ,
Deborah Keefe, MD, MPH, FACC ,
William B. Smith, MD, FACC ,
Steven G. Chrysant, MD, PhD, FACC||,
Melvin J. Tonkon, MD, FACC¶,
Neville Bittar, MD, FACC#,
Robert J. Weiss, MD, FACC**,
Hugo Morales-Ballejo, MD, FACC,
Udho Thadani, MBBS, MRCP, FRCPC, FACC for the Fasudil Study Group
* MIMA Century Research Associates, Melbourne, Florida
St. Louis University, St. Louis, Missouri
Berlex, Inc., Montville, New Jersey
New Orleans Center for Clinical Research, New Orleans, Louisiana
|| Oklahoma Cardiovascular and Hypertension Center, Oklahoma City, Oklahoma
¶ Apex Research Institute, Santa Ana, California
# Gemini Scientific, Madison, Wisconsin
** Androscoggin Cardiology Associates, Auburn, Maine
VA Medical Center, University of Oklahoma Health Science Center, Oklahoma City, Oklahoma
Manuscript received April 8, 2005;
revised manuscript received May 25, 2005,
accepted July 11, 2005.
* Reprint requests and correspondence: Dr. Ralph M. Vicari, MIMA Century Research Associates, 200 East Sheridan Road, Melbourne, Florida 32901. (Email: ralph.vicari{at}mima.com).
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  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.
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Abbreviations and Acronyms
| | CCS = Canadian Cardiovascular Society | | ECG = electrocardiogram | | ETT = exercise treadmill testing | | MRLC = myosin regulatory light chain | | SAQ = Seattle Angina Questionnaire |
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