Efficacy and safety of fasudil in patients with stable angina

A double-blind, placebo-controlled, phase 2 trial

Ralph M. Vicari, Bernard Chaitman, Deborah Keefe, William Smith, Steven G. Chrysant, Melvin J. Tonkon, Neville Bittar, Robert J. Weiss, Hugo Morales-Ballejo, Udho Thadani

Research output: Contribution to journalArticle

148 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1803-1811
Number of pages9
JournalJournal of the American College of Cardiology
Volume46
Issue number10
DOIs
StatePublished - Nov 15 2005

Fingerprint

Stable Angina
Placebos
Safety
Exercise
rho-Associated Kinases
Nitroglycerin
Calcium Channel Blockers
Myocardial Ischemia
fasudil
Randomized Controlled Trials

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine

Cite this

Efficacy and safety of fasudil in patients with stable angina : A double-blind, placebo-controlled, phase 2 trial. / Vicari, Ralph M.; Chaitman, Bernard; Keefe, Deborah; Smith, William; Chrysant, Steven G.; Tonkon, Melvin J.; Bittar, Neville; Weiss, Robert J.; Morales-Ballejo, Hugo; Thadani, Udho.

In: Journal of the American College of Cardiology, Vol. 46, No. 10, 15.11.2005, p. 1803-1811.

Research output: Contribution to journalArticle

Vicari, RM, Chaitman, B, Keefe, D, Smith, W, Chrysant, SG, Tonkon, MJ, Bittar, N, Weiss, RJ, Morales-Ballejo, H & Thadani, U 2005, 'Efficacy and safety of fasudil in patients with stable angina: A double-blind, placebo-controlled, phase 2 trial', Journal of the American College of Cardiology, vol. 46, no. 10, pp. 1803-1811. https://doi.org/10.1016/j.jacc.2005.07.047
Vicari, Ralph M. ; Chaitman, Bernard ; Keefe, Deborah ; Smith, William ; Chrysant, Steven G. ; Tonkon, Melvin J. ; Bittar, Neville ; Weiss, Robert J. ; Morales-Ballejo, Hugo ; Thadani, Udho. / Efficacy and safety of fasudil in patients with stable angina : A double-blind, placebo-controlled, phase 2 trial. In: Journal of the American College of Cardiology. 2005 ; Vol. 46, No. 10. pp. 1803-1811.
@article{dcd8270034254af2a99598874f1590ad,
title = "Efficacy and safety of fasudil in patients with stable angina: A double-blind, placebo-controlled, phase 2 trial",
abstract = "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.",
author = "Vicari, {Ralph M.} and Bernard Chaitman and Deborah Keefe and William Smith and Chrysant, {Steven G.} and Tonkon, {Melvin J.} and Neville Bittar and Weiss, {Robert J.} and Hugo Morales-Ballejo and Udho Thadani",
year = "2005",
month = "11",
day = "15",
doi = "10.1016/j.jacc.2005.07.047",
language = "English (US)",
volume = "46",
pages = "1803--1811",
journal = "Journal of the American College of Cardiology",
issn = "0735-1097",
publisher = "Elsevier USA",
number = "10",

}

TY - JOUR

T1 - Efficacy and safety of fasudil in patients with stable angina

T2 - A double-blind, placebo-controlled, phase 2 trial

AU - Vicari, Ralph M.

AU - Chaitman, Bernard

AU - Keefe, Deborah

AU - Smith, William

AU - Chrysant, Steven G.

AU - Tonkon, Melvin J.

AU - Bittar, Neville

AU - Weiss, Robert J.

AU - Morales-Ballejo, Hugo

AU - Thadani, Udho

PY - 2005/11/15

Y1 - 2005/11/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=27644449718&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=27644449718&partnerID=8YFLogxK

U2 - 10.1016/j.jacc.2005.07.047

DO - 10.1016/j.jacc.2005.07.047

M3 - Article

VL - 46

SP - 1803

EP - 1811

JO - Journal of the American College of Cardiology

JF - Journal of the American College of Cardiology

SN - 0735-1097

IS - 10

ER -