Intracoronary basic fibroblast growth factor (FGF-2) in patients with severe ischemic heart disease: Results of a Phase I open-label dose escalation study

Roger J. Laham, Nicholas A. Chronos, Marilyn Pike, Mark E. Leimbach, James E. Udelson, Justin D. Pearlman, Roderic I. Pettigrew, M. J. Whitehouse, Carl Yoshizawa, Michael Simons

Research output: Contribution to journalArticle

193 Scopus citations

Abstract

OBJECTIVES: Evaluate the safety, tolerability and preliminary efficacy of intracoronary (IC) basic fibroblast growth factor (bFGF, FGF-2). BACKGROUND: FGF-2 is a heparin-binding growth factor capable of inducing functionally significant angiogenesis in animal models of myocardial ischemia. METHODS: Phase I, open-label dose-escalation study of FGF-2 administered as a single 20-min infusion in patients with ischemic heart disease not amenable to treatment with CABG or PTCA. RESULTS: Fifty-two patients enrolled in this study received IC FGF-2 (0.33 to 48 μg/kg). Hypotension was dose-dependent and dose-limiting, with 36 μg/kg being the maximally tolerated dose. Four patients died and four patients had non-Q-wave myocardial infarctions. Laboratory parameters and retinal examinations showed mild and mainly transient changes during the 6-month follow-up. There was an improvement in quality of life as assessed by Seattle Angina Questionnaire and improvement in exercise tolerance as assessed by treadmill exercise testing (510 ± 24 s at baseline, 561 ± 26 s at day 29 [p = 0.023], 609 ± 26 s at day 57 (p < 0.001), and 633 ± 24 s at day 180 (p < 0.001), overall p < 0.001). Magnetic resonance (MR) imaging showed increased regional wall thickening (baseline: 34 ± 1.7%, day 29: 38.7 ± 1.9% [p = 0.006], day 57: 41.4 ± 1.9% [p < 0.001], and day 180: 42.0 ± 2.3% [p < 0.001], overall p = 0.001) and a reduction in the extent of the ischemic area at all time points compared with baseline. CONCLUSIONS: Intracoronary administration of rFGF-2 appears safe and is well tolerated over a 100-fold dose range (0.33 to 0.36 μk/kg). Preliminary evidence of efficacy is tempered by the open-label uncontrolled design of the study. (C) 2000 by the American College of Cardiology.

Original languageEnglish (US)
Pages (from-to)2132-2139
Number of pages8
JournalJournal of the American College of Cardiology
Volume36
Issue number7
DOIs
StatePublished - 2000

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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