Pharmacological Treatment of Coronary Artery Disease With Recombinant Fibroblast Growth Factor-2

Abstract

Background-Single-bolus intracoronary administration of fibroblast growth factor-2 (FGF2) improved symptoms and myocardial function in a phase I, open-label trial in patients with coronary artery disease. We conducted the FGF Initiating RevaScularization Trial (FIRST) to evaluate further the efficacy and safety of recombinant FGF2 (rFGF2). Methods and Results-FIRST is a multicenter, randomized, double-blind, placebo-controlled trial of a single intracoronary infusion of rFGF2 at 0, 0.3, 3, or 30 g/kg (nϭ337 patients). Efficacy was evaluated at 90 and 180 days by exercise tolerance test, myocardial nuclear perfusion imaging, Seattle Angina Questionnaire, and Short-Form 36 questionnaire. Exercise tolerance was increased at 90 days in all groups and was not significantly different between placebo and FGF-treated groups. rFGF2 reduced angina symptoms as measured by the angina frequency score of the Seattle Angina Questionnaire (overall Pϭ0.035) and the physical component summary scale of the Short-Form 36 (pairwise Pϭ0.033, all FGF groups versus placebo). These differences were more pronounced in highly symptomatic patients (baseline angina frequency score Յ40 or Canadian Cardiovascular Society score of III or IV). None of the differences were significant at 180 days because of continued improvement in the placebo group. Adverse events were similar across all groups, except for hypotension, which occurred with higher frequency in the 30-g/kg rFGF2 group.

Acute Systemic Fibroblast Growth Factor-2 Enhances Long-Term Extinction of Fear and Reduces Reinstatement in Rats

“…Given that stress-induced relapse is a significant problem in the treatment of anxiety disorders, the finding that FGF2 reduces reinstatement has potentially important clinical implications. Although FGF2 has been trialed in humans as a potential inducer of angiogenesis (Laham et al, 2000;Lederman et al, 2002;Simons et al, 2002), until now it has not been considered as a potential pharmacological adjunct to exposure therapy.…”

Fibroblast growth factor/fibroblast growth factor receptor system in angiogenesis

“…Also, single-bolus intracoronary FGF2 infusion showed transient beneficial effects, including reduction of angina symptoms, increase of treadmill tolerance and quality of life [237]. Transient beneficial effects were observed also in the phase II trial FIRST in which FGF2 was administered via intracoronary infusion [238]. In PAD patients, a positive response was observed in a phase I trial in which patients with symptoms of claudications and advanced peripheral arterial disease where given intra-arterial FGF2 infusion [239].…”

Controlled delivery of fibroblast growth factor-1 and neuregulin-1 from biodegradable microparticles promotes cardiac repair in a rat myocardial infarction model through activation of endogenous regeneration

“…Thus, there has been great interest in novel therapeutic options, such as gene (reviewed in [2]) and stem cell therapy (reviewed in [3]), or even direct administration of proangiogenic cytokines [4]. In the case of growth factor-based therapy, although preclinical studies and initial clinical trials had suggested beneficial effects [5,6], doubleblinded clinical trials with large cohorts of patients failed to validate the efficacy [7][8][9]. These negative findings may have resulted from issues related to growth factor selection, monotherapy instead of combinatorial therapy, and/or timing of growth factor delivery.…”