Effects at a single intracoronary injection of basic fibroblast growth factor in stable angina pectoris

We sought to evaluate safety, tolerability, pharmacokinetics, and pharmacod ynamics of basic fibroblast growth factor (bFGF), administered as a single intracoronary injection, to subjects with stable angina pectoris secondary to coronary artery disease. bFGF, on angiogenic growth factor, has been sho wn to enhance collateral development in animal models of progressive corona ry occlusion. To our knowledge, this study represents the initial introduct ion of parenteral bFGF into humans. This was a phase 1, randomized, dose-es calation trial of bFGF in 25 subjects with coronary artery disease and stab le angina. Subjects were randomized 2:1 to a single dose of bFGF or placebo , injected into the left main coronary artery. bFGF doses ranged from 3 to 100 mu g/kg, increasing in half-log increments. bFGF was generally well tol erated at doses of 3 to 30 mu g/kg. Plasma clearance was 20 +/- 2 ml/kg/min , with an elimination half-life of 85 +/- 11 minutes. bFGF caused acute hyp otension (approximate to 10%) that did not appear to be dose-related throug h the dose range studied. Of the 9 subjects who received 30 to 100 mu g/kg bFGF, 2 had sustained hypotension, mild to moderate in severity, lasting 1 to 3 days, and 3 subjects developed bradycardia hours to days after bFGF ad ministration. bFGF dilated epicardial coronary arteries (7.4 +/- 2.5% mean diameter increase, p < 0.02). Transient mild thrombocytopenia and proteinur ia were observed in some subjects in the 30-mu g/kg cohort. No subject had signs suggesting systemic angiogenesis. Thus, intracoronary bFGF, at doses of 3 to 30 mu g/kg, was generally well tolerated in subjects with stable an gina. (C) 2000 by Excerpta Medico, Inc.