Local perivascular delivery of basic fibroblast growth factor in patients undergoing coronary bypass surgery - Results of a phase I randomized, double-blind, placebo-controlled trial

Background-Angiogenesis is a promising treatment strategy for patients who are not candidates for standard revascularization, because it promotes the growth of new blood vessels in ischemic myocardium. Methods and Results-We conducted a randomized, double-blind, placebo-controlled study of basic fibroblast growth factor (bFGF; 10 or 100 mu g versus placebo) delivered via sustained-release heparin-alginate microcapsules implanted in ischemic and viable but ungraftable myocardial territories in: patients undergoing CABG, Twenty-four patients were randomized to 10 mu g of bFGF (n = 8), 100 mu g of bFGF (n = 8), or placebo (n = 8), in addition to undergoing CABG, There were 2 operative deaths and 3 Q-wave myocardial infarctions. There were no treatment-related adverse events, and there was no rise in serum bFGF levels. Clinical follow-up was available for all patients (16.0 +/- 6.8 months). Three control patients had recurrent angina, 2 of whom required repeat revascularization. One patient in the 10-mu g bFGF group had angina,:whereas all patients in the 100-mu g bFGF group remained angina-free. Stress nuclear perfusion imaging at baseline and 3 months after CABG showed a trend toward worsening of the defect size in the placebo group (20.7 +/- 3.7% to:23.8 +/- 5.7%, P = 0.06), no significant change in the 10-mu g bFGF group, and significant improvement in the 100-mu g bFGF group (19.2 +/- 5.0% to 9.1 +/- 5.9%, P = 0.01). Magnetic resonance assessment of the target ischemic zone in a subset of patients showed a trend toward a reduction in the target ischemic:area in the 100-mu g bFGF group (10.7 +/- 3.9% to 3.7 +/- 6.3%, P = 0.06). Conclusions-This study of bFGF in patients undergoing CABG demonstrates the safety and feasibility of this mode of therapy in patients with viable myocardium that-cannot be adequately revascularized.