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

Abstract

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 μg 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 μg of bFGF (n=8), 100 μg 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-μg bFGF group had angina, whereas all patients in the 100-μg 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-μg bFGF group, and significant improvement in the 100-μg 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-μg 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.