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.


RESULTS
We conducted a randomized, double-blind, placebo-controlled study of basic fibroblast growth factor (bFGF; 10 or 100 microg 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 microg of bFGF (n=8), 100 microg 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-microg bFGF group had angina, whereas all patients in the 100-microg 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-microg bFGF group, and significant improvement in the 100-microg 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-microg 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.
Laham
R J
RJ
Angiogenesis Research Center and Interventional Cardiology Section, harvard Medical School and Beth Israel Deaconess Medical Center, Boston, Mass., USA.
Sellke
F W
FW
Edelman
E R
ER
Pearlman
J D
JD
Ware
J A
JA
Brown
D L
DL
Gold
J P
JP
Simons
M
M
D000464:Alginates; D001026:Coronary Artery Bypass; D003331:Coronary Vessels; D003692:Delayed-Action Preparations; D004311:Double-Blind Method; D004337:Drug Carriers; D004339:Drug Compounding; D004343:Drug Implants; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000008:administration & dosage*; D005500:Follow-Up Studies; D020723:Glucuronic Acid; D006493:Heparin; D006603:Hexuronic Acids; D006801:Humans; D008297:Male; D008875:Middle Aged; D018579:Patient Selection; D010919:Placebos; D011994:Recombinant Proteins / Q000008:administration & dosage
D000464:Alginates; D003692:Delayed-Action Preparations; D004337:Drug Carriers; D004343:Drug Implants; D006603:Hexuronic Acids; D010919:Placebos; D011994:Recombinant Proteins; D016222:Fibroblast Growth Factor 2; D020723:Glucuronic Acid; D006493:Heparin