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

Roger J. Laham, Frank W. Sellke, Elazer R. Edelman, Justin D. Pearlman, J. Anthony Ware, David L. Brown, Jeffrey P. Gold, Michael Simons

Research output: Contribution to journalArticle

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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.

Original languageEnglish (US)
Pages (from-to)1865-1871
Number of pages7
JournalCirculation
Volume100
Issue number18
DOIs
StatePublished - Nov 2 1999

Fingerprint

Fibroblast Growth Factor 2
Placebos
Myocardium
Fibroblast Growth Factor 10
Perfusion Imaging
Capsules
Blood Vessels
Heparin
Magnetic Resonance Spectroscopy
Therapeutics
Myocardial Infarction
Safety

Keywords

  • Angiogenesis
  • Growth substances
  • Heart diseases
  • Myocardium

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

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. / Laham, Roger J.; Sellke, Frank W.; Edelman, Elazer R.; Pearlman, Justin D.; Ware, J. Anthony; Brown, David L.; Gold, Jeffrey P.; Simons, Michael.

In: Circulation, Vol. 100, No. 18, 02.11.1999, p. 1865-1871.

Research output: Contribution to journalArticle

Laham, Roger J. ; Sellke, Frank W. ; Edelman, Elazer R. ; Pearlman, Justin D. ; Ware, J. Anthony ; Brown, David L. ; Gold, Jeffrey P. ; Simons, Michael. / 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. In: Circulation. 1999 ; Vol. 100, No. 18. pp. 1865-1871.
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AU - Edelman, Elazer R.

AU - Pearlman, Justin D.

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AU - Gold, Jeffrey P.

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N2 - 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.

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