A randomized, double-blind, placebo-controlled trial of Ad5FGF-4 gene therapy and its effect on myocardial perfusion in patients with stable angina

J Am Coll Cardiol. 2003 Oct 15;42(8):1339-47. doi: 10.1016/s0735-1097(03)00988-4.


Objectives: The primary objective of this study was to determine whether intracoronary administration of the adenoviral gene for fibroblast growth factor (Ad5FGF-4) can improve myocardial perfusion compared with placebo.

Background: Animal studies and observational clinical studies have shown improvement in perfusion of the ischemic myocardium using genes encoding angiogenic growth factors; however, randomized, double-blind data in humans are lacking.

Methods: We performed a randomized, double-blind, placebo-controlled trial of intracoronary injection of 10(10) adenoviral particles containing a gene encoding fibroblast growth factor (Ad5FGF-4) to determine the effect on myocardial perfusion. Fifty-two patients with stable angina and reversible ischemia comprising >9% of the left ventricle on adenosine single-photon emission computed tomography (SPECT) imaging were randomized to gene therapy (n = 35) or placebo (n = 17). Clinical follow-up was performed, and 51 (98%) patients underwent a second adenosine SPECT scan after 8 weeks.

Results: Overall (n = 52), the mean total perfusion defect size at baseline was 32.4% of the left ventricle, with 20% reversible ischemia and 12.5% scar. At eight weeks, Ad5FGF-4 injection resulted in a significant reduction of ischemic defect size (4.2% absolute, 21% relative; p < 0.001) and placebo-treated patients had no improvement (p = 0.32). Although the change in reversible perfusion defect size between Ad5FGF-4 and placebo was not significant (4.2% vs. 1.6%, p = 0.14), when a single outlier was excluded a significant difference was observed (4.2% vs. 0.8%, p < 0.05). Ad5FGF-4 was well tolerated and did not result in any permanent adverse sequelae.

Conclusions: Intracoronary injection of Ad5FGF-4 showed an encouraging trend for improved myocardial perfusion; however, further studies of therapeutic angiogenesis with Ad5FGF-4 will be necessary.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine
  • Adenoviridae / genetics*
  • Angina Pectoris / diagnostic imaging
  • Angina Pectoris / physiopathology
  • Angina Pectoris / therapy*
  • Coronary Circulation / physiology*
  • Double-Blind Method
  • Female
  • Fibroblast Growth Factor 4
  • Fibroblast Growth Factors / administration & dosage
  • Fibroblast Growth Factors / genetics
  • Fibroblast Growth Factors / therapeutic use*
  • Follow-Up Studies
  • Genetic Therapy / methods*
  • Genetic Vectors / administration & dosage
  • Humans
  • Injections, Intra-Arterial
  • Male
  • Middle Aged
  • Proto-Oncogene Proteins / administration & dosage
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / therapeutic use*
  • Radiopharmaceuticals
  • Technetium Tc 99m Sestamibi
  • Time Factors
  • Tomography, Emission-Computed, Single-Photon


  • FGF4 protein, human
  • Fibroblast Growth Factor 4
  • Proto-Oncogene Proteins
  • Radiopharmaceuticals
  • Fibroblast Growth Factors
  • Technetium Tc 99m Sestamibi
  • Adenosine