Long-term follow-up assessment of a phase 1 trial of angiogenic gene therapy using direct intramyocardial administration of an adenoviral vector expressing the VEGF121 cDNA for the treatment of diffuse coronary artery disease. Academic Article uri icon

Overview

MeSH

  • Aged
  • Coronary Artery Bypass
  • DNA, Complementary
  • Female
  • Follow-Up Studies
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Myocardial Ischemia
  • Thoracotomy
  • Time Factors

MeSH Major

  • Adenoviridae
  • Coronary Artery Disease
  • Genetic Therapy
  • Genetic Vectors
  • Vascular Endothelial Growth Factor A

abstract

  • On the basis of studies in experimental animals demonstrating that AdVEGF121, an E1(-)E3(-) serotype 5 adenovirus coding the 121 isoform of vascular endothelial growth factor (VEGF), could mediate the generation of new blood vessels and reverse coronary ischemia, a clinical study of direct myocardial administration of AdVEGF121 was initiated in patients with late-stage, diffuse coronary artery disease. This study provides long-term (median, 11.8 years) follow-up on these patients. From 1997 to 1999, AdVEGF121 was administered by direct myocardial injection to an area of reversible ischemia in 31 patients with severe coronary disease, either as an adjunct to conventional coronary artery bypass grafting (group A) or as minimally invasive sole (MIS) therapy, using a minithoracotomy (group B). There was no control group; the study participants served as the control subjects. The 5- and 10-year survival was 10 of 15 (67%) and 6 of 15 (40%) for the group A patients, and 11 of 16 (69%) and 5 of 16 (31%) for group B sole therapy patients, respectively. In comparison, maximal medical therapy in comparable groups in the literature have a 3- to 5-year survival rate of 52 to 59%. For the survivors, the angina score for group A was 3.4±0.5 at time 0 and 1.9±1.0 at last follow-up, and for group B it was 3.4±0.6 and 2.0±1.1, respectively. The incidences of malignancy and retinopathy were no greater than that expected for the age-matched general population. We conclude that adenovirus-mediated VEGF direct myocardial administration to patients with severe coronary artery disease is safe, and future larger trials are warranted to assess efficacy.

publication date

  • February 2013

has subject area

  • Adenoviridae
  • Aged
  • Coronary Artery Bypass
  • Coronary Artery Disease
  • DNA, Complementary
  • Female
  • Follow-Up Studies
  • Genetic Therapy
  • Genetic Vectors
  • Humans
  • Kaplan-Meier Estimate
  • Male
  • Middle Aged
  • Myocardial Ischemia
  • Thoracotomy
  • Time Factors
  • Vascular Endothelial Growth Factor A

Research

keywords

  • Clinical Trial, Phase I
  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3581022

Digital Object Identifier (DOI)

  • 10.1089/hum.2012.137

PubMed ID

  • 23137122

Additional Document Info

start page

  • 203

end page

  • 208

volume

  • 24

number

  • 2