title: Angiogenic Gene Therapy (AGENT) trial in patients with stable angina pectoris.
abstract: BACKGROUND
  The angiogenic response to myocardial ischemia can be augmented in animal models by gene transfer with the use of a replication defective adenovirus (Ad) containing a human fibroblast growth factor (FGF) gene.
  
  
  RESULTS
  The objectives of the Angiogenic GENe Therapy (AGENT) trial were to evaluate the safety and anti-ischemic effects of 5 ascending doses of Ad5-FGF4 in patients with angina and to select potentially safe and effective doses for subsequent study. Seventy-nine patients with chronic stable angina Canadian Cardiovascular Society class 2 or 3 underwent double-blind randomization (1:3) to placebo (n=19) or Ad5-FGF4 (n=60). Safety evaluations were performed at each visit and exercise treadmill testing (ETT) at baseline and at 4 and 12 weeks. Single intracoronary administration of Ad5-FGF4 seemed to be safe and well tolerated with no immediate adverse events. Fever of <1-day duration occurred in 3 patients in the highest-dose group. Transient, asymptomatic elevations in liver enzymes occurred in 2 patients in lower-dose groups. Serious adverse events during follow-up (mean, 311 days) were not different between placebo and Ad5-FGF4. Overall, patients who received Ad5-FGF4 tended to have greater improvements in exercise time at 4 weeks (1.3 versus 0.7 minutes, P=NS, n=79). A protocol-specified, subgroup analysis showed the greatest improvement in patients with baseline ETT < or =10 minutes (1.6 versus 0.6 minutes, P=0.01, n=50).
  
  
  CONCLUSIONS
  Results show evidence of favorable anti-ischemic effects with Ad5-FGF4 compared with placebo, and it appears to be safe. Angiogenic gene transfer with Ad5-FGF4 shows promise as a new therapeutic approach to the treatment of angina pectoris.
authors.affiliation: Division of Cardiology, William Beaumont Hospital, 3601 W 13 Mile Road, Royal Oak, MI 48073-6769, USA. cgrines@beaumont.edu
authors.forename: Cindy L
authors.initials: CL
authors.lastname: Grines
authors.forename: Matthew W
authors.initials: MW
authors.lastname: Watkins
authors.forename: Greg
authors.initials: G
authors.lastname: Helmer
authors.forename: William
authors.initials: W
authors.lastname: Penny
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Brinker
authors.forename: Jonathan D
authors.initials: JD
authors.lastname: Marmur
authors.forename: Andrew
authors.initials: A
authors.lastname: West
authors.forename: Jeffery J
authors.initials: JJ
authors.lastname: Rade
authors.forename: Pran
authors.initials: P
authors.lastname: Marrott
authors.forename: H Kirk
authors.initials: HK
authors.lastname: Hammond
authors.forename: Robert L
authors.initials: RL
authors.lastname: Engler
mesh_terms: D000256:Adenoviridae / Q000235:genetics*; D000328:Adult; D000368:Aged; D000787:Angina Pectoris / Q000628:therapy*; D015331:Cohort Studies; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004452:Echocardiography; D005080:Exercise Test / Q000187:drug effects; D005260:Female; D005346:Fibroblast Growth Factors / Q000008:administration & dosage* / Q000009:adverse effects / Q000235:genetics; D005500:Follow-Up Studies; D015316:Genetic Therapy / Q000009:adverse effects / Q000379:methods*; D005822:Genetic Vectors / Q000008:administration & dosage / Q000009:adverse effects / Q000235:genetics; D006801:Humans; D007269:Injections, Intra-Arterial; D008099:Liver / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008875:Middle Aged; D018919:Neovascularization, Physiologic; D016896:Treatment Outcome
chemical_list: C112971:fibroblast growth factor 14; D005346:Fibroblast Growth Factors