Author + information
- Cindy L Grines, MD, FACC*,* (, )
- Matthew W Watkins, MD, FACC†,
- John J Mahmarian, MD, FACC‡,
- Ami E Iskandrian, MD, FACC§,
- Jeffrey J Rade, MD, FACC∥,
- Pran Marrott, MRCP, MSc¶,
- Craig Pratt, MD, FACC†,
- Neal Kleiman, MD, FACC†,
- for the Angiogenic GENe Therapy (AGENT-2) Study Group
- ↵*Reprint requests and correspondence:
Dr. Cindy L. Grines, Division of Cardiology/3rd Floor Heart Center, William Beaumont Hospital, 3601 West 13 Mile Road, Royal Oak, Michigan 48073-6769, USA.
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 1010adenoviral 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.
☆ Supported by a grant from Berlex Inc, and Collateral Therapeutics Inc. All authors, except Pran Marrott, received research funding for AGENT-2.
- American College of Cardiology Foundation