Peripheral artery disease affects up to 15% of adults over the age of 55 years; a third are estimated to have typical intermittent claudication (cramp-like pain in the legs during exercise caused by restricted blood flow, often a result of obstructive atherosclerosis). The protein recombinant fibroblast growth factor-2 (rFGF-2) can cause growth and proliferation of blood vessels from existing vascular structures (angiogenesis). Robert Lederman, formerly of the University of Michigan, Brian Annex from Duke University Medical Centre, USA, and colleagues investigated whether one or two doses of intra-arterial rFGF-2 improves exercise capacity in patients with moderate-to-severe intermittent claudication (the TRAFFIC study).
190 patients with intermittent claudication of the calf muscle caused by atherosclerosis were randomly assigned bilateral intra-arterial infusions of placebo on days 1 and 30 (the control group); rFGF-2 (30 mg/kg) on day 1 and placebo on day 30 (single-dose group); or rFGF-2 (30 mg/kg) on days 1 and 30 (double-dose group).
Data were available for 174 patients. Peak walking time at 90 days was increased by 0.6 minutes with placebo, by 1.77 minutes with single-dose rFGF-2, and by 1.54 minutes with double-dose rFGF-2.
Robert Lederman comments: "Intra-arterial rFGF-2 resulted in a significant increase in peak walking time at 90 days; repeat infusion at 30 days was no better than one infusion. The findings of TRAFFIC provide evidence of clinical therapeutic angiogenesis by intra-arterial infusion of an angiogenic protein."
In an accompanying Commentary, Richard Donnelly from the University of Nottingham, UK, concludes: "…the TRAFFIC study gives cautious optimism that experimental biotechnology can deliver a safe and effective therapy which, via new vessel formation, improves symptoms and lower-limb outcome in patients with peripheral arterial disease. Therapeutic angiogenesis in the lower limb would be especially attractive when revascularisation is not feasible or has failed, or when the risks of critical ischaemia and distal amputation are high."
Contact: Dr Robert J Lederman MD, National Heart Lung and Blood Institute, National Institutes of Health, 10 Center Drive, Building 10, Room 2c713, Bethesda, MD 20892-1538, USA; T) +1 301 402 6769; F) +1 301 451 5451; E) lederman@nih.gov
Dr Brian H Annex, MD, Duke University Medical Center, 508 Foulton St. Box 111A, Durham, NC 27705, USA; T) +1 919 286-0411 extension 7258; F) +1 919 286-6861; E) annex001@mc.duke.edu.
Professor Richard Donnelly, School of Medical and Surgical Sciences, University of Nottingham, and Southern Derbyshire Acute Hospitals NHS Trust, Derby DE1 2QY, UK; E) Richard.donnelly@nottingham.ac.uk
Journal
The Lancet