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Angiogenic Therapy Appears To Reduce Claudication

Angiogenic therapy which combines genes, proteins, and other molecular agents to stimulate growth of new blood vessels has demonstrated improvement in peripheral blood flow for patients with intermittent claudication caused by atherosclerosis.

In a trial involving 174 patients at 22 centres across the United States, investigators using recombinant fibroblast growth factor-2 (rFGF-2) have provided evidence of clinical therapeutic angiogenesis by intra-arterial infusion of an angiogenic protein.

The Therapeutic Angiogenesis With FGF for Intermittent Claudication (TRAFFIC) trial -- a phase II randomized double-blind controlled study -- was directed by Dr Robert Lederman, then at the University of Michigan and now at the National Heart Lung and Blood Institute, National Institutes of Health, Bethesda, Maryland, and Dr Brian Annex, Duke University Medical Center, Durham, North Carolina.

Investigators point out that the protein recombinant fibroblast growth factor-2 (rFGF-2) can cause growth and proliferation of blood vessels from existing vascular structures. They aimed to test the hypothesis that rFGF-2 improves treadmill performance in patients with intermittent claudication of the leg caused by infra-inguinal obstructive atherosclerosis.

The rFGF-2 used in the trial was a 146 amino acid, non-glycosylated, monomeric, 16·5 kDa protein, which is produced in genetically engineered yeast.

Investigators enrolled 190 patients with intermittent claudication of the calf muscle caused by atherosclerosis. They were randomly assigned bilateral intra-arterial infusions of placebo on days one and 30 (the control group); rFGF-2 (30 g/kg) on day one and placebo on day 30 (single-dose group); or rFGF-2 (30 g/kg) on days one and 30 (double-dose group). Data were available for 174 of the 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. Two doses over 30 days were not superior to one dose, but alternate dosing regimens could warrant further consideration, the investigators add.

The TRAFFIC trial did not look at the effects of other treatments for intermittent claudication, particularly concurrent structured exercise or cilostazol. In addition, there was no significant difference in claudication onset time or quality of life between treatment groups.

In a separate comment on the trial, Dr Annex said: "This is the third large multi-center randomized placebo-controlled trial looking at the therapeutic use of an angiogenic agent and the first to show a positive result in its primary endpoint. This study provides the strongest and most convincing data to date that an angiogenic agent can have a positive effect in humans."
Lancet 2002; 359: 2053-58. "Therapeutic angiogenesis with recombinant fibroblast growth factor-2 for intermittent claudication (the TRAFFIC study): a randomised trial"

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