Grant: Project Grant

Peripheral artery disease (PAD) is caused by fatty deposit build-up (atherosclerotic plaques) within an inflamed arterial wall that obstructs blood flow in leg arteries. The reduced blood flow to the legs can cause disabling leg pain and limit walking. Other arteries, such as those supplying the heart and brain, are commonly affected too. Inflamed arteries are more prone to the sudden formation of blood clots. These clots can completely obstruct blood flow and lead to acute complications such as leg gangrene, heart attack and stroke. Surgery to open up arteries, blood thinning medications, blood pressure control and cholesterol lowering therapies can help prevent and treat these complications but about one-third of patients still end up with these complications. None of the existing therapies target inflammation. Because a major driver of plaque build-up and clotting is inflammation in the blood vessel wall, we believe that it makes sense to develop anti-inflammatory medicines to heal the arteries to reduce the risk of long term complications. The main aim of the LEADER-PAD research program is to examine whether an anti-inflammatory drug, colchicine, will reduce complications in patients with PAD. This medication lowers complication rates by about 25% in patients with angina or heart attack, but has not been studied in patients with PAD, who would likely derive an even greater benefit because of the widespread atherosclerosis. As a first step, we will evaluate the feasibility of conducting such a definitive multicenter randomized trial in this (vanguard) proposal.