Critical Limb Ischemia (CLI) is a chronic condition and the most serious form of peripheral arterial disease (PAD). It is a major global health problem with a high and growing incidence, severe impact on patient quality of life and limited treatment options.
CLI is a common condition, in the United States and Europe affecting 1-1.5% of the population aged over 40(1,2,3). Diabetes significantly increases the risk of both PAD and CLI with diabetic patients over 50 years old having a prevalence of CLI of 5.8%(4). Incidence of the disease is growing due to impact of the ageing population and the growing incidence of diabetes.
CLI results from a severe blockage of arteries in the lower limbs. The condition results in significant pain in the feet or toes even at rest. Complications include ulcers in the legs and feet that do not heal and commonly lead to gangrene and amputation of the affected limb. Amputation rates are high with an overall rate within one year of diagnosis estimated at 25%(5), but vary according to the severity of the condition with rates of 11% in patients with superficial ulcers up to 83% in patients with gangrene(6). In addition to limb loss, CLI is associated with a high risk of cardiovascular events, including myocardial infarction, stroke and death. The mortality risk has been reported to be as high as 20-25% within one year of diagnosis and surpasses 50% at 5 years post-diagnosis(7,8,9).
Management of CLI and foot ulcers is largely determined by degree of vascularity in the limb of the affected patient. For patients where the overall vasculature of the limb is not compromised (represents the minority of patients), rest, elevation of the affected foot, and relief of pressure are relatively effective treatments.
The majority of CLI patients (up to 60%) are eligible for manual revascularisation either by radiographic angiography or peripheral artery bypass graft. Up to two thirds of these patients respond to treatment. However the remaining 40% of patients are ineligible for revascularisation and a further 20% of patients do not respond to treatment. For these patients, treatment options are limited to symptomatic treatment of pain and ulcers. For a significant proportion of these patients, major or minor amputation will be required to address complications of deep ulcers and gangrene or to address chronic pain, which does not respond to analgesics. The likelihood of amputation increases according to the severity of the disease.
Given the limitations of current treatments and the severity of the condition there is an urgent need for effective new treatments.
40% of CLI patients are ineligible
25% of CLI patients are likely to be
amputated within one year of diagnosis