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. Importantly CLI has currently, limited treatment options and has a severe impact on the patient’s quality of life.
CLI results from a severe blockage of the arteries in the lower limbs Symptoms include severe burning 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 for which amputation of the affected limb is the only treatment option. The global amputation rate is estimated at 25% (5) within one year of diagnosis, but vary according to the severity of the condition with rates of 11% in patients with superficial ulcers and 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).
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 the ageing population and the growing incidence of diabetes.
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