Treating people with reduced blood supply to the legs with substances stimulating new vessel formation (growth factors)


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Background and review question

Different diseases, such as atherosclerosis, can cause reduced blood supply to the legs. Depending on the disease severity this may be associated with symptoms such as leg pain when walking or resting, ulceration (open sores) and gangrene of the leg. Reduced blood supply to the legs affects 3% to 10% of all people and 15% to 20% of people over 70 years of age. It is a major cause of decreased mobility and quality of life and of increased risks for amputation or death.

The treatment strategy generally comprises behavioural changes (e.g. smoking cessation, exercise and diet), drugs (e.g. antiplatelets, statins) and catheter-based or surgical interventions. However, for some patients the only option is leg amputation.

Some substances naturally produced in the body, called growth factors, can stimulate new vessel formation. Nowadays, these substances are laboratory produced with the attempt to treat people with reduced blood supply to the legs. Therefore, we evaluated the evidence from clinical studies on the effects of growth factors in those people.

Key results and implications

We identified 20 studies and analysed the results of 14 published studies involving approximately 1400 patients and assessing three types of growth factors (evidence current to June 2016).

Our review shows that the effects of growth factors on the most important clinical parameters comprising limb amputations above the ankle, death and adverse events are uncertain (low-quality evidence up to two years, although moderate-quality evidence for one year). However, the rate of all limb amputations may decrease (low-quality evidence). In addition, growth factors may improve parameters of blood flow (low-quality evidence), ulceration (very low-quality evidence) and rest pain (very low-quality evidence) at up to one year, but have little or no effect on walking ability (low-quality evidence). We downgraded the quality of evidence mostly due to low statistical power and poor study quality. We did not identify any relevant differences in effects between growth factors.

This review does not support growth factor therapy in people with reduced blood supply to the legs to prevent limb amputations above the ankle or death or to improve walking ability. However, using growth factors may improve parameters of blood flow and prevent limb amputations below the ankle with an uncertain effect on adverse events; an improvement of ulceration and rest pain is very uncertain. New high-quality studies are needed to generate evidence with more certainty.