PATIENT
PHYSICIANS
Chronic lower limb ischemia — is a frequent pathological condition in which atherosclerosis affects the vessels of the legs. As a result, the lower limb muscles do not receive the necessary amount of blood with a dissolved oxygen and nutrients. The patient feels this as pain, that occurs after the physical load on the legs, such as walking.
In medicine, this phenomenon is called «intermittent claudication», due to the fact that in connection with the occurrence of severe pain a person is forced to stop for a while to rest and only then continue on their way. Depending on the severity of the disease, such stops are rare or frequent. For example, when the disease stage 2b ( classification Pokrovsky-Fontaine), the patient can go without pain just 200 meters away, and at 3 — no more than 25 meters. (Fig. 1).
Chronic lower limb ischemia (IIIb stage), manifested by the following symptoms: pain when walking that force to stop.
«intermittent claudication»;
color of the skin of the affected limb paler (marbled colors) than the healthy leg;
a decrease of the tibia (compared with healthy);
foot chilliness;
dry leg skin;
breakage and (or) slow nail growth.
When Critical Limb Ischemia (III-IV stage) is diagnosed the following symptoms are usually found:
pain at rest;
ulcerous-necrotic changes in tissues of the legs.
Approximately 5% of the population older than 50 years at inspection can detect signs of ischemia of the lower limbs, but only about 50% of patients get diagnosed in time. Since about 30% of the lower limb ischemia cases without treatment can be fatal it is very important to diagnose and treat this disease early, after 10 years, the risks increases up to 50%. The main causes of death of patients: myocardial infarction (60%) the stroke (12%) of cases.
The main feature of the disease is that the lower limb ischemia rarely manifests itself at an early stage. The first symptoms appear only after vascular occlusion has decreased the blood flow by no less than 50%. But more often the patient does not pay attention until the narrowing of the blood vessels by 70-80% causing irreversible changes.
A series of studies are conducted for the diagnosis of the disease «atherosclerosis of the lower extremity arteries», including analysis of the patient’s complaints, inspection and instrumental methods of diagnosis. The most common and simple method of investigation to establish the diagnosis is the measurement of ankle-brachial index (ABI). In this case the doctor measures the blood pressure in the ankle area and at the shoulder level. Another very common instrumental method — duplex ultrasound scanning, which allows to visually assess the size and shape of the atherosclerotic plaque, to evaluate the velocity of blood flow within the vessel.
This information helps to understand the nature and degree of the vessel occlusion -stenosis. If necessary, angiography using CT (computed tomography) or MRI (magnetic resonance imaging) is performed. Angiography using these methods allows to accurately determine the extent and localization of vascular atherosclerotic plaque. According to the results of the research doctor can determine the most appropriate for a particular patient’s treatment approach.
Treatment of patients with lower limb ischemia may be surgical or conservative with therapeutics of different modality.
All treatments of lower limb ischemia can be divided into four groups, depending on the mechanism of action of particular drug:
Drugs affecting vascular tone and blood rheology, Anticoagulants, Antiplatelet agents and Peripheral Vasodilators. Such drugs optimize vascular tone, improve the rheological properties of blood. In a separate subgroup are such drugs as prostaglandins and prostacyclins, they are important as they also improve the peripheral vascular tone and blood rheology. The indications for their use are severe chronic arterial and venous insufficiency.
Drugs with a mechanism of action «therapeutic angiogenesis»represent a new approach in the treatment of lower limb ischemia. The indication for their use is lower limb ischemia IIa-III stage (Pokrovsky-Fontaine).
Angiogenesis — the process of growth and development of new vessels. Therapeutic angiogenesis — a therapeutic strategy based on stimulation by the drug of the natural process of angiogenesis. In other words, the application of therapeutic angiogenesis uses the evolutionary programmed mechanism of blood vessel formation and growth for treating lower limb ischemia. The emergence and growth of new blood vessels in patients with lower limb ischemia occurs in the region of greatest vascular occlusions. The growth of new blood vessels after the treatment is based on the principle of shunts. It lasts about three months, after which the structure of the new vessel is stabilized and the patient feels improvements (for example, may increase the distance walking without pain, there is no leg coldness, improved condition of the skin), blood flow increases and improves the process of oxygen utilization in the tissues of the limb. Therapeutic angiogenesis contributes to all those improvements that last for at least three years.
In patients with clinical manifestations of atherosclerosis and hyperlipidemia, drugs lowering cholesterol, particularly Low density Lipids (LDL) and Very Low Density Lipids (VLDL) not only have a preventive effect, but also a curative effect. Cholesterol synthesis inhibitors may be used to overcome high cholesterol eating habits, such as statins, calcium antagonists ions, multicomponent drugs and garlic containing drugs. Such treatment must be long-term (up to 8 months or more). Vitamins and stimulators of metabolism. This group of drugs is extremely important for the treatment of vascular diseases. These drugs are shown to be useful for all stages of cardiovascular diseases. The need for their application was determined long ago. In recent years, new effective drugs of this group are being developed which greatly increased the importance of this group of drugs.
Neovasculgen® innovative drug designed to provide additional blood flow to ischemic tissues of affected limb on the principle of so-called «therapeutic angiogenesis.» Active ingredient of the drug is a DNA sequence encoding a specialized protein synthesis, providing the growth of blood vessels — so-called Vascular Endothelial Growth Factor (VEGF). After intramuscular administration of Neovasculgen® tissues start in 2-4 weeks to produce the factor that leads to the development of the new vessels. With time (several months) such vessels may increase in diameter, which will provide an even greater flow of blood. Subjectively, ie by the patient, the effect of the drug is felt in the form of a disappearance of pain when walking, or a delay in the pain onset. It was found that six months after the treatment with Neovasculgena® there was an increase in pain-free walking distance of about 300 meters on average, in different groups of patients with different degrees of the disease — on average, up to 500-600 meters, and in some — up to 3000 meters or more. Importantly, the resulting effect is not only persists for at least 3 years after the course of treatment (according to the data published by the end of 2015), but also increases and reaches its maximum for the second year after the course of treatment.
In this way, the primary clinical benefit from the inclusion of the drug in the treatment program of patients (in combination with antiplatelet therapy) is a significant increase in pain-free walking distance — enabling patients to move and walk a relatively large distance and self-service, i.e. improving the quality of life of these patients. However, it should be stressed that the drug is not a substitute for surgical treatment and, as shown it has a supporting role for surgical revascularisation. However, in cases where the operation is impossible, Neovasculgen® remains one of the few chances for a patient to keep the limb function.
