**2. Use of statins in world wild practice**

The effectiveness of statins in familial hypercholesterolemia can be judged primarily by the degree of decrease in serum LDL cholesterol levels. The European and International Atherosclerosis Societies stated that, based on the available data, the hypothesis of atherogenesis associated with high LDL-C levels is no longer a hypothesis and can be considered a proven fact [6]. Randomized studies show that the effect of LDL-C on the development of atherosclerotic vascular disease is determined not only by the absolute level of LDL cholesterol, but also by its cumulative effect on the arterial wall [6–8]. It is known that the cumulative effect of LDL-C increases with age and is 160 mmol in a healthy person by the age of 55. In the absence of treatment, patients with familial hypercholesterolemia reach this value from the age of 35. It has been shown that starting statin therapy from 18 years of age allows this cumulative load to be postponed to 48 years of age. When statins are taken from the age of 10, the accumulation of LDL-C of 160 mmol is achieved only by the age of 53, which is close to the indicators of healthy people [9].

Demonstrated clinically significant reduction in LDL cholesterol levels in children with familial hypercholesterolemia taking statins compared with children receiving placebo. Moreover, the degree of reduction varied depending on the dose and the drug used. In the work of S.B. Clauss et al. (2005) [10] described the experience of using lovastatin in girls with familial hypercholesterolemia at a dose of 20–40 mg/day for 24 weeks. The authors concluded that in the lovastatin group there was a significant decrease in LDL cholesterol from baseline by 23–27%, total cholesterol by 17–22%, and apolipoprotein B by 20–23%. In another study, pravastatin versus placebo in children with familial hypercholesterolemia younger than 14 years old at a dose of 20 mg/day and over 14 years old - at a dose of 40 mg/day with a duration of therapy of 104 weeks, the decrease in LDL cholesterol levels reached 24.1% [11]. A number of works have been devoted to the experience of using atorvastatin in childhood. It was shown that the appointment of atorvastatin at a dose of 20–40 mg/day compared with placebo for 6–48 months led to a significant decrease in LDL cholesterol by an average of 32–39%, total cholesterol by 32%, triglycerides by 12% and apolipoprotein B by 34% [12–14]. It should be noted that in one of the studies, a statistically significant increase in the level of HDL cholesterol by 2.8% was stated [12]. In a study by H.J. Avis et al. (2010) [15], who studied the efficacy of rosuvastatin in children with familial hypercholesterolemia compared with placebo, showed a decrease in LDL cholesterol, total cholesterol and apolipoprotein B levels for all three doses (5 mg, 10 mg and 20 mg) with a duration of 12 week Thus, in general, the results of studies evaluating the effects of statins in familial hypercholesterolemia demonstrate the effectiveness of statins in lowering LDL cholesterol and total cholesterol levels in children.

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*Statins for Children with Familial Hypercholesterolemia DOI: http://dx.doi.org/10.5772/intechopen.96007*

compared with that in healthy peers who received placebo.

therapy at the age of 8–10 years [9, 20–23].

**4. Long-term studies of the effectiveness of statins in childhood**

**5. Features of statins usage in children with FH in clinical practice**

[24] and energy metabolism [25], as well as the child's growth [26].

In clinical practice, along with an increase in the frequency of statin use, their side effects are increasingly the subject of research. In adults, statin-related side effects include elevated liver transaminases, creatine kinase, and rhabdomyolysis [24]. The main concerns in the pediatric population are the risk of developing myalgias, as well as the possible effect of statins on liver function [13, 19], cholesterol-dependent production of steroid hormones in the gonads and adrenal glands

In a number of studies, when using statins in children with familial hypercholesterolemia, it is noted the occurrence of muscle pain: when taking pitavastatin, they

The need for long-term studies to assess the effectiveness of statins in childhood has been repeatedly emphasized. In October 2019, a group of scientists published the results of the longest to date follow-up of children with familial hypercholesterolemia taking statins [8]. 214 patients with this disease and their 95 healthy brothers and sisters were under observation for 20 years. It was found that patients taking statins did not significantly differ from their healthy siblings in terms of an increase in the thickness of the intima-media complex. At the same time, the incidence of cardiovascular diseases and mortality from them at the age of 39 years among patients with familial hypercholesterolemia was lower than among their parents suffering from this disease, and amounted to 1% versus 26% and 0 versus 7%, respectively. These studies make it possible to substantiate the need for the use of statins for the primary prevention of complications and increase life expectancy in children with familial hypercholesterolemia. The effectiveness of treatment depends on the dose of drugs and the age of initiation of therapy. The authors of these and a number of other clinical studies emphasize the need to start statin

**3. Effect of statins on the thickness of the intima-media complex**

Another important endpoint for determining the effectiveness of statins is the thickness of the intima-media complex, a clinically significant marker of cardiovascular disease. It is noted that the thickness of the intima-media complex in children depends on age, gender and LDL cholesterol level [16]. In children with familial hypercholesterolemia, a much faster increase in this parameter with age was found than in healthy brothers and sisters [17]. Currently, there is a number of studies demonstrating the effect of statins on reducing the thickness of the intima-media complex. M.J. Braamskamp et al. [18] found that in the case of initiation of statin therapy in familial hypercholesterolemia from the age of 12 years, the thickening of the intima-media complex in children occurs more slowly than in peers with familial hypercholesterolemia who do not take statins. The authors concluded that early initiation of statin treatment can delay atherosclerotic changes in the vessels in adolescents and young adults [18]. Statin therapy also has a positive effect on markers of atherosclerosis such as flow-dependent vasodilation. In a study by S. De Jongh et al. (2002) [19], it was found that against the background of 28-week treatment with simvastatin, the flow-dependent vasodilation significantly improved by an average of 4% in children with heterozygous familial hypercholesterolemia

*Management of Dyslipidemia*

complications.

**2. Use of statins in world wild practice**

intracellular cholesterol and the level of circulating LDL-C in the blood. In addition to the lipid-lowering effect, statins affect atherosclerotic plaque (reduce its size, stabilize the surface, thereby reducing the risk of rupture and ulceration), as well as inflammatory factors and endothelial function (pleiotropic effects) [5]. The main goal of prescribing statins in familial hypercholesterolemia is to reduce the risk and rate of development of atherosclerosis and coronary heart disease in order to delay the onset of cardiovascular accidents as much as possible. It should be noted that the use of statins among the adult population, as a rule, is not in doubt, while the pharmacotherapy of hypercholesterolemia in pediatrics raises questions from doctors and parents regarding its effectiveness, long-term prospects and possible

The effectiveness of statins in familial hypercholesterolemia can be judged primarily by the degree of decrease in serum LDL cholesterol levels. The European and International Atherosclerosis Societies stated that, based on the available data, the hypothesis of atherogenesis associated with high LDL-C levels is no longer a hypothesis and can be considered a proven fact [6]. Randomized studies show that the effect of LDL-C on the development of atherosclerotic vascular disease is determined not only by the absolute level of LDL cholesterol, but also by its cumulative effect on the arterial wall [6–8]. It is known that the cumulative effect of LDL-C increases with age and is 160 mmol in a healthy person by the age of 55. In the absence of treatment, patients with familial hypercholesterolemia reach this value from the age of 35. It has been shown that starting statin therapy from 18 years of age allows this cumulative load to be postponed to 48 years of age. When statins are taken from the age of 10, the accumulation of LDL-C of 160 mmol is achieved only

by the age of 53, which is close to the indicators of healthy people [9].

Demonstrated clinically significant reduction in LDL cholesterol levels in children with familial hypercholesterolemia taking statins compared with children receiving placebo. Moreover, the degree of reduction varied depending on the dose and the drug used. In the work of S.B. Clauss et al. (2005) [10] described the experience of using lovastatin in girls with familial hypercholesterolemia at a dose of 20–40 mg/day for 24 weeks. The authors concluded that in the lovastatin group there was a significant decrease in LDL cholesterol from baseline by 23–27%, total cholesterol by 17–22%, and apolipoprotein B by 20–23%. In another study, pravastatin versus placebo in children with familial hypercholesterolemia younger than 14 years old at a dose of 20 mg/day and over 14 years old - at a dose of 40 mg/day with a duration of therapy of 104 weeks, the decrease in LDL cholesterol levels reached 24.1% [11]. A number of works have been devoted to the experience of using atorvastatin in childhood. It was shown that the appointment of atorvastatin at a dose of 20–40 mg/day compared with placebo for 6–48 months led to a significant decrease in LDL cholesterol by an average of 32–39%, total cholesterol by 32%, triglycerides by 12% and apolipoprotein B by 34% [12–14]. It should be noted that in one of the studies, a statistically significant increase in the level of HDL cholesterol by 2.8% was stated [12]. In a study by H.J. Avis et al. (2010) [15], who studied the efficacy of rosuvastatin in children with familial hypercholesterolemia compared with placebo, showed a decrease in LDL cholesterol, total cholesterol and apolipoprotein B levels for all three doses (5 mg, 10 mg and 20 mg) with a duration of 12 week Thus, in general, the results of studies evaluating the effects of statins in familial hypercholesterolemia demonstrate the effectiveness of statins in lowering LDL cholesterol

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and total cholesterol levels in children.
