Резюме
Ліпатнікова А.С., Сабковська Х.О., Холіна О.А., Пілієва О.В. Клініко-патогенетичні особливості лікування статинами
У статті наведені оглядові дані щодо лікування і профілактики ризику ССЗ. Розглянуто наявні переваги застосування розувастатину в порівнянні з іншими статинами. Наведені дані клінічних досліджень і постмаркетингових спостережень. У результатах програми GALAXY показано переваги розувастатину у нормалізації показників ліпідного обміну, маркерів запалення та зворотного розвитку атеросклерозу в коронарних і сонних артеріях
Ключові слова: статини, лікування ССЗ, профілактика, розувастатин.

Резюме
Липатникова А.С., Сабковская К.А., Холина О.А., Пилиева Е.В. Клинико-патогенетические особенности лечения статинами
В статье приведены обзорные данные по лечению и профилактике риска ССЗ. Рассмотрены имеющиеся преимущества применения розувастатина, по сравнению с другими статинами. Приведенны данные клинических исследований и постмаркетинговых наблюдений. В результатах программы GALAXY показаны преимущества розувастатина в нормализации показателей липидного обмена, маркеров воспаления и обратного развития атеросклероза в коронарных и сонных артериях.
Ключевые слова: статины, лечение ССЗ, профилактика, розувастатин.

Summary
Lipatnikova A.S., Sabkovskaya K.A., Holina Е.A., Pilieva E.V. Clinico-pathogenetic features of statin treatment.
This article provides an overview on treatment and prevention of CVD risk. Considered existing advantages of rosuvastatin as compared to other statins. Bringing data from clinical studies and post-marketing observations. In the results of the program GALAXY shows the benefits of rosuvastatin in normalizing lipid metabolism, markers of inflammation and regression of atherosclerosis in the coronary and carotid arteries.
Key words: statins, treatment of CVD, prevention, rosuvastatin.

Рецензент: д.мед.н., проф. Ю.М. Колчін

УДК 616.1+616.71:618.173]-07-08

ДЗ «Луганський державний медичний університет»

ГЗ «Луганский государственный медицинский университет»

State Establishment "Lugansk State Medical University"

boba@dsip.net

Coronary heart disease (CHD ) and other cardiovascular diseases (CVD) are the leading causes of death and serious complications both in Ukraine and in other countries [1,2,3]. Over the past decade, there has been some progress in the treatment of these diseases , which led to a significant improvement in prognosis and quality of life of patients [4]. However, the risk of cardiovascular complications remains high. And , despite the use of modern treatment strategies ( use of drugs with proven positive effect - aspirin , β- blockers, enzyme inhibitors ACE), the progress of the disease can be stopped only a small proportion of patients [ 5].

Therefore, one of the main areas to reduce the risk of cardiovascular complications was the use lipid lipid-lowering therapy. Epidemiological studies have shown a direct correlation between the level of cholesterol ( LDL ) and the risk of coronary heart disease. This has been proven in large studies such as the PSC [ 6 ], MRFIT [ 7] and INTERHEART [ 8]. The benefits of lowering lipid levels has also been demonstrated in prospective meta-analysis of randomized controlled trials to reduce cholesterol that include 90 thousand patients treated with different statins [9]. It was shown that at low lypoproteids- cholesterol , low-density ( LDL ) only 1 mmol / l , a decrease in risk of death: 12% - from all causes by 23% - from all major coronary events by 26% - from acute myocardial infarction by 24 % - from coronary revascularization procedures , 17% - from stroke and 21 % - of total cardiovascular events .

Based on epidemiological data and results of other randomized clinical trials have shown that treatment with higher HDL cholesterol can bring additional benefits regardless of lowering LDL cholesterol [10-12 ]. Different drugs affect the lipid profile. Among the drugs used statins inhibitors certainly a first-line agents in the treatment of dyslipidemia in patients with risk factors for CVD.

In the early stages of the formation acidi mevalonici with HMG-CoA statins competitively inhybitions one of the most important enzymes of cholesterol synthesis - HMG-CoA reductase . As a result, there is a lack of liver cholesterol , which causes the surface expression of hepatocyte additional receptors for LDL. This increases their activity , which ultimately leads to a decrease in the concentration of LDL in plasma [13].

In recent decades, drugs of this class are millions of patients worldwide that are at high risk within secondary prevention.Currently inclinical practice widely used statins several classes, including special place is the drug of last generation - rosuvastatin. Rozuvastatin has undeniable advantages relative to pharmacological and clinical properties, compared with other statins.

This drug has the longest half-life among all statins and is the only statin that is minimallyty metabolic activyty of  cytochrome P450 enzyme system (Sura 450) without significant involvement isoenzyme 3A4. Thus, the probability of rosuvastatin drug interactions and other drugs is very low [19]. Rosuvastatin bioavailability after oral administration is 20%. Constant drug concentration is within 3-5 hours, which is longer than the other statins (usually less than 3 h).

The starting dose is 5-10 mg rosuvastatin and therapeutic effect appears during the first weeks after initiation of therapy. And after two weeks of treatment effect is 90%. The maximum effect of the drug is registered usually the fourth weeks and maintained at a constant reception. Thus, it was shown that rosuvastatin 10 mg / day. reduces LDL cholesterol by 50% ( approximately 2.1 mmol / l with an average cholesterol level ) leads to an increase in HDL-C for 8-14 % [ 14-17 ].

Unlike lovastatin , simvastatin and atorvastatin, subject to minimal hepatic metabolism. Approximately 90% is excreted unchanged through the intestines form, about 5 % is excreted by the kidneys in unchanged form.

 Available benefits rosuvastatin compared to other statins caused  by its ability to interact more with HMG-CoA reduktaz that is associated with a higher affinity for the active site of the enzyme [18].

According to clinical studies and marketing observations, have shown that the drug is well tolerated. Serious adverse events such as myopathy (< 0.1%), rabdomyolyz (< 0.01 %) or hepatitis ( <0.01 %), very rare in treatment at a daily dose of 5-20 mg [ 20,21 ]. When receiving rosuvastatin was registered low percentage occurrence of proteinuria ( 0,2-1,2 %). According to these studies, proteinuria was transitory and was not associated with impaired renal function [20,21 ]. Lipid-lowering therapy has become an essential component in the treatment and prevention of diseases associated with atherosclerosis . Thus, in a large clinical program conducted 18 GALAXY multicenter randomized controlled trials using statins to study the relationship between optimal control of lipids, atherosclerosis, cardiovascular morbidity and mortality [13].

The study was divided into three broad categories: 1) study the effect of rosuvastatin on lipids and inflammatory markers : COMETS, DISCOVERY, ECLIPSE, EXPLORER, LUNAR, MERCURY I, MERCURY II, ORBITAL, POLARIS, PULSAR, STELLAR; 2) study the effect of rosuvastatin on atherosclerotic coronary and carotid arteries : ASTEROID, METEOR, ORION; 3) study the effect of rosuvastatin on the risk of cardio - vascular complications, cardio - vascular and total mortality : AURORA, CORONA, JUPITER.

During the program GALAXY been shown rosuvastatin benefits in normalizing lipid metabolism, markers of inflammation and regression of atherosclerosis in the coronary and carotid arteries.

A randomized, double-blind, placebo- controlled study evaluated the JUPITER whether rosuvastatin therapy reduces (20 mg / day ) versus placebo fixed rate of cardiovascular events [ 24]. It was shown positive effect of rosuvastatin on prognosis in patients with existing CVD, reducing morbidity and mortality in patients associated with cardio - vascular events. In the analysis of 15 548 patients participated in the study JUPITER, found that the incidence of cardiovascular events among those receiving rozuvastatin decreased by 55% and LDL levels were < 1.8 mmol / l. In this study rozuvastatin proved the effectiveness of the drug for primary prevention of cardio - vascular complications. In addition to proven hypolipidemic action rozuvastatin has many other therapeutic properties, so-called " pleiotropic effects " [25 ]. Rozuvastatin normalizes endothelial function, which is caused by the normalization direct influence on the endothelium. Rozuvastatin inhibits platelet aggregation by altering cholesterol in their membrane and lowers izoprostanoids, which are markers of oxidative stress and strong activator of platelets. Rozuvastatin inhibits the expression of plasminogen activator inhibitor -1 on the surface of smooth muscle cells and increases the expression of tissue plasminogen activator on the surface of endothelial cells, and this effect is dose-dependent. Available antithrombotic properties is extremely important because the main cause of mortality in CVD are just manifestations of atherothrombosis.

It has been shown that the main factor of acute coronary syndrome in the majority of cases are " unstable " atherosclerotic plaques , which contain a large number of inflammatory cells. With this in mind , a special value are studies on the effects of statins on inflammation. Thus, it was shown that rozuvastatin reduces a leukocytes adhesion to the endothelium in response to the impact of proinflammatory mediators ( platelet activating factor , leukotriene B4 ).

Sign  in Ukraine, rosuvastatin and successfully applied over the past few years. The emergence of rosuvastatin gives reason to believe that it is an effective agent for the treatment and prevention of CVD. Also, due to the emergence of generic drug use became available to a wide range of patients. Rosuvastatin is a full- doses (5, 10, 20 and 40 mg) , which facilitates the selection of the dose and the drug in different clinical situations , increasing patient adherence to treatment. Thus, rosuvastatin is a highly effective and safe drug for primary and secondary prevention of CVD.

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