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Rhabdomyolysis is a very rare and most severe form of statin-induced muscle adverse event characterized by muscle pain, muscle necrosis with myoglobinemia and/or myoglobinuria with a very high risk of acute kidney injury and death. The article presents a case report of developing rhabdomyolysis in a middleaged female patient with hypertension, decompensated type 2 diabetes and albuminuria. A 60-year-old woman was admitted to the hospital for emergency indications with complaints of severe muscle weakness that began in the neck, which spread over several days to the upper and lower extremities, with a symptoms progression up to paresis. According to the appointment of a primary care physician, three months before hospitalization, the patient was switched from therapy with European generic brand-name rosuvastatin 20 mg to the Russian generic unbranded atorvastatin in the same dose (20 mg), which is not comparable in lipid-lowering effect. In a laboratory study, an increase in creatine phosphokinase level by 348 times (50462 U/L) of upper normal limit in combination with severe hypokalemia 1б7 mmol/L in the absence of renal dysfunction was recorded. Cancellation of statin, metformin and empagliflozin, intensive infusion therapy and treating electrolyte imbalance made it possible to prevent the development of acute renal damage, life-threatening arrhythmias and completely stop muscle complaints within a few days. The patient was discharged from the hospital on the 23rd day with reference clinical and laboratory values, including creatine phosphokinase.This case emphasizes the importance of maintaining clinical suspicion regarding rhabdomyolysis in patients receiving statin therapy in the presence of risk factors (in this case, female sex, hyperglycemia, chronic kidney disease, concomitant therapy), as well as the relevance of timely diagnosis and treatment of this condition.

Russian Experts’ Consensus on Metabolic Syndrome Problem in the Russian Federation: Defenition, Diagnosis Criteria, Primary Prevention and Treatment.

The evidences for statin use in cardiology are presented. Especially hypolipidemic efficacy of atorvastatin is demonstrated in according to comparative studies. Results of clinical studies on atorvastatin efficacy and safety in different groups of patients are also presented.

Aim. To evaluate quality of life changes and compliance to therapy in patients following successful transluminal angioplasty, who have indications for fluvastatin extended release in addition to standard treatment.Material and methods. This is a national observational multicenter study. An inclusion of 60 investigator centers is planned (out-patient medical centers), the total number of patients to be included is 600. Patients (men and women) with coronary heart disease following successful transluminal coronary angioplasty, who were prescribed fluvastatinextended release (Lescol Forte, Novartis) 80 mg once daily will be included in the observation. The following efficacy and safety parameters will be evaluated: quality of life assessed with SF-36 scale before and during treatment; compliance to therapy; adverse events and serious adverse events. Observation period is planned for 6 months. During this period patient is expected to make 4 visits to treating physician. According to the physician’s decision, observation period can be extended to 12 months.Present study status. The study is completed. 524 patients completed the observation, including 116 patients who were followed up for 12 months. There are 414 men (79%) and 110 women (21%) among patients enrolled into the study.

Aim. The main aim of the present study was to evaluate quality of life changes and compliance to therapy in patients following successful transluminal angioplasty, who were prescribed fluvastatin extended release in addition to standard treatment.Material and methods. This was a national prospective multicenter observational study. Patients with coronary heart disease following successful transluminal coronary angioplasty, who were prescribed fluvastatin extended release (Lescol Forte, Novartis) 80 mg QD were included in the present observation. The following efficacy and safety parameters were evaluated: quality of life evaluated with SF-36 scale before and during treatment; hypolipidemic efficacy, compliance to therapy; adverse events and serious adverse events. Observation period was 6 months in all patients and 12 months in some patients at the discretion of the investigator.Results. 524 patients (79% men and 21% women) completed the 6 months observation period and 116 patients were followed up for 12 months. Significant increase of all measures of SF-36 scales, physical and mental health was observed in 6 and 12 months of fluvastatin extended release treatment. Total and low density lipoprotein cholesterol reduction was 30.5% and 54.9% respectively, p

The evidence base of statin therapy in primary and secondary prevention of ischemic stroke is surveyed. Results of classical trails with statins in ischemic stroke prevention as well as results of meta-analyses are discussed.

The high prevalence of persistent dyslipidemia in primary and specialized care patients treated with statins justifies the need to identify its reasons and develop the recommendations on the treatment optimization. At present, Russian studies focusing on the achievement of target lipid levels remain scarce, which emphasizes the importance of the problem and its further investigation. Aim. Cross-sectional epidemiological study which assessed the prevalence of persistent dyslipidemia in statin-treated patients and analysed the predictors of the achievement of target lipid levels. Material and methods. The lipid profile parameters were analysed in 1586 statin-treated out-patients with varied levels of cardiovascular risk, taking into account the type of lipid-lowering therapy and its doses. The assessment of the cardiovascular event (CVE) risk and the definition of target levels of low-density lipoprotein cholesterol (LDL–CH), as well as normal levels of triglycerides (TG) and high-density lipoprotein cholesterol (HDL–CH), was based on the clinical recommendations by the European Society of Cardiology (ESC 2007) and by the European Society of Cardiology and the European Atherosclerosis Society (ESC/EAS 2011). Results. The analysis based on the ESC 2007 recommendations has demonstrated that the target levels of LDL–CH (

Aim. To assess the effects of original statins as monotherapy or in combination with ezetimibe on the levels of proinflammatory cytokines and high-sensitive C-reactive protein (hsCRP) in patients with coronary heart disease (CHD) and hyperlipidemia (HLP). Material and methods. The study included 60 male and female patients with CHD, primary polygenic HLP, and the levels of low-density lipoprotein cholesterol (LDL-CH) of 2,9-4,9 mmol/l. Monotherapy with original statins or ezetimibe lasted for 6 months, while the combination therapy lasted for 3 months. In all randomised patients, the levels of hsCRP, interleukin 6 (IL-6), and monocyte chemotactic protein-1 (MCP-1) were measured at baseline, 12 and 24 weeks after the therapy started. Results. At baseline, median hsCRP levels in the groups of Ezetrol, Zocor, Liprimar, and Crestor monotherapy were 0,5-0,88 mg/l, with no significant dynamics after 3 months of the treatment. Baseline IL-6 levels across the monotherapy groups were 1,94-2,54 pg/ml; at 3 months, there was a non-significant reduction by 7-32 %. After 3 months of the therapy, the decrease in MCP-1 levels was not statistically significant (-1,3-7,7 %). The combined therapy did not result in a significant dynamics of hsCRP concentrations, with the exception of the group receiving Ezetrol and Liprimar. Although the combined therapy further reduced MCP-1 levels (by 30-78 pg/ml), these changes were not statistically significant. No significant difference was observed across statin and Ezetrol groups in terms of their effects on IL-6 and MCP-1 levels. Conclusion. The comparison of the three treatment schemes demonstrated similar, but not statistically significant reduction on the levels of hsCRP, IL-6, and MCP-1. No marked benefits were observed for either monotherapy or combination therapy over 12-24 weeks of the follow-up.

HMG-CoA inhibitors have been widely used in primary and secondary prevention of atherosclerosis for more than 30 years. The evidence base for statins includes dozens of randomized clinical trials (RCT), involving hundreds of thousands patients. According to the results of the latest meta-analyses, reducing low-density lipoprotein cholesterol (LDL-CH) level by 1 mmol/l in statin-treated patients could decrease cardiovascular risk by 0,8 %. Atorvastatin (Liprimar®) is a modern synthetic statin, which has been thoroughly studied in several RCTs over the last 15 years. These trials demonstrated its effectiveness and tolerability in patients with chronic coronary heart disease, acute coronary syndrome (ACS), Type 2 diabetes mellitus, and arterial hypertension. In the studies comparing atorvastatin (10-80 mg/d) to other statins, baseline LDL-CH levels were reduced by 53 % in atorvastatintreated patients. Atorvastatin therapy was also well tolerated. Compared to placebo, atorvastatin therapy in the dose of 10 and 80 mg/d was associated with the incidence of hepatic transaminase elevation of 0,1 % and 0,6 %, respectively. This evidence base (in particular, the results of the trials on 80 mg/d atorvastatin therapy in ACS patients) has been a cornerstone of modern clinical guidelines, recommending target LDL-CH levels of 2 mmol/l. Currently, atorvastatin is the most widely prescribed statin in the majority of both developed and developing countries. Increasing initial dose and prescribing high-dose atorvastatin therapy (40-80 mg/d) could facilitate an improvement in treatment quality and a reduction in high levels of cardiovascular mortality inRussia.

Aim. To study the lipid-lowering effectiveness, as well as the effects on inflammatory markers and vascular wall function, of ezetimibe as monotherapy and in combination with initial doses of original statins (simvastatin, atorvastatin, and rosuvastatin). Material and methods. The study included 60 male and female patients with coronary heart disease and hyperlipidemia. Mean age of the participants was 61,4 years; mean baseline level of low-density lipoprotein cholesterol (LDL-CH) was 4,1 mmol/l. The participants were randomised into four groups: ezetimibe monotherapy (10 mg/d) for 24 weeks, or statin monotherapy (simvastatin, atorvastatin, or rosuvastatin; 10 mg/d) for 12 weeks with following assessment of LDL-CH levels. If target levels were not achieved on statin monotherapy, a combination of ezetimibe and statins was administered for the next 12 weeks. The effects of monotherapy and combined therapy on lipid profile, C-reactive protein, pro-inflammatory cytokines, vascular elasticity and stiffness, as well as treatment tolerability, were assessed. Results. After 3 months of the treatment, LDL-CH levels in statin monotherapy groups decreased to 2,66-2,98 mmol/l. The decrease in LDL-CH concentration in ezetimibe group (-16,4 %) was significant. After 3 months, the percentage of the patients with achieved target LDL-CH levels was 17 % for ezetimibe, 42 % for simvastatin, 31 % for atorvastatin, and 58 % for rosuvastatin. After 6 months, the patients receiving combined therapy demonstrated LDL-CH reduction by 39,5-50,6 %. From Month 3 to Month 6, the additional lipid-lowering effect of ezetimibe, as a part of combined therapy, varied from 13 % to 25,9 %. Conclusion: Adding ezetimibe (10 mg/d) to any statins reduces LDL-CH levels by extra 20-30 %. Combined therapy was required in over 50 % of the patients. Therefore, the response to statin monotherapy is not universal and in one-third of the patients could be regarded as poor. In these individuals, the “double inhibition” approach (combining statins with ezetimibe 10 mg/d) could control LDL-CH levels more effectively.

The increased level of low-density lipoprotein cholesterol (LDL-CH) is one of the risk factors (RFs) of coronary heart disease and atherosclerosis. Statins, with their vast evidence base on mortality reduction, are the principal medications in atherosclerosis treatment. The results of the recent controlled studies on CH reduction justified the decrease in target lipid levels: for LDL-CH — 2 mmol/l or less. Double CH inhibition is a new concept in plasma CH reduction by 50%, due to synthesis blockage (statins) and reduced intestinal reabsorption of dietary and biliary CH. The clinical trials of a fixed-dose combination Inegi ® (Ezetimibe / simvastatin) demonstrated its high effectiveness in achieving new target levels of LDL-CH, as well as good tolerability and safety, compared to statin monotherapy. The ongoing clinical trial IMPROVE-IT, assessing the effects of double CH inhibition on cardiovascular mortality, will clarify the role of Ezetimibe® and Inegi® in the treatment of dyslipidemia and atherosclerosis.

Aim. To study atorvastatin (10 and 20 mg/d) effects on lipid, C-reactive protein, and fibrinogen levels, vascular wall structure and function in patients with coronary heart disease (CHD) and primary hyperlipidemia (PHL). Material and methods. In total, 50 CHD and PHL patients were randomized into two stable-dose atorvastatin groups (10 or 20 mg/d) for 24 weeks. Atorvastatin effects on lipid levels, endothelial function, vascular wall distensibility and stiffness, as well as treatment tolerability, were examined. Results. Twenty-four-week atorvastatin therapy (10 or 20 mg/d) reduced low-density lipoprotein cholesterol (LDL-CH) level by 34,9% and 43,9%, respectively (p

Aim. To compare effects of atorvastatin in the doses of 10 and 20 mg/d on lipid profile, C-reactive protein (hsCRP), fibrinogen levels, as well as vascular wall structure and function in patients with coronary heart disease (CHD) and primary hyperlipidemia (PHL). Material and methods. Fifty CHD and PHL patients were randomized to 10 or 20 mg/d atorvastatin doses (no titration), for 24-week period. Atorvastatin effects on lipids, treatment tolerability (symptoms ± increased hepatic enzymes), as well as on endothelial function, vessel elasticity and stiffness, were examined. Results. After 24 weeks of 10 mg/d atorvastatin treatment, levels of total cholesterol (TCH), triglycerides (TG), and low-density lipoprotein CH (LDL-CH) significantly decreased – by 25,4%, 21,7%, 34,9%, respectively. In 20 mg/d group, these figures were 27%, 15,2%, and 43,9%, respectively. No significant inter-group difference in LDL-CH levels was registered. No substantial CRP and fibrinogen level reduction was observed. During 24 weeks, 7 adverse events were registered, only 2 (4%) being related to atorvastatin therapy. Conclusion. In patients with CHD and PHL, atorvastatin (10-20 mg/d) decreased LDL-CH levels by 35-44%, and was well-tolerated. The therapy did not affect hsCRP and fibrinogen levels.

Various clinical forms and complications of atherosclerosis remain the leading causes of morbidity and mortality in both developed and developing countries. HMG-CoA reductase inhibitors (statins) are the key components of pharmaceutical treatment in patients with dyslipidemia (DLP) and atherosclerosis. Statins have been thoroughly studied not only in randomised clinical trials with “hard” end-points, but also in the so called regression studies. The latter tested the hypothesis of qualitative and quantitative changes in coronary arteries (CA) due to aggressive reduction (-40-50% from baseline) of low-density lipoprotein (LDL) cholesterol levels. The results of the first regression studies justified the increase of statin doses in clinical practice, as well as led to large randomised clinical trials of statin therapy. In current regression studies, vascular atherosclerosis is monitored using such methods as intima-media thickness assessment, magnetic resonance imaging, and intravascular ultrasound. Reduced progression of carotid atherosclerosis (METEOR Study, rosuvastatin 40 mg/d; ENHANCE Study, ezetimibe 10 mg/d plus simvastatin 20 mg/d) and CA atherosclerosis (REVERSAL Study, atorvastatin 80 mg/d), as well as atherosclerosis regression (ASTEROID Study, rosuvastatin 40 mg/d), was demonstrated. Aggressive lipid-lowering effect (-40-50%), observed for high statin doses in modern regression clinical trials, was well-tolerated, with no severe adverse events. The results and principles of regression studies could be widely used in clinical practice, to optimise the treatment of severe DLP and atherosclerosis.

Atherosclerosis and it’s clinical implications (myocardial infarction, stroke, intermittent lameness) is a serious medico-social problem in Russia. Statins (or HMG-CoA reductase inhibitors) are the first-choice agents to prevent cardiovascular disease events. The paper presents the results of early regression studies and modern regression studies using MRI imaging concerning the regression or stabilization atherosclerosis and rationale and baseline characteristics of russian regression study “FREGAT”.

Abstract In the era of precision medicine, treatments that target specific modifiable characteristics of high-risk patients have the potential to lower further the residual risk of atherosclerotic cardiovascular events. Correction of atherogenic dyslipidemia, however, remains a major unmet clinical need. Elevated plasma triglycerides, with or without low levels of high-density lipoprotein cholesterol (HDL-C), offer a key modifiable component of this common dyslipidemia, especially in insulin resistant conditions such as type 2 diabetes mellitus. The development of selective peroxisome proliferator-activated receptor alpha modulators (SPPARMα) offers an approach to address this treatment gap. This Joint Consensus Panel appraised evidence for the first SPPARMα agonist and concluded that this agent represents a novel therapeutic class, distinct from fibrates, based on pharmacological activity, and, importantly, a safe hepatic and renal profile. The ongoing PROMINENT cardiovascular outcomes trial is testing in 10,000 patients with type 2 diabetes mellitus, elevated triglycerides, and low levels of HDL-C whether treatment with this SPPARMα agonist safely reduces residual cardiovascular risk.