Vol 20, No 10 (2018)

Interview with S.V.Nedogoda and O.D.Ostroumova

The article presents a review of present data on pharmacogenetics role in statins pharmacokinetics and pharmacodynamics, their lipid-lowering activity and toxicity. The influence of genetic polymorphism of metabolizing ferments CYP3А4/5 and CYP2С9 on statins pharmacokinetics and effectiveness is shown. The influence of transporters (ОАТР and АВС families) on lipid-lowering activity and toxicity, particularly on confirmed association of SLCO1B1 polymorphism on statins pharmacokinetics as well as on risk of statin induced myopathy development after simvastatin or atorvastatin use that was reported in Food and Drug Administration guidelines is demonstrated. Р-glucoprotein and ABCG2 transporters also influence statins clinical effectiveness. The incidence of genetic polymorphism in Russian population is quite high, especially in OATP and ABC transporters, that can explain the use of medications in lower dosage than it is recommended for clinical practice. That is why the approaches for medication choices and dosage should be individualized for statin therapy optimization taking into account pharmacogenetic aspects.

Chronic heart failure is the modern epidemic. The article discusses the use of antagonists of mineralocorticoid receptors as drugs that improve the survival and quality of life of patients with chronic heart failure, discusses the possible complexity of the appointment, the ways to overcome them, the choice of a particular drug and the possibility of increasing patient adherence to treatment.

Objective: to assess the effect of nicorandil on the quality of life and on the long-term outcomes in patients with cardiac insufficiency of ischemic etiology. Materials and methods. The evidence base of nicorandil is analyzed. In a long-term out-patient observation, 175 people with a combination of coronary heart disease and heart failure, who were additionally assigned to nicorandil, were included in the Clinic-Diagnostic Center №4 in Moscow. They determined the incidence of anginal attacks, changes in the functional class of heart failure, and changes in the quality of life. Results. The follow-up was 13 months. The number of patients with I functional class increased by 45%, with III functional class decreased by 38%. In 71% of patients, the need for short-acting nitrates decreased. The connection between the reception of nicorandil and the improvement of the quality of life was revealed, and the tolerance to loads was increased. The degree of adherence to treatment was studied. Conclusion: the additional use of nicorandil to the main antianginal therapy improves the quality of life of patients with heart failure and coronary heart disease and has a positive effect on long-term outcomes.

Atrial fibrillation (AF) is the most common cardiac arrhythmia requiring treatment, which affects 2-3% of the adult population. AF leads to an increased risk of stroke 5 times, heart failure 3 times, dementia and lethality 2 times. Treatment can significantly reduce this risk. An important issue of treatment is the restoration of sinus rhythm in the paroxysm of AF and the provision of planned antiarrhythmic therapy. Antiarrhythmic drug 1C of the class of propafenone is an effective and safe drug for pharmacological cardioversion and routine antiarrhythmic therapy for the prevention of recurrent AF in patients without serious cardiac damage.

At present cardiac medications occupy an important place among polypills. According to European Society of Hypertension and European Society of Cardiology 2013 guidelines on hypertension treatment either free or fixed (preferable) combinations of two, three or more antihypertensive drugs are applicable at present. It should be noted that fixed combination has some advantages compared to a free one, especially in patients' compliance, that in its turn will contribute to cardiovascular risk reduction. It allows to reach target blood pressure (BP) level, has simple administration, dose titration and dosage regimen, and eliminates the risk of irrational combinations use. Also counter-regulatory mechanisms blockade is quite important: when fixed combination of drugs of different groups is used these medications can compensate adverse effects of each other, for example reduce edema that develops secondary when calcium channel blocking agents are used. Dosage regimen and titration are key stages in clinical practice. Fixed combination amlodipine + indapamide + perindopril has the greatest "flexibility" among triple fixed combinations. Advances of triple combination amlodipine + indapamide + perindopril use were studied in many randomized controlled trials. ADVANCE trial demonstrated effectiveness of triple fixed combinations use in all-cause mortality decrease of 14%, as well as cardiovascular mortality decrease of 28% compared with 5% in patients who received double therapy (р=0.02). PIANIST study showed high treatment compliance and effective BP reduction: target BP was reached in 72% of patients. Therefore, a lot of various polypills exist at present that allows clinicians to increase therapy effectiveness with the use of rational drug combinations and patients' compliance increase.

Postoperative cognitive dysfunction is a kind of transient or persistent brain impairment affecting the higher functions of the nervous system (attention, memory, etc.) that is observed in the postoperative period. It reflects changes in the functional and morphological state of the brain mainly of vascular genesis. The article presents the features of the main methods used to diagnose this condition in patients after cardiosurgical interventions. Methodological problems associated with the selection of the optimal set of scales for neuropsychological testing are considered. The advantages and disadvantages of neurophysiological methods, such as electroencephalography and recording of evoked cognitive potentials, are analyzed. Attention is paid to the methods of neuroimaging in the assessment of brain functions - various regimes of standard and functional magnetic resonance imaging, computed tomography (including single-photon emission tomography), positron emission tomography, etc. A relationship between the nature of the findings using these techniques and the results of neuropsychological testing, as well as the dynamics of the revealed changes in the postoperative period. The prerequisites for further research are given.

Diabetes mellitus should be regarded as a medical condition that exists in the context of comorbidity, where on the one hand diabetes itself facilitates comorbid pathology development, and on the other hand comorbid pathology influences its course, treatment tactics and clinical results. Diabetes is presented in European guidelines on stroke treatment and prevention and in European guidelines on ischemic heart disease treatment and prevention not only as risk factor for these conditions development but also as pathology that influences prognosis. Besides, data that allowed to consider DM as a risk factor for embolic complication were reported. Along with hypertension, congestive heart failure, atherosclerotic vascular disease, age and gender, diabetes was included in widely used scale CHA2DS2-VASс as pathology that defines embolic stroke probability and necessity for anticoagulant therapy. According to 2014 European guidelines on pulmonary artery thromboembolia treatment and prevention, type 2 diabetes mellitus is associated with risk of pulmonary embolism development. Moreover, in patients with already developed pulmonary embolism the presence of DM increases mortality by 5 times. A clear connection of glycemia control with risk of micro- and macrovascular complications development decrease is shown, wherefore better compensation of carbohydrate metabolism disturbances became the main treatment course. In concurrence with this it is suggested to establish individual treatment goals depending on patient's age, expected lifetime, severe complications development and severe hypoglycemia risk. For achieving these goals systematic control of glycated hemoglobin level and timely therapy management are necessary. Glucose level self-control is an essential component of diabetes full metabolic compensation achievement, the importance of which cannot be overemphasized. Self-control use allows to control glycemia more accurately, gives the physician information on treatment effectiveness, allows patients to be actively involved in the treatment process, forms their responsibility for its results, and encourages compliance with the recommendations. It is recommended to use individual glucometers with characteristics regulated by ISO 15197:2013 standard for the purpose of glycemia self-control.