Vol 21, No 10 (2019)

Aim. To provide data on main clinical and pharmacological parameters of angiotensin converting enzyme inhibitors (ACE inhibitors). Materials and methods. A review of national and foreign publications in the main search engines (PubMed, eLibrary, etc.) for the period 2000-2019 was conducted. Results. Prevention and effective treatment of cardiovascular diseases are a priority area of modern cardiology. Cardiovascular disease remains the leading cause of death worldwide. Arterial hypertension (AH) occupies the leading position among cardiovascular diseases, it is characterized by a severe progressive course, leads to other cardiovascular disorders, including chronic heart failure and chronic kidney disease, and also causes difficulties in the selection of therapy. The review presents data on the mechanism of action and clinical and pharmacological properties of ACE inhibitors, the main class of antihypertensive drugs, that affect the main link of pathogenesis of hypertension and cardiovascular complications, the renin-angiotensin-aldosterone system. This group of drugs has demonstrated a high efficacy at different stages of cardiovascular pathology in numerous clinical studies. The article presents a brief description of third-generation ACE inhibitor fosinopril, as well as the results of foreign and national studies proving its effectiveness and safety in patients with hypertension, chronic heart failure and chronic kidney disease with concomitant diabetes mellitus. The main difference between fosinopril and other ACE inhibitors is the dual route of elimination. This allows us to recommend the drug to patients with liver and kidneys disorders, as well as to elderly people without adjusting the dosage regimen and monitoring pharmacotherapy.

Risk stratification of coronary events in 5 years performed at the basis of available non invasive stress tests helps in the choice of management tactics. Revascularization has a significant prognostic impact not only for high risk patients. As in patients with ischemic heart disease (IHD) heartbeat rate more than 70 per minute is an independent predictor of myocardial infarction development, high heartbeat rate is one of the therapeutic targets in secondary prevention. Blood pressure control in patients with arterial hypertension and IHD is also important as 25% of population risk of myocardial infarction development is determined by arterial hypertension. The advantage of low (75-150 mg) and medium (160-325 mg) doses of acetylsalicylic acid (ASA) in atherothrombotic complications prevention in patients with stable IHD has been proven. Enteric coating prolongs ASA release and absorption. Unlike simple ASA, only after repeated daily use of gastro-resistant tablets platelet cyclooxygenase acetylation is cumulated and results in sufficient decrease of its activity at the 6th day that results in significant inhibition of platelet function. Dyslipidemia correction and lipid profile parameters maintenance at target levels throughout lifetime significantly decrease cardiovascular mortality as a result of secondary prevention in all age groups both in males and females. If the target level of low density lipoproteins is not reached on statins use they can be combined with ezetimibe that inhibits cholesterol absorption in intestine. In patients with persisting high levels of low density lipoproteins despite adherence to a diet and use of as high as possible statins doses, use of medications from the group of PCSK9 inhibitors is indicated. The use of monoclonal antibodies to interleukin-1 р (canakinumab) in patients with stable IHD with C-reactive protein level more than 2 mg/l showed the importance of inflammation in development of atherosclerosis and its complications. Although suppression of body ability to develop inflammatory processes is highly effective in cardiovascuar events prevention if systemic inflammation is present, their use is unlikely to become routine in all patients groups as treatment with canakinumab was associated with increase of fatal infectious complications. It is recommended to patients with IHD to perform seasonal flu vaccination. For those who seek medical advice in first 2 days after flu symptoms development it is reasonable to use antiviral medications. Chronic inflammation as a key element of atherosclerosis pathogenesis can be associated not only with infectious and immune but also with metabolic factors that requires improvement of other organs and systems health, change of behavior and lifestyle.

The current problem of public health is the optimization of drug therapy in patients with chronic heart failure and hypertension. Torasemide expands the use of loop diuretics in complex antihypertensive therapy due to a safe metabolic profile and multifactorial antihypertensive action. An urgent public health problem is the optimization of drug therapy in patients with chronic heart failure and arterial hypertension. Currently, the main indication for loop diuretics is chronic heart failure (CHF). The advantages of the torasemide loop diuretic compared to furosemide include: 1) torasemide is 4 times “stronger” in dosage; 2) a more stable (predictable) bioavailability, independent of food intake and the condition of the intestinal wall (relevant for congestive heart failure); 3) the half-life of torasemide (T1/2) is 4 times higher; 4) in chronic renal failure, T1/2 does not change (metabolism in the liver 80%); 5) additional effects of torasemide on renin-angiotensin-al-dosterone system - angiotensin II and aldosterone receptors. Due to its safe metabolic profile and multifactorial antihypertensive effect, torasemide expands the possibilities of using loop diuretics in complex antihypertensive therapy. The presence in the arsenal of the practitioner of the most famous drug torasemide allows optimizing drug therapy in patients with heart failure and arterial hypertension.

Aim. To provide up-to-date data on the feasibility, effectiveness and safety of prescribing ASA with the aim of primary prevention of cardiovascular and oncological diseases. Materials and methods. To write this review, a search was conducted for domestic and foreign publications in Russian and international search systems (PubMed, eLibrary, Medscape, etc.) for the last 0.5-11 years. The review included articles from peer-reviewed literature. Results. It is recommended that 75-100 mg of ASA be prescribed to patients with established cardiovascular diseases (CVD) and a 10-year risk of myocardial infarction in excess of 20%. The question of the appropriateness and safety of prescribing ASA in people with moderate and low risk remains open. Many experts oppose the prescription of ASA in these patients, citing the high risk of hemorrhagic complications and the lack of a positive effect. The risk of bleeding does not depend on the dose directly, which requires further study of the effectiveness of different dosages of ASA, depending on body weight. However, when prescribing an ASA, it is important to consider the gender, age, body weight of the patient, and the co-morbidity. There are numerous opinions about the benefits of prescribing ASA in people at low risk, including with regard to the antineoplastic effect. Conclusion. Based on the results of numerous studies, the question of the feasibility of primary prevention of CVD and colorectal cancer is ambiguous and requires further study.

Aim. To provide a scientific review of current data on pharmacogenetic aspects of antithrombotic therapy with warfarin. Materials and methods. To write this review we conducted searching for domestic and foreign publications in Russian and international search systems (PubMed, eLibrary, etc.) since 2000. Results. In recent years a social and economic relevance of thrombotic complications in patients with cardiovascular diseases is steadily increasing. The major drugs for long-term, in some cases life-long, thromboprophylaxis are oral anticoagulants. Despite the appearance of novel direct acting oral anticoagulants on the pharmaceutical market, vitamin K antagonist warfarin does not lose its position. In a number of clinical situations this drug has no alternative. Disadvantages of warfarin include its narrow therapeutic index and therefore the need for careful continuous laboratory monitoring of the blood coagulation system. An overdose of warfarin can cause serious bleeding complications which develop more often at the beginning of treatment. For this reason, a personalized approach to selecting the initial warfarin dose is of particular importance. When selecting the drug dose along with clinical factors genetic ones are also of great importance. The presence of genetic polymorphisms in genes that control warfarin pharmacokinetics and pharmacodynamics can be decisive. Warfarin dosing algorithms are available, however, new data that are recently emerging, dictate the need for their modification, including taking into account ethnic characteristics of patients. Different ethnic groups have features in a contribution of various genes and genetic polymorphisms to manifestation of warfarin’s anticoagulant effect. It was shown that identification of CYP4F2 genetic polymorphisms in African- Americans is not necessary, whereas for Europeans it is a prerequisite. At the same time, determining genetic variants of CYP2C rs12777823 is important for African Americans, but it should not be determined for Europeans. Conclusions. Warfarin remains one of the most commonly prescribed anticoagulants in routine clinical practice. Its safety is ensured by individual selection of initial and maintenance doses by use of algorithms based on clinical and genetic factors. The emergence of new data on warfarin pharmacogenetics allows to personalize the drug dosing to the maximum, which ensures the efficacy and safety of anticoagulant therapy.

Arrhythmia treatment is one of the most difficult problems in cardiology. The lack of evidence base determines the difficulty of choosing an antiarrhythmic drug (AAP) in a particular clinical situation, does not allow to fully assess the need and safety of treatment. The analysis of key studies on antiarrhythmic therapy (AAT). Detailed information on the properties, indications, contraindications, efficacy and safety of drugs widely used in Russian clinical practice, which include propafenone, amiodarone, sotalol, lappaconitine, is presented. A practical approach to the choice of AARP in various types of arrhythmias in patients without and with a pronounced organic lesion of the heart to which with regard to AAT include: unstable ischemic heart disease, myocardial infarction, low left ventricular ejection fraction <40% and left ventricular hypertrophy >15 mm. The special role of propafenone having 2 forms of oral and infusion has been analyzed. Having an evidence base makes it possible to use this drug to treat a wide range of arrhythmias, in particular, to relieve paroxysmal atrial fibrillation by the patient ("pill in pocket"), by outpatient physicians, emergency medical team and hospital in patients without pronounced organic heart disease.

Aim. To provide a scientific review on an unfavorable effect of non-steroidal anti-inflammatory drugs (NSAIDs) on cardiovascular outcomes (high blood pressure (BP), myocardial infarction, stroke, heart failure, atrial fibrillation), which can be united by the term of “cardiotoxicity”. Outcomes and methods. To write this review we searched for publications in Russian and international search engines (PubMed, eLibrary, etc.) since 1993. The review is based on an analysis of large clinical and observational studies and meta-analyzes, which is of great importance in the evidence of the data. Results. NSAIDs are widely used drugs in clinical practice. Along with the well-known gastrointestinal side effects of NSAIDs, a large group of adverse effects are cardiovascular events, which were referred to as “cardiotoxicity” in the 2000s. It was shown that cardiotoxicity of NSAIDs can be determined by the degree of selectivity to the action of cyclooxygenase (COX) -2 and has a dose-dependent and course effect for many drugs. According to a number of meta-analyzes and large clinical and observational studies (registers), the use of NSAIDs can lead to an increase in blood pressure (more than 5 mm Hg) and arterial hypertension (from 10 to 29%), and also counteracts the hypotensive effect of antihypertensive drugs ( p-blockers, angiotensin-converting enzyme inhibitors, calcium antagonists). According to large meta-analyzes, NSAIDs increase the risk of myocardial infarction, stroke, decompensated heart failure, atrial fibrillation, and mortality. These risks are showen both for selective COX-2 inhibitors - coxibs (rofecoxib, etoricoxib) and traditional non-selective NSAIDs (diclofenac, ibuprofen, indomethacin). However, celecoxib has an advantage of reducing the risk of cardiovascular outcomes over other NSAIDs. The unfavorable effect of NSAIDs on cardiovascular outcomes increases with doses or frequency of administration and is seen even with short-term use (less than 7 days), and also increases with high cardiovascular risk. Conclusions. The results of this review showes that in clinical practice there is no obvious safe therapeutic window for NSAIDs, that justifies the need for limited use of NSAIDs, especially in patients with established cardiovascular disease.