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Rational Pharmacotherapy in Cardiology

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Vol 14, No 5 (2018)
View or download the full issue PDF (Russian)
https://doi.org/10.20996/1819-6446-2018-14-5

ORIGINAL STUDIES

636-645 374
Abstract

Background. Dyslipidemia is one of the most serious modifiable risk factors for acute coronary  syndrome which is the most leading cause of mortality and morbidity worldwide.

Aim. To assess the short-term safety and efficacy of full dose rosuvastatin and atorvastatin in patients with acute coronary  syndrome.

Material and methods. Single center, prospective, randomized study included 100 patients who were randomized from first 24-hour of admission to either atorvastatin 80  mg  daily (group 1) or rosuvastatin 40  mg  daily (group 2). Primary outcomes included levels of inflammatory markers (erythrocyte sedimentation rate [ESR], high-sensitive C-reactive protein [hs-CRP] and total leukocyte count [TLC]) after 4 weeks of treatment and lipid profile after 3 months. Secondary  outcomes included recurrent myocardial infarction, recurrent angina, stroke and side effects.

Results. At admission, both groups  were comparable in age, without statistically significant difference regarding risk factors (diabetes, hypertension, smoking and obesity), echocardiography (end-diastolic volume, end-systolic volume and ejection fraction), laboratory parameters of inflammation and lipid profile. After 1 month, there was insignificant difference between rosuvastatin and atorvastatin in the reduction of ESR, Hs-CRP or TLC. After 3 months rosuvastatin showed statistically significant reduction in the level of low-density lipoprotein cholesterol, triglyceride (p<0.001) and significant increase in high-density lipoprotein cholesterol (p<0.001) when compared to atorvastatin and at the same time the rosuvastatin group  was safer regarding liver enzymes elevation, p<0.001 for alanine and p<0.01 for aspartate aminotransferases, respectively.

Conclusions. Our findings demonstrated that  rosuvastatin 40  mg/day is safer and more effective than  the atorvastatin 80  mg/day in the terms  of lipid parameters and inflammatory biomarkers.

646-653 206
Abstract

Aim. To investigate arterial stiffness parameters in middle-aged patients with stage II grade 1-2 essential arterial hypertension (HT) and evaluate their changes after treatment with single pill combinations (SPC) of antihypertensive drugs.

Methods. At the first phase  of the study, according to the medical records data, a group of untreated patients with stage II grade 1-2  HT (n=100, 47 men, mean age 51.9±6.5 years), and a group of healthy controls with normal blood pressure (BP) (n=86; 28 men; mean age 48.8±5.8 years) were formed. The analysis of arterial stiffness was performed by the volumetric sphygmography technique using VaSera VS-1500N device (Fukuda Denshi Co., Ltd, Japan). All the subjects underwent ambulatory BP monitoring (BPLab, BP2005-01.04.00.2540, Petr Telegin, Russia) as well as a routine BP measurement by the Korotkov method. At the second  stage  of the study, a group of HT patients (n=90) was formed  according to the medical history data.  These patients thanks  to antihypertensive treatment with SPC (perindopril arginine/indapamide or valsartan/amlodipine) achieved the target BP level (<140/90 mm Hg) according to routine measurements and they were assessed in terms  of therapy efficacy (general clinical data, SMAD, volume sphygmography) 12 weeks after the target BP level was reached.

Results. At the first phase of the study, in HT patients cardio-ankle vascular index (CAVI), both on the left (7.9±1.3) and right side (8.1±1.3), as well as the right-side augmentation index (1.22±0.31%) were significantly higher (p=0.006, p=0.003, p=0.047, respectively) compared to the controls (7.5±0.9, 7.6±0.9, 1.13±0.28%, respectively). At the second  phase  of the study, after SPC treatment the CAVI significantly decreased both on the left- (up to 7.36±1.37, p=0.02) and right-side (up to 7.46±1.44, p=0.02).

Conclusions. In untreated 40-65 years-old patients with stage II grade 1-2 HT arterial stiffness assessed by volumetric sphygmography is significantly higher compared with sex-matched healthy individuals. 12-week therapy with SPCs improves the elastic properties of the major arteries, reducing the CAVI value. 

654-663 128
Abstract

Aim. To assess  the  relationship between pre-diabetes/type 2 diabetes mellitus (type 2 DM) and  long-term adverse  prognosis in patients with coronary  artery disease (CAD) who underwent coronary  artery bypass grafting (CABG).

Material and methods. 347 CAD patients who underwent CABG in the period from 2006 to 2009 were enrolled into the study. All patients were divided into 3 groups:  148 patients with type 2 DM (the median age – 58 years, the median follow-up – 1.8  years), 23 patients with pre-diabetes, i.e. impaired fasting glycemia and/or impaired glucose tolerance (the median age – 58 years, the median follow-up – 1.7  years); and 176 patients without diabetes and other carbohydrate metabolism disorders (CMD) (the median age – 58 years, the median follow-up – 1.7 years). The prognosis was considered as unfavorable in case of any major adverse  cardiovascular events  (MACEs) defined as myocardial infarction, stroke,  cardiovascular death. Logistic regression was used to identify the predictors of the unfavorable prognosis.

Results. All patients in the study groups were comparable in age (p=0.345) and the median of the follow-up (p=0.134). The comparative assessment of the long-term prognosis showed the similar rate of major adverse  cardiovascular events in the groups  with CMD (the diabetes group  – 14.2% vs the  pre-diabetes group  – 13.0%), compared to 6.3% in patients without any CMD (p=0.028 for the  groups  with DM and  without CMD). The regression analysis reported that type 2 DM appeared to be a significant factor associated with the development of the long-term MACEs (odds ratio [OR] 3.307, 95% confidence interval [95%CI] 1.372-7.968, p=0.007). The addition of pre-diabetes as a potential predictor of the unfavorable prognosis increased 3.6-fold the risk of long-term MACEs (OR 3.617; 95%CI 1.557-8.403, p=0.001).

Conclusion.  Pre-diabetes  significantly  affects  the  prognosis  of patients  after  CABG, similarly  to type  2 DM. The diagnosis  of CMD in  patients undergoing CABG is of significant clinical relevance.

664-669 181
Abstract

Aim. We aimed to compare effectiveness of new  class III antiarrhythmic drug  Refralon with direct current  cardioversion (DCC) in patients with persistent atrial fibrillation (AF).

Material and methods. 60  patients with persistent AF were  randomized to groups  of DCC (n=30) and  pharmacologic conversion (PCV; n=30). There were no differences in age, sex, AF duration, concomitant cardiovascular diseases, CHA2DS2-VASc score and echocardiographic parameters between the groups  compared. Initial assessment excluded contraindications to restore  sinus rhythm  (SR). In DCC group  two attempts using biphasic synchronized shocks of 150 J and 170 J were performed. In PCV group patients received up to three subsequent intravenous injections of Refralon 10 μg/kg (maximal dose 30 μg/kg).

Results. SR was restored in 27 of 30 patients (90%) in DCC group and in 28 of 30 patients (93.3%) in PCV group.  95% confidence interval (CI) for primary effectiveness criterion was [-0.1 – 0.16]. AF recurred in 1 patient after successful DCC. There were no AF recurrences in PCV group.  26 of 30 patients (86.7%) in DCC group  and 28 of 30 patients (93.3%) in PCV group  remained in SR 24 hours after cardioversion. 95%CI for secondary effectiveness criterion was [-0.07 – 0.19].

Conclusion. Effectiveness of Refralon is noninferior to DCC in patients with persistent AF.

670-677 286
Abstract

Aim. Comparison of different treatment tactics – medicated antiarrhythmic therapy (AAT) and radiofrequency ablation (RFA) of elderly and senile pa- tients with relapsing atrial fibrillation (AF) as more severe patients with a burdened comorbid background.

Material  and  methods. The study  included  108 patients  with  paroxysmal  and  persistent  AF who  were  in  hospital  and  then  under  outpatient observation for 2 years. Depending on the method of treatment, patients were divided into 2 groups: the group receiving medicated AAT (n=45) and the group  treated with RFA (63 patients). Most patients of the 2nd  group  (n=60) after  the RFA received AAT, i.e. so-called hybrid therapy. These groups  were comparable in age (mean age 64.9 and 64.7 years, respectively), sex and underlying pathology, comorbid diseases.

Results. In patients who received "hybrid" therapy after 2 years of observation, it was more often possible to preserve  the sinus rhythm and achieve a reduction in arrhythmia episodes in comparison with the  drug  group  (95.2% and  86.6%, respectively). Quality of life and  the  frequency of complications of AAT in these groups  of patients were comparable.

Conclusion: In elderly and senile patients with paroxysmal and persistent atrial fibrillation, RFA and hybrid therapy was more effective for maintaining sinus rhythm compared to drug therapy. After RFA in this category of patients, in most cases, medicated AAT was used. When choosing the tactics of rational AAT in elderly patients, preference should be given to tactics in which it is possible to achieve an improvement in the quality of life.

678-686 130
Abstract

Aim. To study the combined effect of cardiovascular risk factors and genetic markers that encode the proteins of the main components of neurophysiological systems (renin-angiotensin-aldosterone, sympathetic-adrenal systems, endothelial dysfunction) on the development of arterial hypertension among the indigenous and non-indigenous population of Mountain Shoriya.

Material and methods. We performed a clinical and  epidemiological study  of the compactly settled population in the remote areas  of Mountain Shoriya. This region of middle mountains is situated in the south of Western Siberia. We examined 1409 subjects (901 subjects – the representatives of indigenous nationality [the Shors], 508 subjects – representatives of non-indigenous nationality [90% among them  were the representatives of the European ethnicity]). Hypertension was diagnosed according to the National Guidelines of the Russian Society of Cardiology/the Russian Medical Society on Arterial Hypertension (2010). All patients underwent clinical, laboratory and  instrumental investigation. Polymorphisms of genes  ACE (I/D, rs 4340), АGT (c.803T>C, rs699), AGTR1 (А1166С, rs5186), ADRB1 (с.145A>G, Ser49Gly, rs1801252), ADRA2B (I/D, rs 28365031), MTHFR (c.677С>Т, Ala222Val, rs1801133) and NOS3 (VNTR, 4b/4a) were tested using polymerase chain reaction.

Results. Cardiovascular risk factors  associated with hypertension in cohort  of Shorians: hypercholesterolemia [Odds Ratio (OR) 1.54,  low density lipoproteinemia (OR 1.48), violation of carbohydrate metabolism (OR 1.53), obesity (OR 2.25), including its abdominal type (OR 1.53), the family anamnesis of early cardiovascular diseases (OR 1.88)]  and  rs4340 polymorphisms of the  ACE gene  (OR 4.39), rs5186 of the  AGTR1 gene  (OR 10.02); in the cohort of the non-indigenous ethnos – hypercholesterolemia (OR 1.87), hypertriglyceridemia (OR 1.87), obesity (OR 2.75), abdominal obesity (OR 2.73), family anamnesis of early cardiovascular diseases (OR 2.48), the polymorphism rs5186 of the AGTR1 gene (OR 26.77). Genotype G/G ADRB1 gene was characterized by protective effect against hypertension in the Shorians.

Conclusion. Evaluation of the complex influence of clinical and genetic factors  on the development of hypertension in the population of Mountain Shoriya showed their comparable importance among the indigenous population and  the predominance of non-genetic factors  among the non-indigenous population.

NOTES FROM PRACTICE

687-690 504
Abstract

The purpose of this article is to demonstrate a new approach to polypharmacy management in ambulatory practice using as example a case report  of adverse drug event (ADE) in patient with atrial fibrillation and comorbidity. The patient had excessive polypharmacy level (11 drugs). Minor bleeding developed when using these  drugs (INR – 6.70). The analysis of drug interactions was performed at patient’s home by online database "Multi-Drug Interaction Checker" and  "Time-effect-drug administration" graphic. As a result of analysis, it was  described two  drug  interactions led to minor bleeding: warfarin+rosuvastatin, warfarin+amiodarone. It was found that the patient had not taken rosuvastatin before and it was first-time administration of rosuvastatin. Therapy was corrected, the causes and effects of ADE are eliminated. The drugs without proven benefit and known drug interactions were cancelled. There were no clinical signs of bleeding after correction and the last INR was 2.54.

Combined using of "Multi-Drug Interaction Checker" and  "Time-effect-drug administration" graphic allowed to detect causal relationship between ADE and drugs initiating it and then to make a rational decision right at the patient’s home in a short time.

691-698 229
Abstract

Pericarditis is not enough researched and described in literature despite the emergence of a large quantity of up-to-date laboratory and instrumental methods of verification. The main problem is that  pericarditis might be a sign of many infectious and non-infectious diseases. It is quite difficult to define the etiopathogenetic reason of process. The article presents a clinical observation of a 53 years old mail patient with paroxysms of atrial flutter, non-symptomatic febrile fever, arthralgia and  signs of exudative pericarditis, which were  manifested after  the acute  viral infection. The symptoms have been lasting for 8 months before the patient’s hospitalization. In lab tests anemia, leucopenia, increase level of platelets and increase antinuclear antibody level were found. Several conceptions were considered: cancer with paraneoplastic syndrome, systemic disease, infectious process, myeloma, which were subsequently excluded. Due to the fact that pericardial effusion may often be associated with tuberculosis Diaskin test and T-SPOT were performed and they appeared to be positive. After several months of antituberculous treatment temperature normalized, atrial flutter episodes and arthralgia diminished. So empirically and  laboratory tuberculous pericarditis with atypical manifestation was  confirmed. The particularity of this observation is a nontypical clinical picture and the absence of a primary focus of infection. That is why the clinicians could not define the diagnosis rapidly.

699-702 190
Abstract

The considered clinical case of combination of multifocal atherosclerotic vascular lesion with type 2 diabetes mellitus and liver fibrosis demonstrates a combination of polyvalent risk factors  for resistance to antiplatelet therapy with clopidogrel. The decrease in the effectiveness of prolonged therapy with P2Y12  inhibitor was clinically manifested by repeated thrombotic events and was confirmed by laboratorial VerifyNow P2Y12  Assay test system as a low percentage of inhibition of ADP-induced platelet aggregation. We established probable genetic predictors of the decrease in the effectiveness of antiplatelet therapy in this patient, namely, the  carriage of polymorphic markers  of the  ABCB1 CT, CES1 CA and  CYP3A4*22 CT genes  that determine the decrease in absorption, excessive hydrolysis of the drug and reduced activity of isoenzymes and transporters, that leads to disorders of active clopidogrel metabolite formation. A potential contribution of hepatic dysfunction to reduction in antiaggregant effect of P2Y12 inhibitor was demonstrated. Variant of drug interaction of clopidogrel and an inhibitor/substrate of P450 CYP2C19 – omeprazole, accompanied by a decrease in the effectiveness of antiplatelet therapy, was also considered.

ASSOCIATED PROBLEMS OF CARDIOLOGY

703-710 180
Abstract

Rheumatoid arthritis (RA) is a disease with a high cardiovascular risk, which is caused, in particular, by an increased incidence of chronic heart  failure (CHF). Analysis of the results of the main studies on the prevalence of CHF, the features of the etiology and pathogenesis of myocardial dysfunction in RA was the purpose of the review. According to the registers, population and epidemiological studies, the risk of CHF and CHF-associated mortality in RA patients is 1.5-2.5 times higher than in the general population. In most of the studies only clinically manifested congestive heart  failure (HF) was considered, so the actual prevalence of CHF may be significantly underestimated. An increase in the risk of CHF was noted immediately after the debut of RA, with the prevalence of HF with preserved systolic function of the left ventricle, which indicates the important role of diastole disturbance in the pathogenesis of myocardial dysfunction. Chronic systemic autoimmune inflammation contributes to the  development of CHF in RA patients, in addition to coronary heart disease, traditional risk factors (TRFs) of cardiovascular diseases (CVD). Inflammation plays a leading role in the development of CHF through various mechanisms including direct damage to the myocardium and coronary arteries (myocarditis, coronary vasculitis, microcirculatory disorders), aggravation of the severity of TRFs of CVD, accelerated progression of ischemic heart  disease, endothelial dysfunction, increased vascular wall stiffness, cardiac and vascular remodeling. Early diagnosis of CHF and timely measures that can slow its progression is needed due to the high risk of CHF and CHF-associated mortality in RA patients, especially in patients with risk factors for CHF.

711-715 122
Abstract

Background. Patients with psoriatic arthritis (PsA) have increased risk of cardiovascular diseases (CVD). Anti-tumor necrosis factor (TNF) therapy is an effective in PsA but its cardiovascular effects are poorly understood.

Aim. To study the changes in carotid intima-media thickness (c-IMT), parameters of arterial stiffness (AS), ambulatory blood pressure monitoring (AMBP) in early PsA (EPsA) patients during the anti-TNF therapy with adalimumab (ADA).

Material and methods. Patients with EPsA (n=16; 11 females, 5 males; median age 45.5 years, EPsA duration – 7.7  months) were included into the study. All patients were treated with ADA 40 mg every other week up to 3 months. At baseline and after 3 months of therapy all patients were assessed  for conventional cardiovascular risk factors, DAS (Disease Activity Score) and  HAQ (Health Assessment Questionnaire) indices, C-reactive protein (CRP), c-IMT, ABPM. At baseline the  4 patients had  arterial hypertension, and  all patients received effective antihypertensive therapy. All patients were assessed for AS parameters: carotid-femoral pulse wave velocity (PWVcf) and index of wave reflection (rigidity index; RI, %). c-IMT was measured using a high-resolution B-mode ultrasound machine. The results are presented in the form of a median – Me (25; 75 percentiles).

Results. By the end of the 3rd month of therapy, a decrease in the activity of early PsA was observed as compared to baseline values: DAS decreased from 4.6 (2.9; 1.9) to 1.6 (1.3; 1.9), p=0,001; HAQ from 0.93 (0.81; 1.31) to 0.25 (0; 0.56), p=0,001; CRP from 27.2 (9.7; 33.7) to 1.8 (0.8; 3.1) mg/l, p=0.001. EPsA remission (DAS<1.6) was achieved in 94% of patients. By the end of therapy c-IMT decreased from 0.8 (0.74; 0.85) to 0.73 (0.58; 0.77) mm, p=0,01; as well as AS parameters: PWVcf from 9.9 (7.7; 17.7) to 9.2 (7.4; 10.6) m/s, p<0.05; RI from 69.5 (58; 74) to 49.5 (44; 64)%, p<0.05. AMBPs parameters didn't change significantly. We found significant (p=0.03) decrease in the frequency of the increase in 24-hour diastolic blood pressure.

Conclusions. Anti-TNF treatment with ADA improves arterial wall state by decreasing inflammation. These data confirm the idea that inflammation involves in acceleration of atherosclerosis in EPsA patients. 

PREVENTIVE CARDIOLOGY AND PUBLIC HEALTH

716-724 150
Abstract

Aim. To assess the economic burden associated with the absence of lipid-lowering therapy (LLT) in patients with cardiovascular diseases (CVD) and hypercholesterolemia (HCS) in the Russian population in 2016, including direct costs of the health care system  and indirect economic losses due to premature death, absenteeism and disability.

Material and methods. The calculation includes data  from local population-based studies (prevalence of HCS, treatment coverage and efficiency), as well as Russian statistics on CVD for 2016. Population attributive risk (PAR) was determined, which reflected the incidence of excessive morbidity associated with the lack of HCS therapy in developing CVD for the Russian population, based  on LDL cholesterol level. Direct and indirect components of economic burden associated with the absence of LLT have been calculated, as well as the number of deaths with the calculation of "lost years of potential life" lacking to reach the age of 72 years, and losses associated with premature mortality in the economically active age. Indirect costs (economic losses) included non-received gross domestic product (GDP) due to premature mortality and disability in economically active age and loss of earnings due to temporary disability (TD). To estimate the indirect costs,  the number of people of the working age  with permanent disability in each  of the disability groups  has  been  calculated. The indirect costs  due  to temporary disability were  calculated as payments of salary including for days  of incapacity for work multiplied by the number of days of TD according the Russian statistics data.

Results. The absence of LLT  in people with HCS increases the  risk of CVD related mortality by one  third, death due  to cerebrovascular diseases, including stroke,  by more than a half. PAR was estimated to be 17% for CVD mortality in general, 26% for cerebrovascular diseases. Contribution of HCS and  the  lack of LLT to morbidity is 29% for ischemic heart  disease (IHD), 20% for myocardial infarction. Outpatient calls take  the  first place among all out-patient care statistics, and those  associated with IHD are in the leading position among them.  Hospitalization takes the second  place. The absence of LLT caused  the loss of more than 400,000 years of life in economically active age. The direct costs are determined by expenses for hospitalizations in the presence of IHD. The share of direct costs for hospitalizations is 86%, while in the presence of cerebrovascular diseases it is 76.8%. Payments for disability allowance, which refers to direct non-medical costs, exceed 154 million Russian rubles (RUR) for IHD and 104 million RUR for cerebrovascular diseases. The biggest share  of economic burden associated with the lack of LLT in individuals with this risk factor  is accounted for indirect economic losses: about 507 billion RUR in IHD, of which more  than  90  billion RUR are  associated with myocardial infarction. The costs associated with cerebrovascular diseases make up over 305 billion RUR, the vast majority of which is due to stroke: over 248 billion RUR. Due to the low LLT coverage in the Russian Federation, the economic burden associated with its absence is over 80% of the calculated HCS related losses in total.

Conclusion. Economic burden of the lack of LLT in HCS patients is calculated as 530 billion RUR, which is about 0.6% of GDP in 2016, and the largest part of expenditures is related to IHD. The increased awareness of HCS and its improved control with increasing treatment coverage will make possible to lower cholesterol values at the population level, which will also reduce  the economic burden of this risk factor for CVD.

725-732 199
Abstract

Obesity is one of the main risk factors for type 2 diabetes developing. The question of the advantages and disadvantages of using various anthropometric indices [body mass index (BMI), waist circumference (WC), waist-to-height ratio (WHR), lipid accumulation product index (LAPI), visceral obesity index (VOI)] has been under discussion lately.

Aim. To perform an analysis of anthropometric obesity indicators (BMI, WC, WHR, VOI, LAPI) depending on the presence of type 2 diabetes in the adult population of the Russian Federation.

Material and methods. The results of the study "Epidemiology of Cardiovascular diseases and their risk factors in the regions of the Russian Federation" (ESSE-RF) performed in 2012-2014 in 13  regions of the Russian Federation are included into the analysis. People aged  25-64 years (n=20878; 8058 men and 12820 women) were examined. The following indicators in people with/without type 2 diabetes were analyzed: age; sex; anthropometric indicators: height, weight, WC; smoking status  (“never smoked”, “smoked”,  “smokes  now”); alcohol consumption, which was ranked  for “never in the last year” and “a lot” (≥168 g of ethanol per week for men and ≥84 g of ethanol per week for women); the level of systolic (SBP) and diastolic (DBP) blood pressure; heart  rate (HR); levels of glucose, total cholesterol (TC), high density lipoproteins cholesterol (HDL-C), triglycerides (TG); WHR; VOI; LAPI, BMI.

Results. Levels of TC and glucose, excessive alcohol consumption, BMI were selected in a multifactor regression model in men after adjusting for age, region of residence and IVO. The same factors (SBP instead of alcohol and BMI instead of WHR were included in the model) were selected in women. VOI showed the greatest degree of association with type 2 diabetes regardless of gender after adjusting for age and region of residence (in men odds ratio 1,085; p=0.0001; in women odds  ratio 1,136; p=0.0001). Thus, VOI (predictor of type  2 diabetes in population of working age) was common to both sexes.

Conclusion. VOI has statistically significant associations with type 2 diabetes. VOI is the best surrogate marker for measuring the degree of abdominal obesity in the Russian population and can be used to determine the presence of type 2 diabetes in clinical practice. Screening for elevated VOI values in healthy individuals and patients with pre-diabetes can serve as a guide for targeted aggressive preventive interventions.

Participants of the  ESSE-RF Study: Vladivostok: Kulakova N.V., Nevzorova  V.A., Shestakova N.V., Mokshina M.V., Rodionova L.V.; Vladikavkaz: Tolparov G.V.; Vologda: Shabunova A.A., Kalashnikov K.N., Kalachikova O.N.,  Popov  A.V.; Volgograd: Nedogoda S.V., Chumachek E.V., Lediaeva A.A.; Voronezh: Chernyih T.M., Furmenko G.I., Ovsyannikova V.V., Bondarcov L.V.; Ivanovo: Belova O.A., Romanchuk S.V., Nazarova  O.A., Shutemova O.A.; Kemerovo: Barbarash O.L., Artamonova G.V., Indukaeva E.V., Mulerova T.A., Maksimov S.A., Skripchemko A.E., Cherkass  N.V., Tabakaev M.V., Danilchenko Ia.V.; Krasnoyarsk: Grinshtein Yu.I., Petrova M.M., Danilova L.K., Evsiukov A.A., Shabalin V.V., Ruph R.R., Kosinova A.A., Filonenko I.V., Baykova O.A.; Moscow: Gomyranova N.V., Oganov  R.G., Oshepkova E.V.; Orenburg: Libis R.A., Basyrova I.R., Lopina E.A.; Samara: Dupliakov D.V., Gudkova S.A., Cherepanova N.A.; St. Petersburg: Konradi A.O., Baranova E.I.; Tomsk: Trubacheva I.A., Kaveshnikov V.S., Karpov R.S., Serebriakova V.N.; Tyumen: Efanov A. Yu., Medvedeva I.V., Storozhok  M.A., Shalaev S.V.


733-740 147
Abstract

Aim. In the framework of the database of patients with atrial fibrillation established in the Kursk region, to study the clinical and anamnestic indicators, the structure of the combined and concomitant diseases in the patients under study, and also to evaluate the usefulness of the diagnostic methods of the study and drug therapy of this pathology.

Material and methods. The regional study (REKUR-AF) included patients with atrial fibrillation (AF) from 18 years of age and older living in the city of Kursk and seven districts of the Kursk region. Recruitment of patients to the study was conducted from September 2015 to August 2016. When analyzing the outpatient charts of the studied patients, demographic data, the type and duration of AF, cardiovascular diseases (CVD), concomitant noncardiac pathology, laboratory and instrumental examination data, information about hospitalizations for the last year, pharmacotherapy were recorded.

Results. The research included 896 patients with AF. Mean  age  of patients was  69  (62-77) years,  women were  significantly older than  men (p<0.001). When analyzing the most common CVD in patients with AF (chronic heart failure, stable exertional angina, arterial hypertension), it was found  that  comorbid pathology was found  in 99.3% of patients. 22.7% of patients had myocardial infarction (MI) in the past,  12.3% – acute  cerebrovascular accident. From concomitant noncardiac diseases, patients with AF most  often  suffered  from chronic kidney disease, obesity, type 2 diabetes, diseases of the gastrointestinal tract. On the average, one patient had 4 (3-4) diagnoses of CVD, and together with concomitant pathology – 5 (4-6). The medical examination was not in line with required level in the existing diseases. The high risk according to CHA2DS2-VASc scale was revealed in 96.3% of patients and according to HAS-BLED scale – in 52.8%. Patients with AF most often  received antiplatelet agents, angiotensinconverting enzyme  inhibitors, β-blockers, statins and  diuretics. Anticoagulants were  only used  in 18.3% of patients. The average number of prescriptions of drugs  in all patients with AF was  5 (4-6) and  was  significantly (p<0.001) higher in the  group  of patients with MI in the  past (6 [4-6]) compared with the cohort of patients without MI (5 [4-6]).

Conclusion. Patients included into the REKUR-AF study were characterized by a high incidence of combined cardiovascular pathology, a high risk of thromboembolic complications. In most patients, anti-platelet drugs were used as antithrombotic therapy, although they are significantly inferior to anticoagulants in their ability to prevent thromboembolic complications. Anticoagulants were used only in every fifth patient, warfarin was a significant part  (52.6%) among all anticoagulants. Patients with AF also had  an insufficient frequency of laboratory and  instrumental examinations, that  is required according to current  guidelines.

 

PAGES OF RUSSIAN NATIONAL SOCIETY OF EVIDENCE-BASED PHARMACOTHERAPY

741-746 108
Abstract

Aim. Within the framework of the outpatient registry of patients with acute myocardial infarction (AMI), to assess the influence of factors in medical history, especially cardiovascular diseases (CVD) preceding AMI, on the long-term results of the underlying disease.

Material and methods. 160 patients who  sought medical care to the outpatient clinic from March  01,  2014 to June 30,  2015 after  AMI were included into the registry. Patients were observed for at least 1 year (maximum 2.5 years). The primary end point (PEP) of the study were death from any cause,  recurrent cardiovascular complications (non-fatal AMI, cerebral stroke), and urgent hospitalization due to the worsening of the current CVD.

Results. After 1 year of follow-up, 9 (6%) patients died (8 from CVD). A recurrent myocardial infarction occurred in 8 patients, and cerebral stroke in 1 patient. 20 patients were hospitalized due to CVD exacerbation. In total PEP was registered in a fifth part of patients (36 people). Factors that had a negative impact on the endpoint were age (relative risk [RR] 1,05; 95% confidence interval [CI] 1.01-1.09, p=0.016), the presence of cardiovascular diseases or conditions reflecting the severity of the underlying disease before the reference event: ischemic heart disease (RR 2.37; 95%CI 1.05-5.34, p=0.038), previously AMI (RR=5.93; 95%CI 2.28-15.4, p<0.001), percutaneous coronary intervention (RR 9.84; 95%CI 2.02-48.06, p<0.005), disability (RR 4.37; 95%CI 1.82-10.46, p<0.001).

Conclusion. The long-term life and  disease prognosis in patients with AMI remains quite severe.  Adverse long-term outcomes of the  disease are largely determined by anamnestic factors, primarily the  presence of ischemic heart  disease before  the  reference event,  previous AMI. The study indirectly demonstrated that percutaneous coronary intervention in patients with stable ischemic heart disease, at least, does not improve the prognosis of the disease.

POINT OF VIEW

747-756 2146
Abstract

The urgency of the problem of orthostatic hypotension (OH) has increased in recent years. It was due to the high prevalence and its adverse effect on the prognosis and  quality of life of patients, especially the elderly and  oldest old. The purpose of this review was to summarize the contemporary domestic and foreign literature data  about disease. The article presents an updated definition of OH, modern classification, pathophysiology, feature of the  course  of OH in the  elderly, recommendations for diagnosis and  treatment. Particular attention is paid to reviewing the  results of scientific research on the  influence of OH on the  risk of developing coronary  and  cerebrovascular events  and  overall mortality. OH is one  of the  forms  of orthostatic tolerance and diagnostic criteria were determined by the 2011 Consensus as a sustained fall of systolic blood pressure by at least 20 mm Hg and/or a diastolic blood pressure by 10 mm Hg within 3 min of standing. The prevalence of OH ranges depending on the age of the patients and the presence of a number of concomitant diseases: from 6% in healthy people without arterial hypertension up to 50% or more in people older than 75 years with a comorbid pathology. OH is an independent predictor of overall mortality and adverse  cardiovascular events.  OH is associated with an increased risk of serious adverse  cerebrovascular and  coronary  events,  and  may also contribute to cognitive impairment and  the  development of dementia. For today, we have three  clinical options OH: classical, early and delayed OH. In addition, OH is classified based  on etiology – primary and secondary; and pathophysiological principle – neurogenic OH and not a neurogenic OH (or functional). The algorithm for identifying patients with a high risk of development of OH and diagnostic methods are also presented. Non-medicamentous and medicamentous methods of OH treatment are considered.

757-764 195
Abstract

Obesity is one of the leading and the most serious risk factors of cardiovascular diseases. Overweight provokes many metabolic and hemodynamic disorders.  About 30% of inhabitants of the planet have overweight and prevalence of obesity increases by 10% every 10 years according to the WHO data.  The probability of arterial hypertension in obese  patients is 50% higher than in people with normal body mass. Framingham study showed that obesity is an independent, significant risk factor  of ischemic heart  disease, myocardial infarction, cerebral stroke  and  diabetes mellitus. The most dangerous is the central obesity with the preferential fat deposition in the abdomen. Combination of visceral obesity, violation of carbohydrate and lipid metabolism, arterial hypertension, and close pathogenic relationship between these  factors  underlie the isolated symptom complex known  as metabolic syndrome. J. Vague was the first to describe relationship between abdominal obesity with cardiovascular disease and mortality in 1947. In our country G.F. Lang noticed common combination of arterial hypertension with obesity, lipid and carbohydrate metabolism disorders. Thus, metabolic syndrome significantly increases risk and  severity of cardiovascular disease. Within last decades criteria of metabolic syndrome stays constant. The factors  of insulin resistance and  endothelial dysfunction as stages of the pathogenesis of the metabolic syndrome have been  studied in detail. The mechanisms of insulin resistance and endothelial dysfunction are discussed in detail in this article as well as inflammatory markers and the significance of highly sensitive C-reactive protein.

765-773 224
Abstract

The new term «MINOCA» (myocardial infarction with nonobstructive coronary arteries) emerged in the literature about 5 years ago and characterizes the syndrome with heterogeneous etiology and pathogenesis, which reflects the development of myocardial infarction with non-obstructive lesions of the coronary  arteries, occurring in both cardiological and noncardiac diseases. The article gives detail focus on origin, definition, pathological bases of MINOCA. It also examines the role of coronary (non-obstructive atherosclerosis, microvascular dysfunction, coronary  spasm, "myocardial bridge", coronary  arteries dissection) and  non-coronary reasons, caused  by cardiac (cardiomyopathy, myocarditis) and non-cardiac (pulmonary embolism, thrombophilia) diseases.

In analyses of publications much attention is given to the discussion of diagnosis and differential diagnosis, prognosis and treatment of MINOCA. Recommended methods of examination are given depending on the  alleged cause  of the  occurrence of MINOCA. Two clinical cases  demonstrated difficulty in diagnosis of this condition and  the  importance of an individual approach. Attention is also given to the  absence of currently clinical guidelines for the  management of patients with MINOCA and  to the  significant differences in the  use  of different classes of cardiotropic drugs according to different author’s mind.

Author  gives the  opinion that  MINOCA has  a certain practical significance as a preliminary "diagnosis" before  final establishing the  disease. In conclusion, it is emphasized that the MINOCA syndrome terminology and characteristic is controversial now. This mind confirmed by a new definition of this condition in the Forth Universal Definition of Myocardial Infarction (European Society of Cardiology, 2018).

774-784 375
Abstract

The tendency of aging of the population and,  together with it, the increase in the prevalence of arterial hypertension (HT) determines the need  to study  the  peculiarities of treatment of HT in patients of elderly and  senile age.  In this regard, in the  new  Guidelines of the  European Society of Cardiology for diagnosis and treatment of HT (2018), the authors identified groups  of elderly patients (aged 65-79 years) and very elderly patients (aged ≥80 years), blood pressure (BP) levels for the initiation of antihypertensive therapy and target BP levels, and recommended the main principles of antihypertensive therapy. The new  recommendations of the  ESH/ESC in 2018 also presented the  characteristics of HT management in elderly patients. The necessity of mandatory detection of senile asthenia in elderly patients and  determination of the  degree of their independence from outside help is emphasized. In all elderly patients, especially in very elderly or "fragile" patients, it is recommended to evaluate the  presence or development of orthostatic hypotension during treatment, as well as actively to detect episodes of hypotension using the 24-hour BP monitoring. For antihypertensive therapy in elderly patients, the same five classes of antihypertensive drugs and their combination are recommended. It is emphasized that if it is not required for the treatment of concomitant diseases, loop diuretics and alpha-blockers should be avoided because their use is associated with an increased risk of falls. It is recommended to investigate the level of serum creatinine more often to evaluate the kidney function and to detect a possible decrease in the glomerular filtration rate  because of a decrease in BP and  perfusion of the kidneys. The target BP levels indicated in the Guidelines are: systolic BP values 130-139 mm Hg and diastolic BP 70-80 mm Hg. In the Guidelines it is emphasized that elderly patients need careful monitoring of any adverse  side effects of antihypertensive drugs.

CURRENT QUESTIONS OF CLINICAL PHARMACOLOGY

785-789 168
Abstract

This article affects  the problems of using NOAC in the most defenseless groups  of patients with atrial fibrillation: those  who have high bleeding and high thromboembolic risk and elderly. The focus is on comparison of effectiveness and safety of NOACs based  on randomized clinical trials (RCT) and real-world data (RWD). The possible reasons for the different interpretation of the data of the RCT and the RWD are shown. Use of NOAC in reduced doses prescribing according to RCT and RWD are shown. Our own 13-month observation of patients 75 years and older with very high thromboembolic risk (CHA2DS2-VASc – 4,5  points) on rivaroxaban therapy are presented. Good efficacy and  safety  of full and  reduced doses  of rivaroxaban were demonstrated: only 2 episodes of small bleedings and no large bleedings (ISTH criteria) were detected as well as no thromboembolic events.  Thus, even difficult patients with AF and comorbidity may be safely and effectively treated with NOACs taking into consideration integrated approach and correction of modifiable risk factors.

FORUMS

790-794 116
Abstract

The article is devoted to the discussion of the main news  from the annual congress of the European Society of Cardiology (Munich, August 25-29, 2018). The results of just completed randomized clinical trials (RCTs) are reviewed. The RCTs presented at the congress were mainly devoted not to new drugs,  but to the features of the use of already known drugs,  which was important for clinical practice.

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