Rational Pharmacotherapy in Cardiology

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Vol 11, No 5 (2015)
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450-458 1043

Chronic non-infectious diseases are characterized by irregular morbidity and mortality throughout a year.
Aim. To study excess cardiovascular morbidity during winter in Ivanovo Region in 2009-2013 years.
Material and methods. Excess winter morbidity index (EWMI) was calculated using special formula. The incidence of cardiovascular diseases (CVDs) was determined according to the data from the medical information-analytic center of Ivanovo Region. The index was calculated for CVDs in general, for arterial hypertension (HT) and for acute forms of CVDs (acute myocardial infarction and stroke).
Results. The mean EWMI for CVDs for 5 years of the follow-up made up to 77.2% and was higher in women than in men (80% vs 69.5%, respectively). People of working age had lower excess winter morbidity than the population older than working age (53.1% and 88%, respectively).
EWMI for CVDs had significant variability and ranged from 29.0% (2013 year) to 81.1% (2010 year) in men and from 25.2% to 82.9% in women in the same years.
In general, the 5-year mean EWMI for HT was 72.7%; it was higher in men than in women in most of the analyzed years of follow-up.
We had revealed the heterogeneity of the EWMI for HT during the analyzed period in each analyzed group (the minimal values were found in 2011 after the heat wave in 2010). EWMI for myocardial infarction demonstrated excess winter morbidity, men and women had in general similar indices (31.0% and 28.4%, respectively), but it was higher in people of working age as compared with the older ones. This index had a wide range of values. In case of stroke we had revealed no excess winter morbidity; this index was equal throughout a year.
Conclusion. The influence on excess winter morbidity can result in the reduction of cardiovascular morbidity and mortality due to the decreased effect of risk factors; it would also optimize a load on healthcare system, the season irregularity of which must be taken into account when planning a work of medical centers.

459-463 498

Aim. To assess of lipid-lowering therapy with statins in very high cardiovascular risk patients admitted to hospital for coronary angiography and analyze lipid profiles depending on the intensity of lipid-lowering therapy.
Material and methods. A total of 502 patients aged 25-86 years (mean age 61.2±9.4 years) who admitted to the clinic of State Research Center for Preventive Medicine were consecutively included into the study. All of them were examined and underwent coronary angiography. Plasma lipid levels were determined by standard laboratory methods. Results. The levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-cholesterol) and non-high-density lipoprotein cholesterol (HDL-cholesterol) were significantly higher among patients not taking lipid-lowering therapy. 62.1% of patients having a non-intensive lipid-lowering therapy and 52.5% of the patients having intensive therapy reached the target level of TC for high-risk patients. However, only one third of patients reached the target TC level for patients at very high risk in these patient groups. Target level of LDL-cholesterol <1.8 mmol/l among all patients was reached only in 11.2% of patients treated with low doses and in 12.7% of patients treated with high doses of lipidlowering drugs. 
Conclusion. Dyslipidemia management in real clinical practice remains suboptimal, with a substantial proportion of patients fails to achieve guideline-recommended target lipid levels to reduce the risk of cardiovascular diseases and their complications.

464-469 475

Aim. To evaluate the efficacy of atorvastatin therapy in prevention of atrial fibrillation (AF) development after coronary artery bypass graft (CABG) surgery in patients with ischemic heart disease (IHD) with the assessment of inflammation, sheer stress and myocardial injury indicators.
Material and methods. The study included 105 patients with IHD who were divided into two groups: patients of group 1 were treated with atorvastatin (59 patients, 81% males, mean age 62.1±7.5 years); patients of group 2 received no HMG-CoA reductase inhibitors (46 patients, 89% males, and mean age 61.7±8.1 years). 

Results. Postoperative AF occurred more often in patients of group 2 (41.3% vs 16.9%; р=0.047). Laboratory analysis revealed the following: the levels of total leukocytes, interleukin-8, interleukin-10, C-reactive protein, fibrinogen, superoxide dismutase and troponin did not different significantly among the patients of two groups. Interleukin-6 level in preand postoperative period was significantly higher in patients of group 2 (35.4±28.5 pg/ml vs 24.1±14.8 pg/ml, р=0.03; 63.7±54.8 pg/ml vs 50.7±40.8 pg/ml, р=0.04, respectively). 

Conclusion. Our study has shown that atorvastatin therapy contributed to the reduction of number of new cases of AF after CABG in patients with IHD. At that, the efficacy of atorvastatin therapy correlated with the size of left atrium and the severity of inflammatory response. Patients with atorvastatin therapy had significantly lower interleukin-6 level, as a proinflammatory marker, in preand postoperational period as compared with the patients without such treatment.

470-476 458

Aim. To study the predictors of atherosclerotic lesions of arteries identified through a multi-channel volume sphygmography (MCVS).
Material and methods. Simultaneous survey of 441 rural residents over 40 years old was performed. Synchronous registration of blood pressure (BP) on four limbs using MCVS was fulfilled, and differences in systolic BP between arms (ΔSBParm) and legs (ΔSBPleg) were calculated. Ankle-brachial index (ABI) was also evaluated. ΔSBParm≥15 mm Hg or ΔSBPleg≥15 mm Hg or ABI≤0.9 were considered as the markers of atherosclerotic arterial disease.
Results. A significant asymmetry of SBP (≥15 mmHg) was found in 7.7% [95% confidence interval (CI) 5.5-10.6%] of patients in the upper limbs and in 6.8% (95 % CI 4.89.6%) of patients in the lower extremities. The relative risk of asymmetry of SBP (≥15 mm Hg) in the upper limbs increased in hypertension and obesity, and in the lower limbs in men and diabetes. Various quantitative risk factors of the onset and progression of atherosclerosis (age, body mass index, waist circumference, blood glucose, BP level) had a positive correlation with the level of asymmetry of SBP on the limbs. Using MCVS and the appropriate combinations of features (SBP asymmetry or ABI≤0.9) allowed us at the stage of screening to find out blood flow disturbances in the arteries of the extremities in 14.7% (95% CI 11.7-18.4%) of patients. This detection frequency was significantly higher than that when using only ABI.
Conclusion. Identification of significant SBP asymmetry (≥15 mm Hg) in the limbs may improve the diagnosis of atherosclerotic arterial disease at the stage of screening.

477-482 439

Aim. To study the clinical course of acute myocardial infarction (MI) with ST segment elevation (STEMI) and the features of inpatient treatment in patients with and without diabetes mellitus (DM).
Material and methods. STEMI patients (n=83), who were hospitalized in 2014, were included into the study. The patients were divided into two groups according to the presence or absence of glucose metabolism disorders: Group 1 (patients with type 2 DM; n=38) and Group 2 (patients without glucose metabolism disorders; n=45). Baseline demographic, clinical, laboratory and instrumental characteristics of the patients, along with the features of hospital treatment, were studied. 

Results. In group 1 compared with group 2 hypertension was detected significantly more frequently (73.7% vs 49%; p<0.05), and a class of acute heart failure (Killip) at admission was higher (1.46±0.6 vs 1.23±0.57; p<0.05). STEMI was complicated by an acute left ventricular aneurysm 12% more often in patients of group 1 (p<0.05). The duration of inpatient treatment was also higher in patients of group 1 (18±4.1 vs 16±3.6 days; p<0.05).
Conclusion. Only 21% of the patients with DM and STEMI had adequate treatment of ischemic heart disease and a quarter of the patients in this group had no adequate DM therapy before the admission. Patients with DM had a higher incidence of in-hospital STEMI complications and a higher duration of inpatient treatment. 

483-488 2412

Aim. To study the efficacy of use of amiodarone with ivabradine combination or amiodarone with bisoprolol combination in the prevention of atrial fibrillation (AF) recurrence in patients (pts) with left ventricular diastolic dysfunction (LVDD) after conversion to sinus rhythm.
Material and methods. 65 patients (40 males, 25 females) aged 53±8 years with persistent AF and LVDD were included into the study and randomized into 3 groups to receive ivabradine and amiodarone (22 pts), bisoprolol and amiodarone (22 pts) or amiodarone alone (21 pts). Left atrium (LA) volume indices, LA longitudinal strain rate (LASR) in systole, LV mass index, mean heart rate (HR), 24-hour HR variability and the incidence of AF by 96 h ECG monitoring were measured after the titration period, and after 3 and 6 months of follow-up. 

Results. After 6 months of follow-up group 1 revealed significantly lower maximum LA volume index (21.3±2.4 vs 25.2±3.0 and 28.7±3.6 ml/m2 in the 2nd and control groups, respectively), P-wave LA volume index (15.3±3.5 versus 18.1±3.8 and 20.4±4.0 ml/m2 in the 2nd and control groups, respectively), and LA systolic volume index (7.3±1.2 versus 9.4±1.6 and 9.6±1.7 ml/m2 in 2nd and control groups, respectively). The incidence of side effects in group 1 was significantly less than that in group 2 and was not different compared with control group. 

Conclusion. Ivabradine and amiodarone combination provides better prevention of AF recurrence and less side-effects in pts with LVDD and persistent AF after sinus rhythm restoration as compared with bisoprolol and amiodarone combination, it also reduces LA maximum, conduit and systolic volumes, and increases LASR.

489-495 500

Aim. To establish the role of insulin-like growth factor-1 (IGF-1) in left ventricular remodeling in female patients with arterial hypertension (HT) and metabolic syndrome (MS) with different stages of obesity.
Material and methods. The study included 108 women with HT and MS, who were divided into 3 groups according to the stage of obesity, and 28 healthy women. The level of IGF-1, hemodynamic status and types of left ventricular remodeling were assessed. 

Results. Concentric remodeling and IGF-1 elevation (165.3±12.03 ng/ml) prevailed in patients with HT and first stage of obesity. Concentric hypertrophy of left ventricle and normal level of IGF-1 (118.5±10.05 ng/ml) were established in patients with second stage of obesity. Lack of IGF-1 (96.4±8.11 ng / ml) was determined in women with third stage of obesity and eccentric hypertrophy. Correlation analysis in patients with 2-3 stages of obesity showed significant associations between the level of IGF-1 and hemodynamic parameters. 

Conclusion. Changes in the level of IGF-1 in patients with AH and MS correlate with types of remodeling and stage of obesity. 


496-503 538

Aim. To assess the cost-effectiveness of apixaban in the treatment and secondary prevention of venous thromboembolism (VTE) compared with low molecular weight heparin (LMWH)/warfarin and other new oral anticoagulants (NOACs).
Material and methods. Cost-effectiveness analysis was performed using a Markov model, developed on the basis of the results of AMPLIFY AMPLIFY-Ext trials, and network meta-analyzes on the use of antithrombotic drugs in acute VTE and long-term administration after VTE. Markov cycle duration was 3 months. The duration of therapy in the simulation was 6 and 12 months. The time horizon of the study was 5 years. Life expectancy and costs were discounted by 3.5% per year. The costs on drugs were estimated based on the registered marginal cost price. Besides, the analysis was performed to the weighted average auctions prices for NOACs. The costs of monitoring and treatment of complications were calculated on the basis of the collective agreement of compulsory health insurance system (St. Petersburg, 2015). 

Results. Apixaban provided significant cost savings compared with other modes of anticoagulant therapy for hospital treatment. Apixaban provided cost savings compared with other NOACs with a minimal increase in life expectancy with regard to quality in long-term analysis. Apixaban provided an increase in life expectancy compared with the appointment of LMWH/warfarin, but required some increase in costs. At therapy duration of 6 months, the costs per one additional year of life with regard to quality and to one additional calendar year of life were 309.8-403.7 and 481.6-627.4 thousand rubles, respectively; at therapy duration of 12 months – 1254.4-1476.9 and 649.0-764.1 thousand rubles, respectively. 

Conclusion. Apixaban provided a reduction in the incidence of bleeding compared with other NOACs and LMWH/warfarin with comparable efficacy in treatment and secondary prevention of VTE. Apixaban therapy costs were lower than these for other NOACs, and the additional cost of apixaban therapy compared with LMWH/warfarin proved to be highly cost effective in the treatment of 6 months duration and economically acceptable in therapy during 12 months.

504-509 468

Aim. To study the lipid-lowering therapy, the adequacy of its control, as well as the awareness of patients at a high cardiovascular risk of atherosclerosis problems and the dynamics of these parameters in 3 years.
Material and methods. Patients with dyslipidemia (113 patients in 2011 and 100 patients in 2014) who were treated in the cardiology clinic were examined. Patient survey on the lipid-lowering therapy and its monitoring was conducted. Medical records of patients were studied also. 

Results. The number of patients informed on atherosclerosis aspects increased from 52% to 59% (p>0.05) in 3 years. Laboratory control of lipid metabolism remained inadequate. Insufficient lifestyle modification changes (diet, smoking, physical inactivity) were present. Lipid-lowering drugs were regularly taken by 26% of the patients in 2011 and 29% in 2014 (p>0.05) and a control of lipid metabolism was absent in 12% and 14% of the patients, respectively (p>0.05). Only 27% of the patients gave the importance of lipid-lowering therapy 10 points on a 10-point scale. 

Conclusion. Dynamics of patients awareness on atherosclerosis and measures taken to correct and control lipid metabolism disorders were insignificant within 3 years. High costs of medication and the underestimation of treatment importance by the patient play an important role in poor adherence.


510-516 531

Background. According to the some studies tocilizumab therapy (TCZ) in patients with rheumatoid arthritis (RA) is accompanied by deterioration of blood lipid profile.
Aim. To study changes in serum lipid parameters in patients with RA treated with a combination of tocilizumab and methotrexate compared with methotrexate alone for 24 weeks of observation.
Material and methods. Patients (n=72) with RA were included into the pilot non-randomized 24-week study and divided in two groups: 1) TCZ+MTX group (n=39; women 30; median age 51 [43-55] years; 6 i.v. infusions of TCZ 8 mg/kg + МТX 10-20 mg/week); 2) MTX group (n=33; women 23; mеdian age 56 [48-63] years; MTX 7.5-20 mg/week).
Results. At the baseline, similar proatherogenic blood profile was observed in both groups. The patients of MTX group more frequently took statins (n=19; 57.6%) compared with the group TCZ+MTX (n=7; 18%), (p<0.05). The lipid levels correlated positively with traditional risk factors (p<0.05). RA activity and duration correlated negatively with high density lipoprotein cholesterol (HDL-C), (p<0.05). Good/satisfactory anti-inflammatory effect was achieved in both groups after 24 weeks of treatment. Patients of TCZ+MTX group showed an increase in total cholesterol and HDL-C levels by 11% and 110%, respectively and decrease in plasma atherogenic index (PAI) by 47%, (p<0.05). HDL-C level increased by 22% and PAI decreased by 16% in patients of MTX group (p<0.05). Among patients of MTX group without statin therapy HDL-C as well as non-HDL-C levels were increased by 24% and 27%, respectively (p<0.05); PAI did not change significantly in this subgroup. Among patients of MTX group treated with statins isolated increase in HDL-C level by 22% and decrease in PAI by 37.3% (p<0.05) were observed. A number of patients with achieved target levels of all studied lipid parameters did not change significantly in both groups.
Conclusions. TCZ+MTX combined therapy as well as MTX monotherapy are associated with similar improvement in lipid parameters. Adjusted statin doses may be needed to achieve target serum lipid profile in RA patients.


517-521 440

News of the European Society of Cardiology Congress (London, 2015) is presented. The results of recent randomized controlled trials and observational studies (registers) data are discussed.


522-528 727

Currently, cardiovascular diseases (CVD) remain the main problem in the world and in Russia in particular. The study of the causes and progression of atherosclerosis is a critical moment in the fight against CVD. Adipose tissue and processes that occur in it attracts attention in recent years. The important role of adipose tissue as an endocrine and immune organ is revealed as well as its participation in the development of the inflammatory process. This leads to the development of initial manifestations of atherosclerosis a precursor of many metabolic disorders and CVD. Particular attention causes adipokines regulatory peptide hormones in the adipose tissue, as well as insulin, due to its close relationship with the adipose tissue and especially with adiponectin and leptin. Recent data on the role of adiponectin, leptin and insulin in the pathogenesis of atherosclerosis in order to identify new potential targets among peptide hormones for the treatment of atherosclerosis are presented. 

529-534 1178

The rate of cardiac events (myocardial infarction, death) in non-cardiac surgery is about 2% to 3%. However, increase in troponin is noted much more often from 5% to 25% of patients. Such an isolated increase in troponin in the absence of criteria for myocardial infarction is also called "myocardial injury after non-cardiac surgery". This condition is associated with poor prognosis directly after surgery and in the long term. Current data on screening troponin level after surgery and proposals for the treatment of patients with elevated levels are presented. Different points of view on the issue are discussed. This allows more fully illuminating the problem and helping the clinician in treatment of these patients.


535-542 600

Features and possibility of application of the calcium channel blocker lercanidipine in cardiology practice are discussed. The use of lercanidipine in patients with hypertension is supported by extensive evidences. The use of lercanidipine in certain categories of patients, including patients receiving combination therapy is also considered. The safety of lercanidipine in cardiac patients is discussed separately.

543-547 669

Currently there are no generally accepted guidelines for the use of apixaban together with CYP3A4 and/or P-glycoprotein (P-gp) inhibitors. Analysis of clinical and pharmacological studies suggests that apixaban dose should be reduced to 2.5 mg twice daily when co-administered with a strong CYP3A4 and P-gp inhibitors, such as azole antimycotics, HIV protease inhibitors and clarithromycin. However, it is preferred to avoid apixaban combination with strong CYP3A4 and P-gp inhibitors in patients with a creatinine clearance (CrCl) <30 mL/min. According to preliminary calculations, apixaban dose should also be adjusted in patients with CrCl <70-80 ml/min, receiving less potent inhibitors of CYP3A4 and/or P-gp, such as diltiazem, naproxen, verapamil, amiodarone and quinidine. 


548-550 400

Pavel E. Lukomsky

551-552 271

New data of the real clinical practice confirms low incidence of major bleeding when using rivaroxaban in patients with non-valvular atrial fibrillation 

553-554 243

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