Rational Pharmacotherapy in Cardiology

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Vol 10, No 3 (2014)
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264-274 1022

Early diagnostics of insulin resistance (IR) is one of the methods of primary prevention of cardio-vascular diseases and type 2 diabetes mellitus. The HOMA-IR index and ratio of plasma triglyceride to high-density lipoprotein cholesterol concentration are the most frequently used indices in clinical and epidemiological scientific research. Prognostic value and efficacy of these tests as a screening method are not high. What method of IR detection should be used in clinical practice and how to interpret received values of the indices is still a matter of dispute.

Aim. To evaluate informative value, sensitivity and specificity of a new metabolic index (MI) for IR estimation in comparison with the calculated HOMA-IR index.

Material and methods. A total of 845 patients (298 men, 547 women) were enrolled into the further study after an outpatient regular medical check-up of 2,615 persons. Mean age of the patients was 45.77±12.18 years, body mass index – 28.95±1.44 kg/m2. To evaluate lipid and carbohydrate metabolism blood chemistry parameters were assessed. IR was determined by the Homeostasis Model Assessment (HOMA-IR) and an oblique calculated index based on lipid metabolism parameters. In accordance with the developed screening method of IR detection (invention patent № 2493566) MI considering carbohydrate and lipid changes was proposed.

Results. Calculation of MI and its threshold level was performed by analysis of a characteristic curve. Graphical dependence between sensitivity and specificity of the proposed index was demonstrated: sensitivity of the test was 75.7%, specificity – 89.1%. Probability of IR at MI value >7.0 was 63.5% (positive predictive value), probability of IR absence at the index value ≤7.0 was 93.6% (negative predictive value). The general accuracy of the test, which is characterized by the area under the characteristic curve, was 0.881 with 95%-confidence interval within 0.854-0.905.

Conclusion. The importance of negative result – absence of IR at normal values of MI and use of routine blood chemistry parameters for its calculation allows to recommend MI for IR screening in clinical practice. Distinction of the proposed method of IR diagnostics from the other known oblique laboratory methods is in easy calculation based on the routine biochemistry parameters detected in venous blood on one occasion. Use of the proposed MI allows to economically and efficiently estimate indirectly sensitivity to insulin without additional assessment of laboratory indices.

275-282 886

Background. For prevention of thromboembolic events in patients with non-valvular atrial fibrillation (NVAF) the following types of antithrombotic therapy are used: anticoagulant therapy with vitamin K antagonists (such as warfarin), antiplatelet therapy (such as acetylsalicylic acid) and novel oral anticoagulants such as apixaban, rivaroxaban and dabigatran. Administration of vitamin K antagonists (VKA) is complicated by the need for individual dose adjustment and frequent monitoring of international normalized ratio (INR). Both warfarin and acetylsalicylic acid are widely used for thrombosis prevention in patients with NVAF in the Russian Federation.

Aim. To evaluate the cost-effectiveness ratio of apixaban compared with warfarin and acetylsalicylic acid in patients with NVAF from the Russian Federation national health care system perspective.

Material and methods. This analysis used a Markov model that allowed estimation of the incremental cost-effectiveness ratio (ICER) for apixaban as compared with warfarin and acetylsalicylic acid over lifetime horizon in VKA suitable and VKA unsuitable patients with NVAF respectively. The model enclosed cardiovascular event rates based on the results of the randomized clinical trials comparing clinical effectiveness and safety of apixaban with warfarin (ARISTOTLE) and acetylsalicylic acid (AVERROES). The following cardiovascular events were taken into consideration: ischemic and hemorrhagic stroke, systemic embolism, intracranial hemorrhage, other major bleeds, clinically relevant non-major bleeds and myocardial infarction. Direct medical costs were determined based on the rates of the compulsory national medical insurance system. The price of the antithrombotic drugs was taken as a weighted average tender price for the year 2013. In the model both costs and benefits (quality-adjusted life years and life-years) were discounted at 3.5%. Cost-effectiveness threshold was set at 1.4 million rubles per quality-adjusted life year (QALY) gained and corresponded to the three times GDP per capita in 2013 in the Russian Federation. Sensitivity analysis explored the impact of the treatment discontinuation rates, patients’ age and quality of INR monitoring on the cost-effectiveness of apixaban.

Results. In the base case analysis it was demonstrated that apixaban as compared with warfarin and acetylsalicylic acid provided additional 0.187 and 0.255 life years as well as additional 0.187 and 0.214 QALYs respectively. Over lifetime horizon apixaban as compared with warfarin and aspirin required additional treatment costs equal to 112.72 and 101.35 thousands rubles, respectively. With that estimated incremental cost-effectiveness ratio for apixaban as compared with warfarin and acetylsalicylic acid was 603.92 and 473.02 thousands rubles per QALY respectively. The results were robust in sensitivity analysis.

Conclusions. Apixaban is expected to be a cost-effective alternative to warfarin and acetylsalicylic acid in patients with NVAF from the Russian Federation national health care system perspective. Apixaban may be recommended for inclusion into formulary reimbursement lists as an alternative to warfarin.

283-287 559

Aim. To assess the effect of the 24-week antihypertensive therapy with fixed-dose drug combination (lisinopril plus amlodipine) on endothelial dysfunction and renal function in patients with arterial hypertension (HT) and diabetes mellitus (DM) type 2.

Material and methods. 30 hypertensive patients with DM type 2 (aged 40-65 years) were included into the study. Endothelial function (plasma and vascular components) and renal function were studied.

Results. Combined antihypertensive therapy significantly improved parameters of endothelial function in patients with HT and DM type 2: production of nitric oxide (NO) in blood serum and urine increased by 122.8% and 65.8%, respectively. Along with these secretion of endothelin (ET-1) in serum and urine decreased by 26.1% and by 76.1%, respectively, p<0.05. A statistically significant redistribution of patients by type of microcirculation was established: the share of patients with normal type of microcirculation increased by 73.4%. There was a statistically significant reduction of proteinuria and albuminuria by 58% and 43.6%, respectively. The share of patients with chronic kidney disease with an estimated GFR 30-60 ml/min/1.73 m2 decreased by 16.7%.

Conclusions. It has been shown that the prescription of a long-term antihypertensive therapy with dose-fixed combination (lisinopril plus amlodipine) is safe and effective for endothelial function improvement, including renal endothelium, with no negative effect on glucose and lipid metabolism in patients with HT and DM type 2.


288-292 588

Aim. To evaluate the frequency of the prescription of cardiovascular drugs in patients before the reference acute myocardial infarction (AMI) based on the register "LIS-1" (Lubertsy mortality study of patients after myocardial infarction).

Material and methods. Stage 1: development of the Register of patients with AMI admitted to cardiology departments of hospitals in Luberets district, Moscow region (2005-2007) and discharged for outpatient treatment. Median follow-up – 1.6 years (1.0, 2.4). The primary endpoint – total mortality. Stage 2: the continuation of register "LIS-1" (2011-2012).

Results.1133 patients (mean age of men 60.1±0.5, women – 71.4±0.4 years) were included in the 1st stage of the study; 172 (15.2%) died in the hospital. Before the reference hospitalization 21.4% of patients had been receiving b-blockers, 35.3% - renin-angiotensin-aldosterone system (RAAS) inhibitors, 15.7% - antiplatelet agents, 1.9% - statins, 13% of patients - diuretics. Statistically significant (adjusted for sex and age) positive impact on hospital mortality reduction had a treatment with b-blockers [OR=0.542, CI=0.357-0.824, p=0.004] and RAAS inhibitors [OR=0.710; CI=0.512-0.986, p=0.040] prior to the development of acute myocardial infarction. As the number of patients receiving statins and antiplatelet agents was small, the contribution these drugs intake on hospital mortality was not identified. 272 patients (mean age 63.6±12.6 years) were included on the second phase of the study. The information about the received therapy before reference hospitalization was reported by 173 patients: 39% of patients used b-blockers, 47% - RAAS inhibitors, 37% - antiplatelet agents, 15% - statins, 15% of patients - diuretics. Positive changes in the frequency of the prescription of essential drugs were observed in 5 years: a significant increase in number of patients with b-blockers (p<0.001), RAAS inhibitors (p<0.01), antiplatelet agents (p<0.05) and statins (p<0.001). The number of patients with diuretics did not significantly change.

Conclusion. The Register "LIS-1" (Lubertsy study of mortality in patients after myocardial infarction) allowed not only to assess data on clinical practice at a certain period, but also to evaluate the changes in drug therapy of patients with high and very high cardiovascular risk.


293-298 589

Aim. To study the intensity of the intravascular microcoagulation in patients with atherothrombosis (AT), chronic obstructive pulmonary disease (COPD) and thrombophilia.

Material and methods. 115 patients were enrolled into the study: 37 patients with COPD (22 with thrombophilia and 15 without thrombophilia); 37 patients with AT (23 with thrombophilia and 14 without thrombophilia); 41 patients with COPD+AT (24 with thrombophilia and 17 without thrombophilia). In the control group 53 healthy people (39 with thrombophilia and 14 without thrombophilia) were included. Median age was 62 (56.5, 69) years. The intensity of intravascular microcoagulation was measured: platelet factor 4 (PF4) by ELISA, D-dimer by ELISA, XIIa-dependent fibrinolysis (time). Polymerase chain reaction was used for detection of such trombophilia parameters as Leiden mutation, prothrombin gene mutation 20210A, mutation in the gene of methylenetetrahydrofolate reductase (MTHFR) and plasminogen activator inhibitor-1 (PAI-1).

Results. The level of PF4 and D-dimer was significantly higher while fibrinolytic activity was lower in COPD (103.5 ME/ml, 70 ng/ml, 650 s, respectively), AT (127.1 ME/ml, 96,9 ng/ml, 850 s, respectively) and COPD+AT (136.5 ME/ml, 106.5 ng/ml, 1148 s, respectively) groups as compared with the control group (p<0.05). When analyzing the level of intravascular coagulation parameters in patients with thrombophilia and without it, levels of PF4, D-dimer and XIIa-dependent fibrinolysis (time) were significantly higher in thrombophilia subgroups among all patients (p<0.05). In patients with thrombophilia levels of these parameters were significantly higher in those with two or more thrombophilia gene polymorphisms than with one (p<0.01).

Conclusion. The intensity of intravascular microcoagulation increases in patients with thrombophilia, atherothrombosis and COPD.

299-302 595

Aim. To study the effect of antiviral therapy on some hemodynamic parameters of the heart and the liver in patients with viral cirrhosis.

Material and methods. In 75 patients with chronic viral cirrhosis evaluation of segmental systolic and diastolic function using pulsed tissue Doppler mapping and global diastolic function by the method of Doppler echocardiography was performed. Blood flow in the veins of the liver was determined by means of ultrasonic Dopplerography. 16 patients had previously received antiviral therapy - interferon combined with ribavirin - with the formation of a sustained virologic response (1st group), the remaining 59 (2nd group) had never received antiviral therapy. The control group consisted of 19 healthy individuals.

Results. In patients with chronic viral cirrhosis the increase of the left atrium, diastolic and systolic dimensions, sphericity index and left ventricle mass (p<0.001) were revealed. The right ventricle increased in size with the impairment of its diastolic function and the reduction in longitudinal systolic velocity while pulmonary artery and its branches expanded with the increase of flow velocity in it (p<0.001). Dilation of the splenic vein in the 1st (30%) and 2nd groups (46%) was detected as compared with the control group (p<0.001). Standard deviation normal to normal (SDNN) of RR interval durations reflecting general autonomic tone increased in the 1st and 2nd groups and it was 42% and 62% lower, respectively, in comparison with this index in the control group (p<0.001). These disorders prevailed in patients who were not receiving antiviral therapy, moreover, they showed acceleration of blood flow in the hepatic vein and reduction in longitudinal systolic velocity at the fibrous ring of the mitral valve (p<0.001). The correlation between systolic velocity on the fibrous ring of the mitral valve, high viral load and a diameter of splenic vein was revealed.

Conclusion. Evidence suggests that patients not treated with antiviral therapy have worse prognosis and hemodynamics of the heart and liver than patients who receive specific treatment.


303-306 608

Adequate primary and secondary prevention of thromboembolic complications is one of the main goals of management of patients with atrial fibrillation. Many years of practice and experience of warfarin use, unfortunately, did not lead to wider and more efficient use of anticoagulation therapy. New oral anticoagulants devoid of drawbacks of warfarin, which prevented its prescription and long-term use, have appeared in the past few years. One of them, the most studied, with the largest list of indications for use, and very attractive, is rivaroxaban.


307-311 853

Some aspects of prevention of thromboembolic events in patients with atrial fibrillation, in particular, the use of implantable left atrial appendage occluding devices are discussed. Along with the literature review on this issue, the results of authors own experience of left atrial appendage occluding devices implantation is presented.


312-316 645

The problem of vascular aging is discussed. Special attention among the signs of vascular aging is paid to the activation of the renin-angiotensin-aldosterone system as a source of chronic inflammation and oxidative stress, as well as to its relation to replicative cellular senescence. Potential routes of exposure to these processes are also considered.

317-321 1116

For the long time the systolic myocardial dysfunction was traditionally associated with the severity of chronic heart failure (CHF). Increasing number of patients with symptoms of CHF but without systolic dysfunction has drawn the attention of specialists to so-called CHF with preserved ejection fraction. Prognosis in CHF with preserved ejection fraction may be as bad as in CHF with reduced ejection fraction. Significant changes in views on the pathogenesis of CHF led to the creation of new therapeutic approaches in the treatment of this disease. However, at present, convincing evidence base of mortality reduction in patients with CHF with preserved ejection fraction using well-known therapeutic agents is unavailable. It makes conduct active searches for new biological markers of diastolic heart function. Participation of proinflammatory cytokines, in particular GDF-15, in the process of elasticity reduction and relaxation disorders of left ventricular myocardium, may be of great importance in the development of new medical agents designed to delay the progression of CHF with preserved ejection fraction.

322-327 540

The use of modern accelerated diagnostic protocols in patients with suspected acute coronary syndrome is discussed. Evidence base that can give occasion to selection of acceptable accelerated diagnostic protocol for safe exclusion of acute myocardial infarction early after seeking medical attention is presented. Advantages and disadvantages of certain protocols are discussed.

328-333 1101

Characteristics of atrial fibrillation pathogenesis in patients with chronic obstructive pulmonary disease are discussed. The impact of chronic obstructive pulmonary disease treatment on the onset and course of atrial fibrillation, as well as approaches to the treatment of atrial fibrillation in this category of patients are also considered.


334-338 544

Various aspects of the safety of statins in clinical practice are discussed: hepatotoxicity, myopathy and rhabdomyolysis, the impact on the diabetes and cognitive dysfunction onset, renal function impairment.

339-345 758

Comorbidity of cardiovascular diseases reciprocally aggravates their course and induces the need to use safety and well-tolerated drugs. Pharmacological and pharmacokinetic properties of lercanidipine – the third-generation calcium channel blocker – are characterized by high lipophilicity and tissue selectivity. Clinical studies provide evidence of antihypertensive efficacy and safety of lercanidipine that is successfully used in patients with arterial hypertension and coronary heart disease.

346-350 489

As many languages you know, so many individuals you are (interview with V. Moiseev).


351-352 416

Academician E.I. Chazov is 85!

353-355 371

TCT Russia — XVI Moscow international course on roentgen-endovascular diagnostics and therapy has finished its work.

359 381

Galen Prize in Russia.

360 383

European Medicines Agency approved apixaban use in cardioversion.

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ISSN 1819-6446 (Print)
ISSN 2225-3653 (Online)