Rational Pharmacotherapy in Cardiology

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Vol 9, No 6 (2013)
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611-618 637

At the present time ischemic heart disease (IHD) continues to be the leading cause of cardiovascular mortality. Improvement of treatment methods is an important aspect in reduction of IHD fatal complications.
Aim. To carry out a meta-analysis of several clinical and epidemiological studies with research on the use of drugs with established prognostic effect in patients with IHD.
Material and methods. Analysis of dynamics in drug prescription in IHD was conducted based on Russian clinical and epidemiological trials, performed from 2004 to 2009 years.
Results. The total amount of patients was 17345. Majority of them suffered from arterial hypertension (81.6%), one third had a history of myocardial infarction, more than a half revealed heart failure (59.8%). At that history of diabetes mellitus was only registered in 10.5% of the patients varying from 8% to 17.6%. Lipid metabolism disorders were present in more than a half of the patients. On the average one in four patients was obese.
At drug therapy analysis it was found out that 6.4% of the IHD patients received no medications. Statins intake increased from 5.3% to 85.7% in men and from 9.6% to 69.3% in women in last 5 years. Incidence of the renin-angiotensin-aldosterone system blockers intake increased by 13% in the both genders. Men with IHD received antiplatelet agents more often than women. So, only 45.9% of women received these drugs in 2004 and 57.9% in 2009, while men increased antiplatelet agents use from 58.5% in 2004 to 63.5% in 2009. Men received beta-block- ers by 14% more often in 2009 (74.6%) than in 2004 and women – by 30% (82.4%).
Conclusion. The incidence of the prescription of the drugs with established prognostic value has increased recently. At that rate of IHD mortality in cardiovascular mortality structure continues to be high probably due to inadequate treatment. First, the number of coronary surgical interventions in our patients is significantly lower than in the other countries. Second, despite con- siderable increase in the drug use, doses and adherence to treatment remain insufficient. Representative trials with participation of different-level healthcare institutions are reasonable.

619-626 636

Concept of deterioration of myocardial contractile function under long-term intake of antiarrhythmic drugs may be regarded as one of the myths of modern cardiology. Multiple references to negative influence of majority of antiarrhythmic drugs on myocardial inotropic function are speculative. Studies on estimation of influence of arrhythmia treatment strategy on myocardial contractile function are almost absent.
Aim. To estimate dynamics of myocardial contractile function in patients with ischemic heart disease (IHD) and persistent atrial fibrillation (AF) compared among those treated with amiodarone 200 mg daily and with bisoprolol 5 mg daily.
Material and methods. A total of 47 IHD patients with persistent AF were enrolled into the study. Sinus rhythm (SR) was restored during the first 24 hours of hospitalization in all the pa- tients. After SR restoration the patients were randomly allocated to two groups receiving either amiodarone 200 mg daily during 6 months for SR maintenance (group 1) or bisoprolol 5 mg daily for ventricular rate (VR) control (group 2). To estimate myocardial inotropic function all patients underwent steady-state radionuclide ventriculography (RVG) and echocardiography during the first 24 hours after SR restoration and 6 months later.
Results. We revealed changes in left ventricle (LV) diastolic function, reduction of left atrium (LA) contribution to LV diastole and enlargement of LA anterior-posterior dimension during the first 24 hours after SR restoration in the patients of both groups.
6-month SR maintenance in the first group of patients promoted significant decrease in isovolumic relaxation time (IVRT) from 103.4±1.01 ms to 96.4±1.1ms (р=0.02) and reduction of LA anterior-posterior dimension up to 36.1±3.8 mm (р=0.03). Target VR achievement in the second group of patients promoted restoration of LV diastolic function (decrease in IVRT from
104.3±1.2 ms to 97.3±1.2 ms; р=0.03) but did not influence LA size (44.1±3.1 mm and 43.5±3.0 mm, respectively). Atrial inotropic function was only changed in the patients of group 1, the patients of group 2 did not reveal significant change in LA contribution to LV diastole.
Conclusion. 6-month SR maintenance at amiodarone intake in IHD patients with persistent AF resulted in LA contraction, restoration of its contractility and improvement of LV diastolic parameters. Target VR for 6 months of bisoprolol intake led to LV diastolic function improvement, but did not influence LA dimension and contractile function.

627-632 535

Aim. To study seasonal changes in cardiovascular mortality in winter in Arkhangelsk, Ivanovo and Saratov regions – Russian regions with different climatic and geographical characteristics.
Material and methods. Comparison of mortality in Arkhangelsk, Ivanovo and Saratov regions in 2007-2012 in January-March, December and April-November was performed by multivariate analysis of variance. Significance of differences was assessed by t-test of analysis of variance using programme GLM of SAS system.
Results. Significantly higher cardiovascular mortality in population of Arkhangelsk (by 12.0%), Ivanovo (by 13.4%) and Saratov (by 11.5%) regions, as well as higher overall death-rate, during January-March, December, compared with April-November (p<0.0001) were found. Cardiovascular mortality decreased from 2007 to 2012 by 32.4% and by 32.9% per year and per January-March, December, respectively (p<0.0001). Higher cardiovascular mortality in the cold months of the year persisted in 2007-2012 and was higher than mortality per whole year by 8-14%. This difference in mortality did not decrease significantly (p>0.05).
Conclusion. These findings point out the necessity of elaboration and implementation of the measures to prevent a winter increase in mortality, including the prevention of negative impact on the population of lowtemperature air, seasonal prophylaxis of acute respiratory viral infection, influenza and its complications, pharmacologic and non-pharmacologic prevention of cardio-vascular complications.

633-639 860
Aim. To study the clinical and hemodynamic efficacy of monotherapy with ACE inhibitor perindopril or beta-blocker carvedilol in patients with chronic heart failure (CHF) due to dilated cardiomyopathy (DCMP) of various etiology.
Material and methods. Patients (n=69) with DCMP of different etiology were included into the open randomized study. Idiopathic DCMP (IDCMP) was diagnosed in 26 patients and alcoholic cardiomyopathy (ACMP) - in 43 patients. Patients of IDCMP and ACMP groups were randomized for treatment with perindopril (groups 1 and 3, respectively) or carvedilol (groups 2 and 4, respectively). Follow-up was 6 months. End-diastolic and end-systolic left ventricular volume, stroke volume index, ejection fraction (EF) and exercise capacity were determined at baseline and in 2 and 6 months of treatment. Safety of the treatments was also assessed.
Results. Group 1: the average CHF class (NYHA) decreased by 20.7% (p<0.01), EF increased by 18.2% (p<0.05). Group 2: the average CHF class decreased by 29.6% (p<0.01), EF increased by 18.2% (p<0.05). Group 3: the average CHF class decreased by 14.3% (p<0.01), EF increased by 19.6% (p<0.05). Group 4: the average CHF class decreased by 41.4% (p<0.001), EF increased by 32.8% (p<0.001).
Conclusion. Monotherapy with carvedilol in patients with ACMP was more effective than this with perindopril. Long-term monotherapy with perindopril or carvedilol in patients with DCMP was well tolerated and safety.
640-649 4870
Ambiguous data about comparability regarding clinical outcomes for prehospital thrombolysis, coupled with timely coronary angiography, and primary percutaneous coronary intervention (PCI) in the early after acute ST-segment elevation myocardial infarction (STEMI), there are now.
In the STREAM trial 1892 patients with STEMI diagnosed within 3 hours after onset of symptoms, and whom it was impossible to perform primary PCI within 1 h after the first medical contact, were randomly assigned into two treatment groups: a) primary PCI b) prehospital thrombolytic therapy with bolus tenecteplase (dose decreased by half in patients aged ≥75 years) in combination with clopidogrel and enoxaparin followed by admission to the hospital, where it was possible to perform PCI. Emergency coronary angiography performed if thrombolysis failed. Coronary angiography and PCI of the infarct-related artery were performed in the period from 6 to 24 hours after randomization and thrombolytic therapy in the case of an effective thrombolysis. Primary endpoints include a composite of death, shock, congestive heart failure, or reinfarction up to 30 days.
The primary endpoint occurred in 116 of 939 patients (12.4 %) of the thrombolysis group and in 135 of 943 patients (14.3%) of the primary PCI group (relative risk in the group thrombolysis 0.86, 95% confidence interval 0.68-1.09, p=0.21). Emergency angiography was required in 36.3% of patients in the thrombolysis, and the remaining patients, coronary angiography and PCI were performed at a mean of 17 hours after randomization and thrombolytic therapy. Thrombolysis group had more intracranial hemorrhages than primary PCI group (1.0% vs 0.2%, p=0.04; after correction protocol and dose reduction by half of tenecteplase in patients ≥75 years: 0.5% vs. 0.3%, p=0.45). The rate of non- intracranial bleeding in two treatment groups did not differ.
Prehospital thrombolysis followed by coronary angiography and timely PCI provide effective reperfusion in patients in the early stages of STEMI that was not possible to carry out primary PCI within 1 h after the first medical contact. Nevertheless, fibrinolysis was associated with a slight increase in the risk of intracranial bleeding.
650-654 555
Aim. To analyze gender differences in pharmacotherapy and outcomes of ST-elevation myocardial infarction (STEMI) in patients of cardiology hospital in real clinical practice. Material and methods. A continuous pharmacoepidemiological analysis was performed on the base of 153 records of patients with STEMI (men 102, women 51), consecutively admitted to the emergency department of cardiology hospital in the period from October 2010 to April 2011.
Results. Women were on average 10.6 years older than men, had significantly higher incidence of severe comorbid conditions and significantly fewer prescribed medications improving STEMI prognosis - thrombolytics (21% vs 50%; p<0.05), statins (20% vs 53%; p<0.05), beta-blockers (84% vs 91%; p<0.05) and dual antiplatelet therapy (21% vs 59%; p<0.05). Hospital mortality was significantly higher in women than this in men, at that mortality differences persisted for 12 months after discharge.
Conclusion. Older age, higher comorbidity rate, and lower treatment compliance with the current clinical recommendations in female STEMI patients in comparison with these in male STEMI patients contribute to higher hospital mortality and 12-month mortality after discharge in women with STEMI.
655-659 494
Aim. To study the effect of simvastatin added to standard therapy on the left ventricular structure functional status in patients with diastolic chronic heart failure (CHF).
Material and methods. Patients (n=125) with diastolic CHF (relaxation disturbances and pseudonormalization) were included into the open nonrandomized study. Patients of the main group (n=66) received simvastatin additionally to standard therapy of CHF. Patients of control group (n=59) received standard therapy only. Initially and after 6 months of treatment Doppler echocardiography (EchoCG) was performed with assessment of transmitral blood flow indices. On the basis of EchoCG data diastolic dysfunction types were determined in patients of the main group. Dynamics of EchoCG indices were evaluated in accordance with these types.
Results. Significant increase in E (peak early diastolic left ventricular filling velocity) value by 14.1% (p<0.001) and E/A (where A - peak left ventricular filling velocity at atrial contraction) ratio by 18.7% (p<0.001) was found in the main group in estimating of transmitral flow indicators. Deceleration time of early diastolic filling significantly decreased by 7.8% (p<0.01). Other parameters did not change significantly both in the main and control groups. Intra-group comparison in the main group demonstrated that transmitral blood flow indices changed significantly only in patients with delayed relaxation (type I of diastolic dysfunction).
Conclusion. Simvаstatin added to standard therapy of CHF resulted in significant improvement in the left ventricle diastolic function.


660-663 595
In patients with arterial hypertension (HT) heart is affected earlier and more often than other target organs, left ventricular hypertrophy (LVH) develops. Considering the proven link between the presence of LVH and increased cardiovascular risk, the deterioration of the clinical course and prognosis in HT patients, as well as a significant prognosis improvement in patients with LVH decrease, correction of modifiable risk factors (including uncontrolled HT) is getting extremely important. Organoprotective properties of drugs should be taken into account as one of the important parameters in the consideration of antihypertensive therapy. Major studies conducted in recent years have proven cardioprotective and angioprotective properties of angiotensin receptor blocker losartan, so it can be used as first-line therapy in patients with HT and LVH.
664-671 571
Modern approaches to the choice of antihypertensive drugs are considered. Definitions of the "universal" combined antihypertensive therapy that can be effective in most hypertensive patients, regardless of their individual characteristics are discussed. Results of the most significant clinical trials evaluating the efficacy of combined antihypertensive therapy and the relevant provisions of up-to-date clinical recommendations are given as arguments.
672-677 616
The article deals with the problem of arterial hypertension in systemic vasculitis. Data on the principles of antihypertensive treatment of systemic vasculitis are presented. The possibilities of pharmacotherapy and surgical treatment of these diseases are discussed separately.
678-681 471
Current possibilities of AT1 receptor blockers (ARBs), such as candesartan, for optimization of antihypertensive therapy in stroke patients are presented in the article. ARBs are original drugs that effect to the delicate balance of pressor and depressor neurohormonal systems. They also have cerebroprotective action and are the drugs of choice for primary and secondary prevention of stroke in hypertensive patients
682-689 512
The review presents recent data on the usage of platelet functional tests in patients with ischemic heart disease after percutaneous coronary intervention and its contribution to antiplatelet therapy personalization and cardiovascular events frequency reduction.
691-697 759
Analysis of the data of national and international researches on evaluation of systemic inflammation in the acute coronary syndrome over the last 10 years was carried out. The problems of application the most studied inflammation markers in patients with acute myocardial infarction in clinical practice are focused.


698-700 731
The clinical significance of the SLCO1B1 gene polymorphism (encoding an organic anion transport polipeptide) in the development of statin induced myopathy is considered. Possible tactics of statin dose determination on the basis of pharmacogenetic testing is discussed. Indications for the use of this approach in clinical practice that should increase the efficacy and safety of the statin therapy are also considered.
701-707 664
On the basis of the analysis of published data the role of P-glycoprotein, carrier protein, in rational pharmacotherapy in cardiology was shown on the example of its substrates – digoxin, antiplatelet agents and anticoagulants. Determination of C3435T polymorphism of multidrug resistance gene (MDR1), encoding P-glycoprotein, in pharmacotherapy with digoxin, antiplatelet drugs (clopidogrel tikagrelol, prasugrel) and anticoagulants (dabigatran etexilate, rivaroxaban, edoxaban) is not feasible in routine practice. Drug in- teractions have clinical implications for the efficacy and safety of pharmacotherapy in coadministration of these drugs with P-glycoprotein substrates, inducers and inhibitors.


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ISSN 1819-6446 (Print)
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