Rational Pharmacotherapy in Cardiology

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Vol 6, No 6 (2010)
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779-788 712

Aim. To study efficacy and safey of sinus rhythm restoration with amiodarone and propafenone in outpatients with recurrent atrial fibrillation (AF), and to estimate pharmacoeconomic efficiency of such cardioversion in comparison with hospital treatment.

Material and methods. Patients (n=199; aged 59.2±1.36) with paroxysmal (73.9%) or persistent (26.1%) AF were included into the multicenter prospective study. Follow-up period was 13.14 months (min 1 month, max 36 months). Patients with arrhythmia relapse <48 h received outpatient cardioversion with amiodarone or propafenone orally. Daily outpatient examination, including ECG and blood pressure monitoring every 30-60 min, was carried out to evaluate efficacy of cardioversion and hemodynamics. Phone contact with patients was available. Patients with unstable hemodynamics received cardioversion in hospital. Patients received propafenone in cumulative dose of 600 mg (150-300 mg every hour), and amiodarone 600-800 mg daily. The cost/effectiveness ratio (CER) was estimated. This ratio shows the cost of one unit of effect.

Results. Outpatient cardioversion with amiodarone was started 24 h earlier (p=0.029) and with propafenone — 4.5 h earlier (p=0.002) than that in hospital. The average dose of amiodarone in ambulatory cardioversion was 1.3 times less (713.7±84,62 mg, p=0.345) than that in hospital cardioversion. Outpatient treatment with amiodarone restored sinus rhythm 8.7 h earlier, and with propafenone - 3.5 h earlier than the same treatments in hospital. Efficiency of hospital cardioversion with amiodarone was 70%, with propafenone - 80%, and efficiency of outpatient cardioversion — 96,1% and 98,4%, respectively. Outpatient treatment did not cause any severe side effects. Expenses for outpatient cardioversion made up 143 724.25 rubles, and for hospital cardioversion — 92 870.47 rubles. Average treatment costs for one patient in hospital was 6 times greater than for an outpatient. Outpatient cardioversion had the lowest CER (~1300 rubles%).

Conclusion. Outpatient cardioversion with amiodarone or propafenone is not only effective and safe, but also economically feasible.

789-795 434

Background. Effects of statins on cardiovascular end points are well-known. To study the impact of statins on structural and functional heart remodeling in patients with arterial hypertension (HT) seems

to be topical.

Aim. To study the effect of statins on cardiac remodeling in patients with HT.

Materials and methods. 120 patients with HT of 1 degree were included into the study: 56 men, 64 women, aged 52.4±10.23. Patients were randomized into 4 treatment groups: Group A1 (angiotensin converting enzyme (ACE) inhibitors + diet), group A2 (ACE inhibitor + fluvastatin), group B1 (angiotensin II receptor antagonist (ARA II) + diet), group B2 (ARAII + fluvastatin). Transthoracic echocardiography with calculation of standard left ventricle (LV) remodeling indices was performed.

Results. The most important prognostic markers of LV remodeling were revealed. They were a basis for definition of 3 types of early LV remodeling: type 1 — compensated, type 2 — adaptive, 3 type — maladaptive. After 6 months of treatment a number of patients in group A1 with type 2 and type 3 of LV remodeling reduced less (2%, p=0.02 and 4%, p=0.04, respectively) than this in group A2 (14%, p=0.04) and 4%, p=0.04, respectively). A number of patients with type 1 (compensated) of LV remodeling increased by 18% (p<0.001) in group A2, and by 6%, (p=0.03) in group A1. After the treatment a number of patients with type 3 and type 2 of LV remodeling decreased (p<0.001 and p=0.04, respectively) in groups B1 and B2 while a number of patients with type 1 of LV remodeling increased (p<0,001). A number of patients with type 1 of LV remodeling increased and this with type 3 of LV remodeling decreased in group B2 more prominently in comparison with group A2 (p=0.03; p=0.01, respectively).

Conclusion. Statins in patients with HT have cardioprotective effect that does not depend on basic antihypertensive therapy and total cholesterol level. In these patients combination of statins with ARA II has better cardioprotective effect than this with ACE inhibitors.

796-802 349

Aim. To compare the antiplatelet efficacy of the original and generic enterosoluble tableted acetylsalicylic acid (ASA) in patients with high cardiovascular risk.

Material and мethods. Patients (n=30) with high cardiovascular risk and indications for the ASA therapy were included in the study. Antiplatelet agents were withdrawn 3 weeks before study start (wash-out period). Study drugs were distributed at the start visit according to the randomization scheme. The first study drug course was 3 weeks, then next wash-out period lasting 3 weeks, and at last the second study drug course during 3 weeks occurred. Blood samples were taken; blood pressure and heart rate were recorded before and after therapies. ASA antiplatelet effect was evaluated by spontaneous and ADP-induced platelet aggregation assessment. Platelet aggregation was determined by the change turbidimetric translucent ability of the blood sample during the formation of aggregates after 2 minutes of exposure. ADP solution of three concentrations (0.5, 1 and 2 µMol) was used as an inductor of aggregation.

Results. Significant differences between the compared drugs in effect on platelet aggregation, blood pressure and heart rate were not found. Signs of platelet desaggregation after 3 weeks of generic ASA therapy were found in 65, 34.5 and 31% of patients when aggregation was tested with ADP 0.5, 1 and 2 µMol respectively. Desaggregation was revealed in 65.4, 42.3 and 31% of patients treated with original ASA (p>0.05) in the same test and the same ADP inducing concentration.. Adverse events associated with study drugs were not registered.

Conclusion. ASA generic Trombopol ® 75 mg (Pharmaceutical Factory Polpharma SA, Poland) and ASA original Aspirin® Cardio (Bayer AG, Germany) are equivalent in antiplatelet effect and tolerability.

803-811 361

Aim. To compare the effect of fosinopril and atenolol on synchronization of heart 0.1 Hz-rhythms and blood microcirculatory.

Material and methods. 63 patients at the age of 47±8 with hypertension (HT) of grade 1-2 were enrolled in the study. 0.1 Hz-oscillations in heart rate variability (HRV) and in filling of microcirculatory bed were registered during passive tilt test under spontaneous breathing. The duration of each stage of test was 10 min. Synchronization was estimated as a phase difference between 0.1 Hz-rhythms of heart rate and filling of microcirculatory bed. Frequency values of HRV spectrum in LF- and HF-ranges were also assessed.

Results. Fosinopril and atenolol showed comparable effect on blood pressure (BP) reduction. Atenolol decreased in heart rate significantly. Treatment with either fosinopril or atenolol in patients with significant vegetative dysfunction resulted in repair of functional interaction between heart 0.1 Hz-regulation and microcirculatory bed. Functional dissociation of 0.1 Hz-regulation mechanisms was observed under the treatment with fosinopril or atenolol in patients with initially sufficient interaction.

Conclusions. Fosinopril and atenolol influenced similarly on heart 0.1 Hz-mechanisms and microcirculation autonomic regulation in patients with HT. Atenolol is a drug of choice in patients with sympathicotony. Both drugs should be administered in according with an individual level of 0.1-Hz rhythms synchronization assessed before start of the treatment.

812-817 358

Aim. To evaluate short- and long-term prognosis of myocardial infarction (MI) depending on occurrence of pathologic Q-wave on ECG and time of its appearance.

Material and methods. 616 patients with initial ST-elevated MI were included into the study — 254 women and 362 men, aged 62.1±11.2. All patients were split up three groups depending on occurrence of pathologic Q-wave on ECG and time of its appearance. First group consisted of 311 patients with early Q-wave (during first 6 hours from onset of MI symptoms). Second group consisted of 120 patients with late Q-wave (from 6 to 24 hours from onset of MI symptoms). Third group consisted of 185 patients with non-Q-wave MI.

Results. The hospital lethality in the patients with early Q-wave was significantly higher than this in patients of the second and the third groups. However, we didn’t reveal significant differences between patients with late Q-wave and patients without Q-wave on ECG. The incidences of cardiac death (sudden death and fatal MI), non-fatal MI and hospitalization because of unstable angina was assessed during next two years. During the follow-up period patients of three groups had similar incidences of the non-fatal MI and hospitalization because of unstable angina. However, incidence of cardiac death was significantly higher in early Q-wave group in comparison with non-Q-wave group.

Conclusion. Occurrence of pathologic Q-wave on ECG and time of its appearance should be taken into account to assessed short- and long-term prognosis of MI.
818-822 518

Aim. To study the features of cardiac remodeling in patients with dilated cardiomyopathy (DCM) and postinfarction cardiosclerosis (PICS), that can be used for differential diagnosis of these diseases.

Material and methods. Patients with DCM (27 men and 5 women; aged 43.1±2.3) and patients with PICS (62 men; aged 56.4±1.1) and chronic heart failure (CHF) were included in the study. The diagnosis of DCM was based on clinical investigation, which also includes coronary angiography. The diagnosis of DCM in 19 patients was proven by the results of postmortem investigation. The diagnosis of PICS was based on documented history of myocardial infarction, ECG and echocardiographic sings. Echocardiography was performed in all patients and 14 healthy volunteers.

Results. End-systolic size (ESS) of left ventricular (LV) in patients with DCM and PICS at I (respectively 7.60±0.17 and 7.94±0.18 cm), IIA (7.66±0.28 and 8.64±0.30 cm) and IIB stages of CHF (8.26±0.28 and 8.94±0.15 cm) was significantly more than this in healthy volunteers (6.36±0.16, all p<0.01). ESS of right ventricular (RV) in DCM patients of the same CHF stages (respectively 7.21±0.22, 7.40±0.27 and 8.23±0.27 cm) is also more than this in healthy volunteers (5.95±0.17, all p<0.01). ESS RV in PICS patients at I (5.40±0.11 cm) and IIA (5.80±0.26 cm) CHF stages did not differ from healthy volunteers, and this index risen to IIB stage (6.62±0.21 cm), but was lower than in DCM patients.The ESS LV/ESS RV ratio at any CHF stage in PICS patients was significantly higher than this in DCM patients (1.48±0.04 and 1.06±0.02, 1.50±0.05 and 1.04±0.02, 1.37±0,06 and 1.00±0.01, respectively).

Conclusion. The ESS LV/ESS RV ratio can be used for differential diagnosis of dilatation in DCM and PICS patients.

823-827 413

Characteristics of amiodarone in clinical practice are focused on. Amiodarone pharmacological mode of action and its pro-arrhythmic effect is presented. As well as various side effects that can happen in clinical practice. Special attention is paid to the problem of amiodarone-induced thyrotoxicosis, its classification, diagnosis and treatment. Prospects of new anti-arrhythmic drugs class III, in particular dronedaron are also discussed.

828-831 363

Aim. To study the effect of the antidepressant paroxetine on the compliance to antihypertensive therapy in patients with arterial hypertension (HT) and post-stroke depression.

Material and methods. Patients (n=24) aged 55-73 with controlled HT (blood pressure, BP<140/90 mm Hg) and with subclinical poststroke depression after rehabilitation course were included into the study. Patients were split into two groups. Patients of group 1 (n=12) received adequate antihypertensive therapy and selective serotonin reuptake inhibitor paroxetine. Patients of group 2 (n=12) received antihypertensive therapy only. The study duration was 16 weeks. Patient compliance to antihypertensive therapy, BP and severity of depressive disorders, motor and intellectual functions was evaluated initially and after 16 weeks.

Results. BP>140/80 mmHg after 16 weeks was found in 10 (41.6%) patients. Clinical post-stroke depression was found in 7 (30.4%) patients, 5 (41.6%) of them were from group 2 (OR=0.35, 95% CI 0.12-0.78). High treatment compliance was in 15 (65.2%) patients, and 9 (81.8%) of them were from group 1. Nine (39.1%) patients did not receive an adequate antihypertensive therapy, 5 (41.6%) of them were from group 2 and could not explain their refusal from medication. General index of intellectual function was higher in patients of group 1 (p=0.034) than this in group 2; index of motor function did not change significantly (p>0.05).

Conclusion. Reduction of compliance to antihypertensive therapy and rehabilitation in hypertensive patients after stroke is associated with unmotivated refusal from treatment because of clinical post-stroke depression.

832-836 473

Aim. To compare the effects of fixed combinations of angiotensin converting enzyme inhibitor (enalapril) or angiotensin II receptor antagonist (losartan) with diuretic (hydrochlorothiazide, HCT) on the "office" blood pressure (BP) level in patients with arterial hypertension (HT) of 2-3 degrees.

Materials and methods. Patients (n=73; 34 men and 39 women; aged 50.5±5.8) with HT of 2-3 degrees were included in the study. Patients were randomized into 2 groups: patients of group 1 (n=34) received a fixed combination of enalapril with HCT; patients (n=39) of group 2 — a fixed combination of losartan with HCT. The study duration was 24 weeks. "Office" BP levels (Korotkov method) were evaluated.

Results. Combination of losartan with HCT shown more prominent effect on systolic BP (reduction from 176.1±2.77 to 122.3±1.54 mm Hg) in comparison with combination enalapril with HCT (reduction from 172.4±1.62 to 129.8±3.4 mm Hg) after 12 weeks of treatment (p<0.05). High frequency of target BP level achievement was observed in patients of groups 1 and 2 (83% and 86% respectively).

Conclusion. The fixed combination of enalapril or lozartan with HCT has high efficacy and can be recommended as initial therapy in patients with HT of 2-3 degree.


837-842 459

Possibilities to use and advantages of a new tissue plasminogen activator (tenekteplase) in patients with acute coronary syndrome (ACS) with ST segment elevation are discussed. The main factor of tenekteplase successful implementation is the time. Comparative studies of tenekteplase and other tissue plasminogen activator are presented. Efficacy of thrombolytic therapy and percutaneous coronary interventions is compared. Data from multicenter randomized clinical trials about combined use of tenekteplase and enoxaparin and unfractionated heparin in the hospital is discussed. Data about safety of tenekteplase in treatment of ACS with ST segment elevation is given.

843-852 336

The classic hypoglycemic agents include biguanides, sulfonylurea drugs, meglitinides, glitazones and alpha-glucosidase inhibitors. Modern algorithm of hypoglycemic therapy in the first step considers lifestyle modification and metformin monotherapy, the second step — the combined therapy. However, the effect of combined hypoglycemic therapy on long-term cardiovascular prognosis in patients with type 2 diabetes mellitus is studied insufficiently. Combined therapy with glibenclamide and metformin can result in adverse cardiovascular effects, so that long term therapy should be avoided in patients with coronary heart disease. Adequate pharmacological approaches to hyperglycemia correction should be elaborated.

853-858 439

Published data often contain conflicting views on the relationship of retina changes in arterial hypertension (HT) with cardiovascular disorders and target organs lesions. Along with the classification and pathophysiology of hypertensive retinopathy, evidence for its association with the HT course, target organ lesions and prognosis is presented. Functional disorders of the eyes point at the involvement of retina into the pathological process even in HT early stages and are able to reflect the severity of hypertension. This supports a close relationship of HT with eye disease as a target organ. Available data support also possibility to assess changes on the eye fundus in patients with uncomplicated HT, indicating that it was premature decision to exclude eyes from the list of target organs in HT.

859-864 457

Data of evidence-based cardiology and clinical guidelines that define the position of combined therapy to achieve the targets of hypertension (HT) treatment (achievement and maintenance of the target blood pressure (BP) level, protection of the target organs, improvement of the quality of life in hypertensive patients) are presented in the article. The advantages of rational combined therapies (potentiation of antihypertensive effect, reduction of a number of adverse events) are considered. Studies of therapeutic efficacy and safety of combined antihypertensive therapy based on generics are important. The advantages of combined therapy in achievement of target BP levels are presented on example of comparative study of new generic and original amlodipine in patients with HT of 1-2 degrees. Target BP level was reached respectively in 90% and 97% of patients with HT in groups of generic and original amlodipine combined with generic lisinopril and hydrochlorothiazide. Safety profile was acceptable. This confirms the high efficacy of amlodipine + lisinopril + hydrochlorothiazide combination, including one on the basis of generics.


865-869 438

The possibility to stabilize and reverse the atherosclerotic plaques in coronary arteries due to therapy with atorvastatin and rosuvastatin was demonstrated in recent studies. The advantage of aggressive lipid-lowering therapy compared with standard therapy is proven in patients with both stable and acute forms of ischemic heart disease (IHD). Pleiotropic effects, in particular, effect on endothelial function, ability to reduce the blood level of C-reactive protein are important in the statins mode of action. Risk reduction of cardiovascular complications and slow down of atherosclerosis progression in patients with IHD was significantly associated with decrease in levels of both atherogenic lipids and C-reactive protein.

870-875 342

Highlights of primary prevention of death in patients with ventricular arrhythmias (VA) are discussed. Overview of all main clinical trials exploring various anti-arrhythmic drugs in prevention of death in patients with VA is presented. It is emphasized that in patients with organic heart disease and VA only beta-blockers and amiodarone are able to reduce mortality, while other drugs have no effect on mortality, or they even increase mortality mainly due to arrhythmogenic effect. Recent clinical studies of the cardioverter-defibrillators efficacy in these patients are presented. It is shown that the use of cardioverter defibrillators compared with pharmacotherapy is more effective in prevention of fatal outcomes.

876-881 335

Basic principles of beta-blockers choice strategy are presented. Attention is focused on the facts concerning the evidence base for effects of various beta-blockers on the outcomes of cardiovascular diseases. Beta-blocker indications and safety of their long-term use are considered from this point of view. Convincing data about beta-blocker impact on the prognosis of cardiovascular disease should be the reason for any beta-blocker choice, as well as choice of their doses which were tested in large randomized trials.

882-887 339

Methylated analogs of L-arginine - asymmetric dimetilarginin (ADMA) and monometilarginin (L-NMMA) - are endogenous inhibitors of endothelial NO-synthase (eNOS). ADMA level in maternal plasma is increased in women with preeclampsia. The high level of ADMA is one of the predictors of preeclampsia. L-arginine increases the activity of eNOS and production of nitric oxide in the ADMA-similar model of L-NAME-induced endothelial dysfunction. ENOS activator (resveratrol), antioxidants, potentiated polyclonal antibodies to eNOS and others agents have been effective in this model. Studies of endotelioprotective activity in other «ADMA-eNOS-associated" experimental models of metabolic syndrome and homocysteine-induced, gipoestrogen-induced sepsis-induced endothelial dysfunction and endothelial dysfunction in postvaccinal vasculitis have been developed.

888-901 314

Therapy for ST-segment elevation myocardial infarction patients who present late or are ineligible for reperfusion.


938-939 173

Report on holding of Russian National Congress of Cardiology, October 5-7, 2010.

940 179

Working group of the Young Cardiologists has been established at the Society of Cardiology of the Russian Federation.

941 182

X Russian scientific Conference with International Participation “Rehabilitation and Secondary Prevention in Cardiology”, May 18-19, 2011, Moscow.

942-943 168

National Award in Cardiology “Purple heart” will be Bestowed to the best Cardiac Surgeon.

944-947 188

Index of the Papers Published in the “Rational Pharmacotherapy in Cardiology” Journal in 2010.

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