Rational Pharmacotherapy in Cardiology

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Vol 15, No 2 (2019)
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149-158 721

Aim. To identify predictors of progression of atrial fibrillation (AF) in patients with hypertension (HT), coronary heart disease (CHD) and chronic heart failure (CHF) with recurrent AF.

Material and methods. The study included 31 2 patients with recurrent AF. The patients were divided into 3 groups according to a leading underlying condition: essential HT (n=1 36), CHD (n=11 2), and CHF with III-IV functional class by NYHA (n=64). The average follow-up duration was 60±3 months. Progression of AF was defined as development of long-standing persistent or permanent AF.

Results. All three groups of patients with recurrent AF revealed progression of the arrhythmia from paroxysmal or persistent to a sustained permanent form during the 5-year prospective follow-up. The rate of AF progression in the patients with CHF was significantly higher and accounted for 59% as compared to 46% in the patients with hypertension (p=0.002) and 51% in the patients with CHD (p=0.008). AF progression in patients with HT correlated significantly with left ventricular (LV) hypertrophy (odds ratio [OR] 1.25; 95% confidence interval [95%CI] 1.03-1.52) and increased arterial wall stiffness (OR 2.3; 95%CI 1.95-2.65). The independent predictors of arrhythmia progression in patients with CHD were a history of myocardial infarction (OR 1.23; 95%CI 0.9-1.5), irreversible LV wall motion abnormalities (OR 1.41; 95%CI 1.1-1.7), and increased plasma level of N-terminal pro-A-type natriuretic peptide (Nt-proANP; OR 1.16; 95%CI 0.8-1.4). Reduction in LV ejection fraction below 40% (OR 0.84; 95%CI 0.7-0.89) and increased plasma N-terminal pro-B-type natriuretic peptide (Nt-proBNP; OR 2.3; 95%CI 1.93-2.67) were independent predictors of AF progression from persistent to permanent form in the patients with systolic heart failure.

Conclusion. Progression of AF is related to the underlying cardiovascular disease. The early vascular aging syndrome and LV hypertrophy are the main factors of AF progression in patients with HT. Previous myocardial infarction with irreversible hypokinesia is associated with AF progression in patients with CHD. Reduced LV ejection fraction and increased plasma BNP predict AF progression in patients with CHF.

159-165 653

Aim. To study markers of renal dysfunction in relation to the likelihood of atrial fibrillation (AF) in patients after ST-segment elevated myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI).

Material and methods. The study was conducted with the inclusion of 1 52 patients discharged for outpatient monitoring after STEMI. There were 4 visits: V1 - inclusion visit, V2 - in 12 months, V3 - in 18 months, V4- in 24 months with determination of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP), cystatin C, erythropoietin, galectin-3, von Willebrand factor (fW), left ventricular ejection fraction. Endpoint: new cases of AF, cardioembolic stroke, deaths.

Results. After 24 months 35 patients (23.0%) were diagnosed with AF, 6 of them (3.9%) - developed cardioembolic stroke. The multivariate model of risk factors for AF included indicators: cystatin C (odds ratio [OR] 1.31; 95% confidence interval [95%CI] 1.03-1.67), NT-ProBNP (OR 1.11; 95%CI 1.03-1.19), galectin-3 (OR 0.71; 95%CI 0.55-0.91), fV (OR 0.71; 95%CI 0.55-0.91).

Conclusion. The prognostic significance of cystatin C in relation to the risk of AF was established, which should be considered when assessing the prognosis in patients after STEMI.

166-173 1068

Aim. To assess efficacy and safety of single-pill combination (SPC) amlodipine/perindopril and amlodipine/indapamide/perindopril in patients with uncontrolled hypertension (HT) in routine clinical practice.

Material and methods. 16144 patients with uncontrolled HT were included into this multicenter observational study. Eventually 6% of patients were excluded owing to violations of protocol. 15193 patients became subjects to the final statistical analysis; they all were prescribed with single-pill combination amlodipine/perindopril or amlodipine/indapamide/perindopril and subsequently purchased these drugs. Study lasted for 3 months; during this time researchers performed office blood pressure (BP) and heart rate measurements on a monthly basis. Additionally, the researchers registered adverse effects and assessed efficacy and safety using 7-point scale.

Results. Initially, patients had an average systolic BP of 1 64.2 ± 1 1.4 mm Hg, diastolic BP - 94.8±8.1 mm Hg, and they also had antihypertensive therapy in 85-89% of cases (in different regions). Patients received ACE inhibitors in 50-54% of cases, angiotensin receptor blockers - in 1 9-23%, calcium channel blockers - in 24-31 %, thiazide diuretics - in 29-36%, beta-blockers - in 27-32%. Monotherapy with ACE inhibitors was used in 1 2-18% of patients, and monotherapy with other antihypertensive drugs - in 1 -4%. Mean age was 60.5 years, mean body mass index - 29.3 kg/m2, 43% of patients had a very high risk by SCORE scale. Prescribed therapy: SPCs amlodipine/perindopril (54%) and amlodipine/indapamide/ perindopril (46%) in different doses. By the end of treatment course, the following results have been got: 88% of patients achieved target BP levels (92% and 85% among patients who took SPCs amlodipine/perindopril and amlodipine/indapamide/perindopril, respectively). Systolic BP decreased by 36,6±11,4 mm Hg (22.0±5.9%), diastolic BP - by 15.6±8.5 mm Hg (16.0±8.1%), pulse BP decreased by 21.0±11.4 mm Hg (28.8±13.9%). Mean efficacy assessment rate was 6.9±0.37 points out of 7; mean safety assessment rate was 6.9±0.37 points out of 7. Adverse events were recorded in 257 patients, which constituted 1.7% of the entire patients' population.

Conclusion. Using SPC amlodipine/perindopril and amlodipine/indapamide/perindopril is associated with fast achievement of the target BP levels among most patients with a small number of adverse effects.

174-179 902

Increased thyroid stimulating hormone (TSH) levels are detected quite often especially in older patients. Increased TSH level doesn't usually indicate the formation of persistent hypothyroidism and may be due to concomitant somatic disorders. Determining the threshold values of TSH associated with cardiovascular diseases (CVD) is an important clinical task.

Aim. To study the detectability of subclinical hypothyroidism, the range of thyroid-stimulating hormone values associated with CVD in patients who seek medical care at the multidisciplinary hospital of the North-West region.

Material and methods. 1340 patients of different sex and age with normal TSH value (0.4-2.5 mlU/l) and subclinical hypothyroidism were included into the study. Subclinical hypothyroidism was considered an increase in TSH level >4.0 mlU/L, provided that the level of free T4 is normal. According to electronic case histories in all patients, CVD (hypertension, coronary heart disease, heart failure, arterial atherosclerosis of the lower extremities) and a history of cardiovascular events (unstable angina, acute myocardial infarction, stroke and transient ischemic attack) were analyzed. For data processing the program Statistica, version 1 2 was used.

Results. The detectability of subclinical hypothyroidism was 1 0.2%, manifest hypothyroidism - 2.4%. In patients with subclinical hypothyroidism, CVD were detected significantly more often than in patients with euthyroidism (p<0.05). Subclinical hypothyroidism increased the likelihood of CVD in the middle age group (odds ratio [OR] 1.62; 95% confidence interval [95%CI] 1.39-1.89), in elderly patients (OR 3.84; 95%CI 2.95-4.99), and in patients 75 years and older (OR 2.53; 95%CI 1.84-3.50). Using the discriminant analysis, a mathematical model was built which allows predicting the development of CVD according to the TSH level of (accuracy - 66.7%, sensitivity - 22.3%, specificity - 96.8%). The estimated threshold TSH was 6.68 mlU/L. Patients with TSH levels <6.68 mlU/L have a high probability that they are healthy (96.8%), and elevated TSH levels (<6.68 mlU/L) are probably not associated with CVD.

Conclusion. An association of subclinical hypothyroidism with coronary heart disease, hypertension and CVD in general has been established. A TSH level of less than 6.68 mlU/L is probably not associated with CVD and does not require active treatment.

180-190 598

There is limited information on the comparative results of using different thrombolytic drugs for pharmacoinvasive reperfusion in acute ST-segment elevation myocardial infarction (STEMI). There is special interest in comparing the efficacy of fibrin-selective and fibrin-non-selective thrombolytics.

Aim. To study the prevalence of major adverse cardiovascular events and the status of patients who had STEMI and pharmacoinvasive reperfusion a year ago, depending on the choice of thrombolytic drug.

Material and methods. 240 STEMI-patients undergoing pharmacoinvasive reperfusion (reference event) were divided into 4 groups depending on the choice of the thrombolytic drug (alteplase [group 1], teneteplase [group 2], fortetelizin [group 3], streptokinase [group 4]) as well as into 2 groups depending on the fibrin-specificity of thrombolytics. One year after the reference event the prevalence of major cardiovascular events (death, repeated myocardial infarction, stroke, repeated revascularization of the target vessel, and their combination) was assessed. Data of echocardiography and 24-hour ECG monitoring, indicis of rating scale of clinical state in patients with heart failure (RSCS, Mareev V.Y, 2000), results of determination of plasma N-terminal pro-B-type natriuretic peptide (NT-proBNP) and of six-minute walk test were also analyzed.

Results. One year after the reference event, patients who received fibrin-selective thrombolytics (groups 1,2, 3) compared with patients treated with fibrin-non-selective drug (group 4) had a higher left ventricular ejection fraction (49.8±7.4% vs 47,4±6.8%; p=0.048), lower index of impaired local contractility (1.19 [1.06; 1.38] vs 1.25 [1.175; 1.5], p=0.029), an end-diastolic volume (1 39.1 ±28.6 ml vs 148.7±23.9 ml; p=0.027), the size of the left atrium (39.0±4.6 mm vs 41.1 ±3.1 mm, p=0.007 ), and insignificantly lower prevalence of atrial fibrillation (1.5% vs 6.7%, p=0.068). They also showed a lower prevalence of supraventricular tachycardia (4.5% vs 13.3%, p=0.049) and ventricular extrasystoles (54.5% vs 76.7%, p=0.022) as well as the daily number of ventricular extrasystoles (4.5 [0; 32.0] vs 34, 0 [2.25; 80.25], p=0.001) with more favorable gradations and indicators of heart rate variability. Statistically significantly lower NT-proBNP level (148 [1 20; 208.5] pg/ml vs 241 [189; 287] pg/ml; p=0.000) and chronic heart failure manifestation according to RSCS (p=0.033), as well as a longer distance in the six-minute walk test (p=0.000) were found in patients treated with fibrin-selective drugs. Statistically significant differences between groups 1, 2, 3 for the study period were not found. Significant differences in the prevalence of hard clinical endpoints (death, repeated myocardial infarction, stroke, repeated revascularization of the target artery) were not found in all groups.

Conclusion. More favorable clinical, laboratory and instrumental parameters were found one year after STEMI and pharmacoinvasive reperfusion with fibrin-specific thrombolytic agents as compared with fibrin-non-specific thrombolytic. All groups had no statistically significant differences in the effect on hard clinical endpoints during the entire observation period.

191-197 563

Aim. To study the pharmacoepidemiological features of the prescription of antihypertensive fixed dose combinations and their efficacy in hypertensive patients in the real outpatient practice in Vladivostok city.

Material and methods. Hypertensive patients aged 1 8 years and older (n=268) observed in Vladivostok polyclinics from October to December 2017 were included into the study. All patients did not have target blood pressure (BP) levels. The analysis of the medical prescriptions of antihypertensive fixed dose combinations in Vladivostok polyclinics was performed. Two-component (perindopril + amlodipine) or three-component (perindopril + amlodipine + indapamide) fixed dose combinations were prescribed by physician in accordance with instructions for medical use and their pharmacological characteristics. The study was non-interventional and included 3 visits for the initial examination, prescription and correction of therapy, considering its efficacy. All patients were determined for glomerular filtration rate using CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration Formula), changes in BP. Patients performed self-esteem on a 1 0-point visual analogue scale (VAS).

Results. Only 23.4% of patients reached target BP levels in the first month of observation, and 84.5% of patients after 3 months of observation. 30 (1 1.2%) patients had replacement with double antihypertensive fixed dose to triple combination combinations during the study. 68.6% of patients did not have a replacement for the initial prescribed antihypertensive fixed dose combinations due to the achievement of target BP. The number of patients with moderately and markedly reduced glomerular filtration rate was reduced significantly. Initially, the patients included into the study assessed health (according to adapted VAS) for 5.6±1.4 points, and after 3 months of follow-up - for 7.9±1.7 points.

Conclusion. The use of antihypertensive fixed dose combinations containing ACE inhibitor (perindopril), calcium channel blocker (amlodipine) and thiazide-like diuretic (indapamide) resulted in achievement of target BP levels in 84.5% of patients after 3 months of follow-up. Also, the use of double and triple fixed dose combinations had a nephroprotective effect, manifested in an increase in the number of patients ( + 19.3%) with a glomerular filtration rate more than 60 ml/min/1,73м2 and a positive effect on the patient's well-being.


198-203 627

A long-term clinical observation of the patient with ventricular tachycardia induced by exercise test but without myocardial ischemia and coronary artery atherosclerosis based on the results of angiography in the debut of the disease is described. However, arrhythmia reproducibility during stress tests, positive drug tests with nitroglycerin and beta-blocker, results of cardiac positron emission tomography with fatty acids revealed the ischemic genesis of arrhythmias, which was indirectly confirmed by a positive antiarrhythmic effect of the therapy with a metabolic drug (treatment with a beta-blocker was impossible because there was a sinus block). Coronary angiography was performed again after 7 years during the recurrence of ventricular arrhythmia with unstable angina. Stenosis of the left anterior descending artery was revealed. The antiarrhythmic effect of myocardial revascularization was continuously positive. Therefore, ventricular tachycardia induced by exercise test in patients with risk factors even in the absence of clinical and electrocardiographic criteria for myocardial ischemia could be an early debut of coronary artery disease.


204-208 522

Aim. To study some structural and functional indicators of the right heart, as well as the effect of antiviral therapy on these parameters in patients with viral liver cirrhosis (VLC).

Material and methods. Patients with VLC (n=98; mean age 40.6 years, disease duration 3.9 years) were examined. The patients were divided into 2 groups: without ascites (1 st group; n=59) and with ascites (2nd group; n=39). The control group included 22 healthy volunteers. All participants had standard and tissue Doppler echocardiography.

Results. The thickness of the anterior wall of the right ventricle (RV) was increased in the 1 st and 2nd groups compared with the control (by 20% and 27%, respectively), as well as the volume index of the left atrium. The decrease in the rate of early RV filling (E) and the E/A ratio was found: in the 1st group - 0.9 [0.8;1.31 ], in the 2nd group - 0.8 [0.78; 1.2] with a control value of 1.6 [1.2;1.94] (p<0.001). Patients of the 2nd group compared with the control group and patients of the 1st group showed an increase in myocardial productivity index (by 35% and 35%, respectively) and time of isovolumetric RV filling (by 32% and 29%, respectively). RV dilatation, an increase in the index of the volume of the left atrium, dilatation of the pulmonary artery and an increase in systolic pressure in the pulmonary artery (in 2nd group - 36 [26;39] mm Hg, in 1 st group - 28 [1 9;32] mm Hg, in control - 24 [11 ;26] mm Hg; p<0.001) were also found in the 2nd group. The decrease in the maximum systolic velocity of the fibrous ring of the mitral valve in comparison with the reference level was found in 21 (36%) VLC patients with ascites and in 6 (1 6%) without ascites. The use of antiviral therapy led to a decrease in the left atrial volume index and systolic pressure in the pulmonary artery. A correlation was found between pressure level in the pulmonary artery and the Tei index (r=0.74; p<0.001), the systolic velocity of movement of the fibrous ring of the mitral valve (r=0.54; p<0.001), the diastolic velocity Em (r=0.72; p<0.001), blood flow velocity in the own liver artery (r=0.63; p<0.001) as well as the maximum systolic velocity in the portal vein (r=0.61; p<0.001).

Conclusion. Structural and functional changes in the right heart and left atrium were found in VLC patients. These disorders depend on the degree of decompensation of the hepatic process and are more pronounced in patients with ascites. Antiviral therapy had a positive effect on some morpho-functional parameters of the heart. The found correlations indicate the effect of hepatic-portal blood flow on cardiohemodynamic disorders.


209-214 1310

Aim. To perform an arterial hypertension (HT) screening for assessing the awareness of Moscow Region citizens about high blood pressure (BP) and draw their attention to this important risk factor.

Material and methods. The screening was performed as a part of Standardized International Screening Study "May Measurement Month 2018” in five towns of Moscow Region: Domodedovo, Balashikha, Mytishchi, Solnechnogorsk, Klin. 510 participants (324 females, 186 males) were involved, aged from 18 to 86 years (median age 42 [28;57] years). People over 1 8 years were asked to measure BP levels and fill out a questionnaire: age, gender, height and weight, previous BP measurement date, bad habit (tobacco smoking, alcohol consumption), cardiovascular diseases and type 2 diabetes history, previous high BP levels and antihypertensive drugs taking. Elevated BP was considered systolic BP (SBP) ≥140 mm Hg and/or diastolic BP (DBP) ≥90 mm Hg. Mechanical and automatic tonometers were used.

Results. Increased BP was registered in 24% of participants. High BP levels were more common among men of working age and women older than working age. Increased BP was registered for the first time in 7% of the participants, and half of the participants who had previously taken antihypertensive therapy had increased BP levels. The highest prevalence of elevated BP levels was detected in obese men (55%).

Conclusion. Regular preventive medical examinations have the task of health keeping and timely disease prevention. The continuity in the medical care may reduce the incidence of socially significant diseases.

215-223 1090

Aim. To perform a comparative analysis of cardiovascular medicine prices in 2011 and 2015 and to assess their availability and affordability as a basis for rational pharmacotherapy.

Material and methods. We conducted a comparative analysis of prices for cardiovascular medicines in 2011 and 201 5 in Kazan using the World Health Organization and Health Action International (WHO/HAI) methodology, to assess medicines' availability and affordability to ensure their rational use. We studied availability and prices of 71 cardiovascular medicines in public and private pharmacies of the city of Kazan and analyzed procurement prices of these medicines in hospitals. Also we performed pharmacoeconomic cost-minimisation analysis for arterial hypertension pharmacotherapy in 2015. For each medicine, we analyzed the prices for the original brand drug and its lowest-priced generic. We compared medicine prices with international reference prices of 201 0 and 201 5, delivered by the Management Sciences for Health, by expressing them as median price ratio. Recording and analysis were performed using the standardized MS Excel WHO/HAI Workbook.

Results. The prices of generic medicines, both in the public and private sectors, decreased relative to reference prices in 2015 compared to 2011. In 201 1 one third of the medicines were purchased as original brands and in 201 5 almost all medicines were procured as generics with a fourfold decrease in prices. In 201 5, depending on the choice of the medicine the annual course of monotherapy of hypertension varied from 208 to 281 05 rubles.

Conclusion. Over the five years from 2011 to 2015, there was a general trend of price reduction for generic products relative to reference prices for cardiovascular medicines. But in order to provide rational pharmacotherapy, additional price studies and pharmacoeconomic analyzes are needed, taking into account the changing prices on the pharmaceutical market.


224-229 530

Background. The prognosis for patients after acute myocardial infarction (AMI) can be improved by prescribing beta-blockers (BB), angiotensin converting enzyme inhibitors (ACEI) and statins. This is reflected in the current clinical guidelines, in which these drugs are considered mandatory for almost all patients after AMI. However, not all representatives of the same drug class have the same evidence base in relation to the impact on the outcomes of AMI, in addition, not all BB and ACEI, according to the official instructions have the indication "recent AMI".

Aim. To assess the adequacy of the choice of BB, ACEI and angiotensin receptor antagonists (ARA), prescribed after recent AMI, using the materials of the prospective registry PROFILE-IM.

Material and methods. 1 60 patients after AMI referred to outpatient clinic from March 01,2014 to June 30, 201 5 were included into the registry. The therapy prescribed to patients at discharge from the hospital and at the first visit to the outpatient clinic were evaluated, special attention was paid to three classes of drugs: BB, ACEI/ARA.

Results. The majority of patients were recommended ACEI/ARA (88.1%) and BB (98.8%) at discharge from hospital. Not prescribing of these groups of drugs in about half of the cases had a reasonable cause, for ACEI/ARA in 13 patients (8.1%) the cause could not be clarified. When choosing a BB in most cases (both in hospital and in the outpatient clinic) preference was given to bisprolol (61% and 67%, respectively), which has no evidence of prognosis improvement for patients after AMI, the second place took metoprolol, its prescription was two times less than bisprolol. When choosing ACEI, priority was given to perindopril, with which no one randomized clinical trial was carried out in patients after AMI (38% of prescriptions in the hospital and 41% - in the outpatient clinic). Enalapril took the second place (20% and 22%, respectively), the remaining ACEI were prescribed much less frequently, ARA were also prescribed rarely (5%).

Conclusion. After AMI the majority of patients were prescribed BB, ACEI/ARA, which in accordance with current clinical guidelines are necessary to improve long-term outcomes. However, the choice of a specific drug within the drug class not always consistent with evidence-based medicine, current clinical guidelines and the official instructions for the medical use. In this regard, patients after AMI do not receive all the benefits of drug therapy to improve long-term outcomes.


230-243 1224

The review discusses the problem of overweight, obesity and metabolic syndrome and their activating effect on the sympathetic nervous system and the increase in blood pressure. Current epidemiological data on the prevalence of obesity and metabolic syndrome and trends in their occurrence in recent decades are presented, indicating the high significance of these disorders in modern health care and their important role in development of the overall disease burden. In accordance with the clinical guidelines, types of obesity are described with a special focus on its abdominal type, as a factor that increases cardiovascular risk. The mechanisms of sympathetic overactivity in obesity, including insulin resistance, hyperleptinemia, the effect of nonesterified fatty acids, obstructive sleep apnea and baroreflex impairment are considered in detail. In the second part of the paper experimental and clinical findings are presented indicating worsening of the hypertension mediated target-organ damage in the presence of concomitant obesity that emphases on the crucial role of amplified adrenergic stimuli in the formation of these disorders. The promoting effect of obesity and concomitant sympathetic nervous system overactivation on the development of left ventricular hypertrophy, endothelial dysfunction and vascular damage, renal dysfunction and cognitive decline are considered. Finally, body of evidence of high antihypertensive efficacy as well as prominent target organ protective features of the highly selective β1-blocker bisoprpolol are presented especially when it prescribed in patients with arterial hypertension and concomitant obesity and metabolic syndrome.

244-250 811

Breast arterial calcification (BAC) is a type of calcification of the media of the middle and small arteries (Menkeberg's calcification). This distinguishes it from calcification associated with the atherosclerotic process and localized in the intima of the vessel. There are data on the association of BAC with cardiovascular diseases (CVD). This allows it to be considered as a new marker of cardiovascular risk in women. The purpose of the first part of the review is to analyze the current literature on the prevalence of BAC, factors related to its occurrence and the association of BAC with traditional CVD risk factors. The prevalence of BAC (data from cancer screening programs) is about 12.7%, and it increases with age to 50% in 80-year-old women. It is not an attribute of "healthy aging", but depends on race and ethnicity. There is a connection with reproductive function. The frequency of BAC increases with the number of children born, with breastfeeding, in menopause, and decreases during hormone replacement therapy. Smoking women have a BAC frequency 2 times less than non-smokers. Detection of BAC on mammograms is associated with conditions pathogenetically associated with CVD: an increase in the frequency of hyperlipidemia, diabetes, chronic kidney disease, a decrease in bone mass. There is a strong correlation of BAC with coronary calcium (indicator of coronary atherosclerosis). A statistically significant association of BAC with overweight, obesity, and smoking was not found, but there is a weak association with arterial hypertension. This may indicate an independent pathophysiological role of BAC in the development of vascular disorders and allows us to consider BAC as an independent marker for improving cardiovascular risk stratification in women. BAC is believed to be a marker of a more generalized trend towards the development of medial calcification in other vascular areas. This leads to a systemic increase in arterial stiffness and contributes to the development of CVD.

251-257 738

A recently published article [1 ] on the problems of anticoagulant therapy in patients with frailty syndrome contains two statements which highlight ri-varoxaban among other non-vitamin K antagonist oral anticoagulants (NOAC): 1) none of the randomized controlled trials (RCTs) with NOAC (except for two RCTs with rivaroxaban - EINSTEIN-DVT and EINSTEIN-PE) contained data on the participation of frail patients; 2) one of the studies of real clinical practice showed that only therapy with rivaroxaban (out of three NOAC) in comparison to warfarin reduced the risk of stroke/systemic embolism and ischemic stroke in frail elderly patients with atrial fibrillation after 2 years of observation. The paper presents a critical analysis of these statements showing that the first statement is based on the incorrect use of the collective term "fragility” as a synonym for the term "frailty”, whereas the second statement is based on the results of a study that has a number of serious methodological limitations.

258-264 923

Arterial hypertension (HT) is one of the main recognized risk factors for the development of cognitive impairment and dementia. The results of most studies indicate that the presence of HT in elderly and senile people is associated with a decrease in cognitive functions and an increased risk of dementia in people of this age group, although some studies have identified the so-called "U-shaped curve”. The state of cognitive functions in middle-aged patients with HT has been studied to a much lesser extent, but it has been established that the presence of HT in middle age is associated with deterioration of cognitive functions and an increased risk of dementia in the elderly. In middle-aged hypertensive patients, cognitive impairment affected all cognitive domens, but to a greater extent - neurodynamic indicators of cognitive functions (speech activity, ability to concentrate, speed of cognitive processes). There are few data that levels of systolic blood pressure (BP) during the day, during wakefulness and sleep periods, insufficient night BP decrease, increased daily BP variability, and increased magnitude of the morning BP rise are interrelated with deterioration of the control functions/speed of cognitive processes. Pathogenetic aspects of the relationship of cognitive impairment and HT are diverse and include the hyperactivation of neuro-humoral systems (renin-angiotensin-aldosterone and sympathoadrenal, hypothalamic-pituitary-adrenal system dysfunction, reduction of cerebral perfusion, endothelial dysfunction. Anxiety-depressive disorders are of great importance in the occurrence of cognitive impairment in patients with HT, their interrelation is complex, dualistic, possibly due to a decrease in brain perfusion.


A recently published article (Rational Pharmacotherapy in Cardiology 2018;6:908-16) on the problems of anticoagulant therapy in patients with frailty syndrome contains two statements which highlight rivaroxaban among other non-vitamin K antagonist oral anticoagulants (NOAC): 1) none of the randomized controlled trials (RCTs) with NOAC (except for two RCTs with rivaroxaban – EINSTEIN-DVT and EINSTEIN-PE) contained data on the participation of frail patients; 2) one of the studies of real clinical practice showed that only therapy with rivaroxaban (out of three NOAC) in comparison to warfarin reduced the risk of stroke / systemic embolism and ischemic stroke in frail elderly patients with atrial fibrillation after 2 years of observation. The paper presents a critical analysis of these statements showing that the first statement is based on the incorrect use of the collective term “fragility” as a synonym for the term “frailty”, whereas the second statement is based on the results of a study that has a number of serious methodological limitations.


265-270 767

Modern tactics of antihypertensive therapy with fixed dose combination or with free combinations of antihypertensive drugs are reviewed in the article. The evidence that a flexible regimen of combination antihypertensive therapy is more reasonable in the modern treatment of arterial hypertension is presented. The question of the characteristics of hypertensive patients in whom lowering blood pressure to lower target levels may be useful to improve the prognosis is discussed considering the results of the analysis of data on participants in a randomized clinical trial SPRINT. Approaches to reducing the incidence of adverse events caused by antihypertensive therapy in such patients in general and in elderly and senile patients who have not only a higher likelihood of achieving advantages of more intensive antihypertensive therapy regimens for influencing the prognosis, but also a higher risk of complications, due to therapy are considered. The problem of less high efficacy of using replicated antihypertensive drugs (generics) compared to the original drugs is discussed.

271-276 495

The question of the possibility of the most effective drug choosing within one class from the standpoint of evidence-based medicine is considered in the article. Drugs belonging to the same class may have both great similarities and significant differences. This is demonstrated by the example of different classes of drugs (beta-blockers, angiotensin-converting enzyme inhibitors, and new oral anticoagulants). The choice of the most effective (from the standpoint of evidence-based medicine) is impossible if there are no direct comparisons in randomized controlled studies between drugs of the same class that have demonstrated their effectiveness separately. Analysis of observational studies (large databases, registers) to identify the most effective drug in a class cannot be used to solve the problem of the superiority of a drug within a class.

277-281 590

Currently, cardiovascular diseases play a leading role in the structure of morbidity. It is expected that by 2020 in developing countries cardiovascular diseases will take the leading position in the structure of mortality. Among the diseases of the cardiovascular system the leading position is occupied by coronary heart disease. One of the manifestations of coronary heart disease is acute coronary syndrome. In addition to endovascular treatment, dual antiplatelet therapy plays a key role in the treatment and prevention of acute coronary syndrome. Double antiplatelet therapy is a combination of acetylsalicylic acid and platelet P2Y12 receptor inhibitors. One of the first drugs from the group of P2Y12 receptor inhibitors is clopidogrel. It has been proven that the use of clopidogrel to date not always reduces the risk of development of thrombotic complications, of particular interest are the representatives of the "new" platelet P2Y12 receptor inhibitors. Such platelet P2Y12-receptor inhibitors include ticagrelor and prasugrel. The article considers in detail the issue of efficiency and safety of prasugrel use. The results of the studies allow to distinguish this drug as an effective inhibitor of P2Y12 platelet receptors in patients with acute coronary syndrome who have undergone percutaneous coronary intervention. Considering the pronounced antiplatelet effect of the drug, it should not be prescribed to patients with stroke and a history of transient ischemic attack. Prasugrel also should not be prescribed in a full dose to patients over 75 years old and patients weighing up to 60 kg. These studies showed that when the recommendations are followed, prasugrel demonstrates good results in reducing the frequency of cardiovascular events in patients with acute coronary syndrome and percutaneous coronary intervention. Separately, we can distinguish the effect of prasugrel on the development of stent thrombosis. So, in patients that underwent stenting, the use of prasugrel significantly reduced the frequency of confirmed stent thrombosis, which can also affect the development of undesirable cardiovascular events.


282-288 1275

Tactics for the management of patients with hypertriglyceridemia (HTG) is provided in the conclusion of the Advisory Board. It is demonstrated that HTG is quite prevalent in patients with excessive body weight and is an important component of residual risk. HTG creates additional conditions for the progression of atherosclerosis, and thus it is recommended to test triglyceride in patients with high, very high and extremely high cardiovascular risk. The indication for the pharmacological treatment to reduce the triglycerides concentration is their level more than 2.3 mmol/l. Statins are drugs of choice aimed to decrease the cardiovascular risk in patients with hypercholesterinemia and HTG. Fenofibrate is used to correct HTG; in case of its intolerance or if the triglyceride target level is not reached, ethyl esters of omega-3 polyunsaturated fatty acid can be used in the dosage of 2-4 g daily. In patients with triglyceride level higher than 5.6 mmol/l, fenofibrate is the main option of treatment.

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