Pitavastatin – a new inhibitor of the HMG-CoA reductase: peculiarities of clinical pharmacology and perspectives of its usage in treatment of cardiovascular diseases.

Cardiovascular mortality makes up 66.3 % of the total mortality in Ukraine. Myocardial infarction, stroke, atherosclerosis of peripheral arteries are the diseases caused by atherosclerosis and are prevalent in the mortality structure. One of the most effective means of successful prevention of cardiovascular disease are drugs that reduce the content of atherogenic lipids in the blood. Statins are the first line drugs for the treatment of patients with dyslipidemia and atherosclerosis in accordance with national and international guidelines. The article presents the features of the pharmacokinetics and pharmacodynamics, results of clinical trials and data on the efficacy and safety of a new inhibitor of the HMG-CoA reductase – pitavastatin (Livazo © (Recordati, Italy). Data from several multicenter randomized studies indicate that pitavastatin significantly reduces the level of cholesterol low-density lipoproteins and triglycerides, significantly increases the level of cholesterol high-density lipoproteins after 12 weeks of observation, and contributes to a significant regression of atherosclerotic plaques. It was shown that pitavastatin has a high level of safety and is well tolerated regardless of patients' age and racial origin. Pitavastatin is a new effective inhibitor of HMG -CoA reductase, which has been successfully used in many countries for the dyslipidemia treatment in patients with cardiovascular disease, diabetes, kidney diseases and other comorbid conditions

New concept of pathogenesis of impaired circulation in traumatic cervical spinal cord injury and its impact on disease severity: case series of four patients

Purpose: The purpose of this study is to justify a new concept of the pathogenesis of secondary changes in the cervical spinal cord, and its correlation with the depth of development of neurological disorders in spinal injury. Methods: Standard magnetic resonance imaging examination and angiography of the cervical and vertebral arteries of four patients were performed to diagnose the prevalence rate of ischemia and edema, and examine the spinal cord vasculature. Correlation of the data obtained with the neurological status was performed. Results: Collateral circulation is most apparent in the upper-cervical region, above the C4 vertebra. Following occlusion of the vertebral artery, the circulation above the C4 vertebra is performed by collaterals of the ascending cervical artery. With extensive damage to the spinal cord, the intensity of edema and ischemia can be regarded as the effect of damage to radicular medullary arteries, which are injured in the intervertebral foramen. Secondary changes of the spinal cord are most apparent by impaired circulation in the artery of cervical enlargement. Conclusions: Collateral circulation is a significant factor that limits the damage to the cervical spinal cord. Impaired circulation in the artery of cervical enlargement is significant in extension of perifocal ischemia. The appearance of early arteriovenous shunting in the region of a primary spinal cord injury (contusion focus) by angiography is pathognomonic. The data obtained open a perspective for the endovascular treatment of spinal cord injury

Діастолічна функція лівого шлуночка та рівень N-кінцевого промозкового натрійуретичного пептиду у хворих на фібриляцію передсердь

In our study 100 consecutive non-valvular permanent atrial fibrillation patients with NYHA I – III heart failure, 43 - 86 years old (65 men and 35 women) were examined. Control group consisted of 30 patients with arterial hypertension and coronary artery disease matched by age, sex with basic group. Relationship of NT-proBNP with echocardiographic parameters of left heart were studied. Transthoracic echocardiography with tissue doppler measurements were performed on echocardiograph “SONOS7500”. For left ventricular filling pressure assessment ratio Em/Ea was used due to its diagnostic value in atrial fibrillation (regardless of left ventricular ejection fraction). Mean left ventricular filling pressure was increased in patients with heart failure: in atrial fibrillation group and controls as well. In comparison with controls atrial fibrillation group was more likely to have higher both systolic and diastolic left atrial square and volume. According to Em/Ea in 95% of patients with non-valvular atrial fibrillation high left ventricular filling pressure was observed, this testifies to diastolic dysfunction. This parameter correlated well with left atrial square and volume during systole and diastole. Correlation between NT pro-BNP level and NYHA class of  heart failure, left ventricular filling pressure was determined in patients with atrial fibrillation. Tissue doppler echocardiography makes it possible to diagnose left ventricular diastolic dysfunction in atrial fibrillation patients.Обследовано 100 пациентов с постоянной формой фиб­рилляции предсердий неклапанного генеза и хронической недостаточностью І – ІІІ функционального класса в возрасте 43 – 86 лет, из них 65 мужчин и 35 – женщин. Контрольную группу составили 30 пациентов с ИБС и ГБ, сопоставимых по возрасту и полу с основной группой. Изучали уровень N-проМНП и его связь с эхокардиографическими показателями функции левых отделов сердца у данной категории больных. Эхокар­диографическое исследование и тканевая допплерография проводились на аппарате «SONOS 7500». Для оценки давления наполнения левого желудочка рассчитывали соотношение Em/Ea, которое полностью сохраняет свое диагностическое значение (независимо от фракции выброса левого желудочка) при фибрилляции предсердий. Средний показатель давления наполнения левого желудочка был увеличен у больных с хронической сердечной недостаточностью, как при постоянной фибрилляции предсердий, так и на фоне синусового ритма. Было установлено достоверное увеличение размеров левого предсердия, его площадей и объемов в систолу и ди­астолу в группе пациентов с фибрилляцией предсердий в сравнении с группой контроля. По данным показателя Еm/Eaу 95% пациентов с фибрилляцией предсердий неклаппаного генеза выявлено повышение давления наполнения левого желудочка, что свидетельствует о нарушении диастолической функции. Данный пока­затель достоверно коррелировал с объемами и площадями левого предсердия в систолу и диастолу. Уста­новлена достоверная связь между уровнем N-проМНП и функциональным классом сердечной недо­ста­точности, уровнем давления наполнений левого желудочка у пациентов с фибрилляцией предсердий. Использование тканевого допплеровского исследования позволяет диагностировать нарушение диасто­лической функции левого желудочка при фибрилляции предсердий.In our study 100 consecutive non-valvular permanent atrial fibrillation patients with NYHA I – III heart failure, 43 - 86 years old (65 men and 35 women) were examined. Control group consisted of 30 patients with arterial hypertension and coronary artery disease matched by age, sex with basic group. Relationship of NT-proBNP with echocardiographic parameters of left heart were studied. Transthoracic echocardiography with tissue doppler measurements were performed on echocardiograph “SONOS 7500”. For left ventricular filling pressure assessment ratio Em/Ea was used due to its diagnostic value in atrial fibrillation (regardless of left ventricular ejection fraction).Mean left ventricular filling pressure was increased in patients with heart failure: in atrial fibrillation group and controls as well. In comparison with controls atrial fibrillation group was more likely to have higher both systolic and diastolic left atrial square and volume. According to Em/Ea in 95% of patients with non-valvular atrial fibrillation high left ventricular filling pressure was observed, this testifies to diastolic dysfunction. This parameter correlated well with left atrial square and volume during systole and diastole. Correlation between NT pro-BNP level and NYHA class of  heart failure, left ventricular filling pressure was determined in patients with atrial fibrillation. Tissue doppler echocardiography makes it possible to diagnose left ventricular diastolic dysfunction in atrial fibrillation patients

Blood pressure-lowering effects of nifedipine/candesartan combinations in high-risk individuals: Subgroup analysis of the DISTINCT randomised trial

The DISTINCT study (reDefining Intervention with Studies Testing Innovative Nifedipine GITS - Candesartan Therapy) investigated the efficacy and safety of nifedipine GITS/candesartan cilexetil combinations vs respective monotherapies and placebo in patients with hypertension. This descriptive sub-analysis examined blood pressure (BP)-lowering effects in high-risk participants, including those with renal impairment (estimated glomerular filtration rate<90 ml min-1, n=422), type 2 diabetes mellitus (n=202), hypercholesterolaemia (n=206) and cardiovascular (CV) risk factors (n=971), as well as the impact of gender, age and body mass index (BMI). Participants with grade I/II hypertension were randomised to treatment with nifedipine GITS (N) 20, 30, 60 mg and/or candesartan cilexetil (C) 4, 8, 16, 32 mg or placebo for 8 weeks. Mean systolic BP and diastolic BP reductions after treatment in high-risk participants were greater, overall, with N/C combinations vs respective monotherapies or placebo, with indicators of a dose-response effect. Highest rates of BP control (ESH/ESC 2013 guideline criteria) were also achieved with highest doses of N/C combinations in each high-risk subgroup. The benefits of combination therapy vs monotherapy were additionally observed in patient subgroups categorised by gender, age or BMI. All high-risk participants reported fewer vasodilatory adverse events in the pooled N/C combination therapy than the N monotherapy group. In conclusion, consistent with the DISTINCT main study outcomes, high-risk participants showed greater reductions in BP and higher control rates with N/C combinations compared with respective monotherapies and lesser vasodilatory side-effects compared with N monotherapy

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation : Data From ROCKET AF

M. Kaste on työryhmän ROCKET AF Steering Comm jäsen.Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereasPeer reviewe

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

Structural and functional condition of the left ventricle and the arterial wall stiffness in patients with essential hypertension

Impact of the left ventricular hypertrophy (LVH) and increasing of the pulse wave velocity in aorta (PWV) at cardiovascular risk proved in various groups of patients. Aim. The aim of the study was to investigate the features of the myocardial structural and functional conditions and the arterial wall stiffness, as well as their relationship to male patients with essential hypertension (EH) I-II stage. Materials and methods. 53 male patients with essential hypertension stage I and II, aged 30–67 years were surveyed. All patients underwent clinical and laboratory examination in accordance with Ukrainian National Guidelines and ESH/ESC Guidelines for the management of arterial hypertension (2013). Echocardiography was performed in B- and M-modes. Elastic properties of the arterial wall were investigated with Arteriograph TensioMed (TensioClinic, Hungary). Conclusions. At the male patients with essential hypertension PWV was associated with increasing of LVM, LVMI, LVMI/h1,7 and LVMI/h2,7 by increased SWTat stage of the left ventricular hypertrophy formation. cSBP and cPP increase makes a significant contribution to the process of the heart remodeling in hypertensive patients with LVH. cPP increase contribute to LA size enlargement and LV systolic function reduce in patients with EH and LVH

Динаміка змін поверхневої цитоархітектоніки еритроцитів у хворих на цукровий діабет 2-го типу з артеріальною гіпертонією при корекції артеріального тиску лозартаном.

We have conducted a quantitative morphological evaluation of changes of erythrocyte surface cellular composition in patients with diabetes mellitus type 2 with arterial hypertension under correction of arterial blood pressure with losartan and with considering of glycaemic control level and microalbuminuria. It is shown that in the patients with diabetes mellitus in a compensation and subcompensation with arterial hypertension and microalbuminuria observedmoderate degree violations of erythrocyte surface cellular composition, as a result of this is a significant increase in the relative content of reversibly transformed cells.Insufficient glycaemic control in patients has been accompanied by considerable increase of reversible and irreversible transformed cells, especially in patients with microalbuminuria. The standard treatment for 1 year there has been a gradual increase in the degree of erythrocyte transformation. Inclusion of losartan in the treatment does not influence significantly the reversible transformation of erythrocytes, contributes to the normalization of the level of irreversibly transformed cells in patients with normalbuminuria and stabilizes them level with microalbuminuria, prevents the reduction of normal disk cells level.Проведена количественная морфологическая оценка динамики изменений поверхностной цитоархитектоники эритроцитов у больных сахарным диабетом 2-го типа с артериальной гипертонией при коррекции артериального давления лозартаном с учетом степени гликемического контроля и микроальбуминурии. Показано, что у больных сахарным диабетом в фазах компенсации и субкомпенсации с артериальной гипертонией и с микроальбуминурией отмечается умеренная степень нарушений поверхностной цитоархитектоники эритроцитов, что преимущественно проявляется в достоверном увеличении относительного содержания обратимо трансформированных клеток. При неудовлетворительном гликемическом контроле у больных наблюдается достоверное нарастание содержания обратимо и необратимо трансформированных эритроцитов, особенно у пациентов с микроальбуминурией. В условиях стандартного лечения на протяжении 1 года происходит постепенное нарастание степени трансформации эритроцитов. Включение в терапевтическую тактику лозартана не влияет существенно на обратимую трансформацию эритроцитов, способствует нормализации уровня необратимо трансформированных клеток у пациентов с нормальбуминурией и стабилизирует их уровень при наличии микроальбуминурии, предотвращает редукцию содержания нормальных дискоцитов.Проведено кількісну морфологічну оцінку динаміки змін поверхневої цитоархітектоніки еритроцитів у хворих на цукровий діабет 2-го типу з артеріальною гіпертонією при корекції артеріального тиску лозартаном з урахуванням ступеня глікемічного контролю та мікроальбумінурії. Показано, що у хворих на цукровий діабет 2-го типу у фазах компенсації і субкомпенсації з артеріальною гіпертонією і з мікроальбумінурією відзначається помірний ступінь порушень поверхневої цитоархітектоніки еритроцитів, що переважно виявляється у достовірному збільшенні відносного вмісту зворотно трансформованих клітин. При незадовільному глікемічному контролі у хворих спостерігається достовірне зростання вмісту зворотно і незворотно трансформованих еритроцитів, особливо у пацієнтів з мікроальбумінурією. За умов стандартного лікування впродовж 1 року відбувається поступове зростання ступеня трансформації еритроцитів. Залучення до терапевтичної тактики лозартану не впливає істотно на зворотну трансформацію еритроцитів, сприяє нормалізації рівня незворотно трансформованих клітин у пацієнтів з нормальбумінурією та стабілізує їх рівень за наявності мікроальбумінурії, попереджає редукцію вмісту нормальних дискоцитів