Результаты длительного лечения бронходилататорами короткого действия больных хронической обструктивной болезнью легких (ХОБЛ) и ХОБЛ в сочетании с бронхиальной астмой

This study was designed to investigate long term treatment effects of short acting bronchodilators on respiratory symptoms, lung function, and the mean pulmonary artery pressure (mPAP) in patients with chronic obstructive pulmonary disease (COPD) and COPD combined with asthma (COPD + BA). The study involved 14 COPD patients and 16 COPD+BA patients, males and females (the average age, 60 yrs) with moderate to severe disease and the mPAP higher than 20 mm Hg. Clinical examination with scoring of cough, sputum, dyspnea, and lung auscultation signs; spirometry, ECG, echocardiography, chest X ray, and blood analysis were used. Clinical status and lung function were evaluated primarily and in 4, 12, and 24 wks; the mPAP was measured initially and in 12 and 24 wks. Before the study no one patient received persistent supporting therapy with bronchodilators, 15 COPD + BA patients and 7 COPD patients were given inhaled steroids. Persistent therapy of all the patients with Berodual 2 doses 4 times daily for 24 wks resulted in improvement in the clinical symptoms and lung function parameters, reduction in mPAP in both the groups but the results were better and they were reached faster in the patients with combined pathology. Thus, the regularly combined therapy with short acting β2 agonists and anticholinergics (Berodual) can be included in the algorithm of therapy of pulmonary hypertension in patients with COPD and COPD + BA.Целью настоящего исследования было изучение влияния бронхорасширяющих препаратов короткого действия на респираторную симптоматику, функцию внешнего дыхания и среднее давление в легочной артерии у больных хронической обструктивной болезнью легких (ХОБЛ) и ХОБЛ в сочетании с бронхиальной астмой (БА) при длительном применении. В исследование были включены 14 больных ХОБЛ и 16 больных ХОБЛ + БА (средний возраст — 60 лет, мужчины и женщины со средней и тяжелой стадиями заболевания и повышением среднего давления в легочной артерии > 20 мм рт. ст.) Применялись клиническое обследование больных, спирометрия, электрокардиография и эхокардиография, рентгенография легких, лабораторные исследования крови. Физикальное обследование и ФВД проводились исходно, через 4, 12 и 24 нед., среднее давление в легочной артерии определялось исходно, через 12 нед. и 24 нед. Клинические признаки (наличие и выраженность кашля, мокроты, одышки, аускультативная легочная симптоматика) оценивались в баллах. До включения в исследование больные не получали постоянной поддерживающей терапии бронходилататорами, 15 больных ХОБЛ + БА и 7 больных ХОБЛ получали ингаляционные кортикостероиды. Пациентам назначалась постоянная поддерживающая терапия Беродуалом по 2 дозы 4 раза в день в течение 24 нед. Результаты показали, что регулярная комбинированная бронходилатационная терапия Беродуалом больных ХОБЛ и ХОБЛ + БА приводит к уменьшению респираторной симптоматики, среднего давления в легочной артерии, улучшению показателей ФВД, однако при сочетанной патологии это происходит быстрее и в большей степени. Регулярная комбинированная бронходилатационная терапия β2 агонистами короткого действия и антихолинергическими препаратами короткого действия (Беродуалом) может быть включена в алгоритм лечения ЛГ у больных ХОБЛ и ХОБЛ + БА

Влияние бронходилататоров на легочную гипертензию у больных хронической обструктивной болезнью легких

Pulmonary hypertension and chronic cor pulmonale are the most important consequences of bronchial obstruction in COPD. Effects of typical bronchodilating therapy on the pulmonary artery haemodynamics are quite uncertain.The aim of this study was to search effects of long-term inhaled bronchodilating therapy on the pulmonary artery hypertension (PAH) in patient with COPD. The study involved 60 patients with 2 to 3 stage COPD and pulmonary artery pressure (PA P) higher than 20 mm Hg treated with Berodual 2 doses 4 times daily for 24 weeks. When having FEV1 less that 50 % of predicted values, patients received the drug via a nebulizer. The main COPD symptoms (cough, sputum, dyspnoea, wheesing) were scored. We also used spirometry, chest X- ray, ECG and Doppler echocardiography.On the 24-week therapy the main symptoms reduced from 7.6 ± 0.4 до 1.6 ± 0.2 numbers (p < 0.05), the PAH dropped from 32.3 ± 0.8 до 23.2 ± 1.2 mm Hg (p < 0.05). The ECG and the chest X-ray examination appeared to be not quite valuable to detect PAH. Therefore, the Doppler echocardiography is thought to be used to diagnose PAH in COPD. As far as the long-term bronchodilating therapy resulted in the PAP decrease, it should be included to an algorithm of managing COPD patients with PAH.Одним из важнейших следствий бронхиальной обструкции при хронической обструктивной болезни легких (ХОБЛ) является формирование легочной гипертензии (ЛГ) и хронического легочного сердца. Недостаточно изученным остается вопрос о влиянии классической бронходилатирующей терапии на гемодинамику в бассейне легочной артерии.Целью настоящего исследования явилось изучение влияния длительного применения ингаляционных бронхорасширяющих средств на ЛГ у больных ХОБЛ. Исследованы 60 больных ХОБЛ 2-3-й стадий с ЛГ (более 20 мм рт. ст.) на фоне постоянной терапии Беродуалом по 2 дозы 4 раза в день в течение 24 нед. Больные с ОФВ1 менее 50 % от должных величин ингалировали препарат через небулайзер. Оценивали клиническое состояние пациентов с использованием балльной оценки выраженности кашля, мокроты, одышки, аускультативных изменений в легких, проводили спирометрию, рентгенографию легких, ЭКГ, допплеровскую эхокардиографию. На фоне терапии в течение 24 нед. произошло уменьшение основных симптомов заболевания с 7,6 ± 0,4 до 1,6 ± 0,2 баллов (р < 0,05), снижение среднего давления в легочной артерии (Рла) с 32,3 ± 0,8 до 23,2 ± 1,2 мм рт. ст. (р < 0,05). Показана недостаточная диагностическая значимость Э К Г и рентгенографии легких в выявлении ЛГ у больных ХОБЛ.Таким образом, для диагностики ЛГ у больных ХОБЛ должна применяться допплеровская эхокардиография. Длительная бронходилатационная терапия приводит к снижению Рла, вследствие чего она может быть включена в алгоритм лечения ЛГ у больных ХОБЛ

Effect of SGLT2 inhibitors on stroke and atrial fibrillation in diabetic kidney disease: Results from the CREDENCE trial and meta-analysis

BACKGROUND AND PURPOSE: Chronic kidney disease with reduced estimated glomerular filtration rate or elevated albuminuria increases risk for ischemic and hemorrhagic stroke. This study assessed the effects of sodium glucose cotransporter 2 inhibitors (SGLT2i) on stroke and atrial fibrillation/flutter (AF/AFL) from CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation) and a meta-Analysis of large cardiovascular outcome trials (CVOTs) of SGLT2i in type 2 diabetes mellitus. METHODS: CREDENCE randomized 4401 participants with type 2 diabetes mellitus and chronic kidney disease to canagliflozin or placebo. Post hoc, we estimated effects on fatal or nonfatal stroke, stroke subtypes, and intermediate markers of stroke risk including AF/AFL. Stroke and AF/AFL data from 3 other completed large CVOTs and CREDENCE were pooled using random-effects meta-Analysis. RESULTS: In CREDENCE, 142 participants experienced a stroke during follow-up (10.9/1000 patient-years with canagliflozin, 14.2/1000 patient-years with placebo; hazard ratio [HR], 0.77 [95% CI, 0.55-1.08]). Effects by stroke subtypes were: ischemic (HR, 0.88 [95% CI, 0.61-1.28]; n=111), hemorrhagic (HR, 0.50 [95% CI, 0.19-1.32]; n=18), and undetermined (HR, 0.54 [95% CI, 0.20-1.46]; n=17). There was no clear effect on AF/AFL (HR, 0.76 [95% CI, 0.53-1.10]; n=115). The overall effects in the 4 CVOTs combined were: Total stroke (HRpooled, 0.96 [95% CI, 0.82-1.12]), ischemic stroke (HRpooled, 1.01 [95% CI, 0.89-1.14]), hemorrhagic stroke (HRpooled, 0.50 [95% CI, 0.30-0.83]), undetermined stroke (HRpooled, 0.86 [95% CI, 0.49-1.51]), and AF/AFL (HRpooled, 0.81 [95% CI, 0.71-0.93]). There was evidence that SGLT2i effects on total stroke varied by baseline estimated glomerular filtration rate (P=0.01), with protection in the lowest estimated glomerular filtration rate (45 mL/min/1.73 m2]) subgroup (HRpooled, 0.50 [95% CI, 0.31-0.79]). CONCLUSIONS: Although we found no clear effect of SGLT2i on total stroke in CREDENCE or across trials combined, there was some evidence of benefit in preventing hemorrhagic stroke and AF/AFL, as well as total stroke for those with lowest estimated glomerular filtration rate. Future research should focus on confirming these data and exploring potential mechanisms

Canagliflozin and Renal Outcomes in Type 2 Diabetes and Nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to 300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m 2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

RENAISSANCE OF ARTERIAL HYPERTENSION MONOTHERAPY – THE POSITION OF THIAZIDE DIURETICS

The importance of the optimal choice of antihypertensive treatment strategy is currently widely recognised. The evidence obtained over the last five years justifies the revision of the traditional approach towards the tactics of mono- and combination antihypertensive therapy. It is essential to ensure that the patient-centred tactics of mono- and combination therapy choice is based on the detailed analysis of the clinical status

CHRONIC COR PULMONALE

Chronic cor pulmonale

Optimizing antihypertensive therapy in postmenopausal women with metabolic syndrome

Aim. To compare the effects of antihypertensive medications (AHM) on central hemodynamics, metabolic profile, insulin resistance (IR), oxidant and antioxidant systems in postmenopausal patients with metabolic disturbances and Stage I-II arterial hypertension (AH).Material and methods. The study included 47 postmenopausal women with metabolic syndrome (MS) and Stage I-II AH. Group I (n=31) received an ACE inhibitor spirapril (6 mg/d) for 6 months. Group II (n=16) received various AHM administered as a part of ambulatory therapy. At baseline and after 6 months of the treatment, all participants underwent 24-hour blood pressure monitoring (BPM), echocardiography, lipid profile (LP) and IR index HOMA assessment, oral glucose tolerance test, double energy X-ray absorptiometry with general and regional analysis of body composition, as well as the measurement of lipid acylhydroperoxide levels and erythrocyte superoxide dismutase activity.Results. In both groups, target BP levels were achieved. In Group I, left ventricular myocardial mass index (LVMMI) significantly decreased (р&lt;0,001). In Group II, only a tendency towards LVMMI reduction was observed (р=0,062). Body mass index and visceral fat tissue percentage increased in both groups. Spirapril therapy was associated with increased levels of high-density lipoprotein cholesterol, HDL-CH (p=0,001), and decreased concentration of triglycerides (р=0,03). In Group II, no LP dynamics was observed, while IR increased. Spirapril therapy was associated with IR index (HOMA) normalisation (р&lt;0,001) and improved oxidant-antioxidant bal¬ance (р&lt;0,001), with no similar changes in Group II.Conclusion. Spirapril demonstrated beneficial effects on carbohydrate and lipid metabolism, IR and oxidant-antioxidant parameters, as well as cardioprotective activity

ANTIANGINAL AND ANTI2ISCHEMIC EFFECTIVENESS AND TOLERABILITY OF OXICARDIN IN PATIENTS WITH STABLE ANGINA OF I-III FUNCTIONAL CLASSES: RESULTS OF A RUSSIAN MULTICENTER RUSSIA

Antianginal and anti2ischemic effectiveness and tolerability of oxicardin in patients with stable angina of I-III functional classes: results of a Russian multicenter Russia

Нарушения ритма сердца у больных хроническими обструктивными болезнями легких

To evaluate frequency, natural history and peculiarities of cardiac arrhythmia in patients with chronic obstructive pulmonary diseases (COPD) under occurring and progressing of chronic cor pulmonale (CCP) 226 patients were examined using daily ECC Holter monitoring, Doppler echocardiography, lung function tests, the blood gas analysis. The data obtained demonstrate a prevalence of supraventricular arrhythmia in COPD patients and suppose that the right heart hypertrophy and/or dilation and the right ventricular diastolic dysfunction greatly contribute to the natural history of supraventricular arrhythmia when CCP developing. Ventricular extrasystole seems to be caused by the left ventricular myocardial metabolic disorders due to the chronic hypoxia.С целью выявления частоты, генеза и особенностей нарушений ритма сердца у больных хроническими обструктивными болезнями легких (ХОБЛ) по мере формирования и прогрессирования хронического легочного сердца (ХЛС) обследовано 226 пациентов с ХОБЛ. Всем больным проведено суточное мониторирование ЭК Г по Холтеру, эходопплерокардиография, функция внешнего дыхания, исследовался газовый состав крови. Наши данные свидетельствуют о преобладании наджелудочковых аритмий у больных ХОБЛ и позволяют предположить, что при формировании ХЛС в генезе суправентрикулярных аритмий на первый план выступают гипертрофия и/или дилатация правых отделов сердца и нарушение диастолической функции правого желудочка, а при Ж ЭС ведущая роль принадлежит метаболическим нарушениям миокарда левого желудочка вследствие хронической гипоксии

Combined antihypertensive therapy in patients with chronic obstructive pulmonary disease

Aim. To investigate endothelium-regulating and antioxidant effects of trandolapril and verapamil SR combination (Tarka) in patients with arterial hypertension (AH) and chronic obstructive pulmonary disease (COPD).Material and methods. In total, 42 COPD and AH patients, aged 48-70 years, were examined. All participants received continuous basis COPD treatment and 16-week Tarka therapy. At baseline and at the end of the study, lung function, systemic inflammation, oxidative stress and antioxidant potential parameters were measured.Results. All patients achieved office-measured target blood pressure (BP) levels. Bronchial conductivity increase was explained by therapy-associated improvement in pulmonary hemodynamics. The medication was safe and well-tolerated by patients with COPD and AH. Decrease in C-reactive protein levels, possibly explaining antiinflammatory medication effect, pointed to the suppression of endothelium-damaging influences. The treatment was also associated with decreased lipid peroxidation, reduced serum levels of acylhydroperoxides, and increased concentration and activity of antioxidant enzymes.Conclusion. AH and COPD therapy should include antihypertensive agents with pleiotropic effects, specifi- cally, suppressing systemic inflammation, correcting endothelial function, and enhancing antioxidant potential. These characteristics could act as additional criteria of AH treatment effectiveness in patients with combined cardiovascular and respiratory pathology