SGLT2 inhibitors and kidneys: mechanisms and main effects in diabetes mellitus patients

Type 2 diabetes mellitus (T2DM) is the cause of the development of diabetic nephropathy — a complication that determines the high degree of disability and mortality of such patients. Until recently, approaches to normalizing glucose levels did not have a significant possibility of influencing the outcome of kidney damage in diabetes. Type 2 sodium glucose cotransporter inhibitors (SGLT2) are a new class of glucose-lowering drugs that improve glycemic control due to an insulin-independent mechanism of action associated with increased urinary glucose excretion. The review provides an analysis of the results of studies on the assessment of nephroprotective actions — one of the pleiotropic actions of this drugs group. These materials show the properties of SGLT2 inhibitors to reduce the risk of developing and the progression of albuminuria, to save glomerular filtration rate, to reduce the frequency of end-stage renal disease and the need for renal replacement therapy in patients with T2DM. The article gives and analyzes the currently existing hypotheses of the mechanism of action of these glucose-lowering drugs. The risk of the most common renal complications with the use of SGLT2 inhibitors is considered. The practical aspects of the use of SGLT2 inhibitors in modern algorithms for the care of patients with T2DM are indicated, as well as the prospects for new randomized clinical trials

Decrease of cardiovascular risk in patients with type 2 diabetes: review of the common strategies and clinical studies

Military Medical Academy of S.M. Kirov, Saint-Petersburg, Russia Recent clinical trials about the cardiovascular safety of empagliflozin and liraglutide demonstrated a convincing lowering effect on mortality from cardiovascular causes among the patients with type 2 diabetes. These findings resulted in many questions about why this phenomenon was seen in two drugs with widely different mechanisms of functioning. It is important to note that the glucose-lowering effect was moderate, although a feature seen in both empagliflozin and liraglutide was their ability to increase insulin sensitivity. In many fundamental studies, this feature was associated with a reduction of cardiovascular risks. Insulin resistance, which has always been a pathophysiological base for the development of cardiovascular disease in patients with type 2 diabetes, is a topic for this report. Different methods to manage insulin resistance, including lifestyle changes, drug treatment and metabolic surgery, are discussed. Furthermore, the most common features of glucose-lowering drugs are analysed, including protective effects for cardiovascular outcomes in patients with type 2 diabetes presented in randomised clinical trials. Studies include the United Kingdom Prospective Diabetes Study (UKPDS), PROspective pioglitAzone Clinical Trial In macroVascular Events (PROactive), Insulin Resistance Intervention After Stroke (IRIS), Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) and the Empagliflozin Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME). The current study shows that the potential to reduce the risk of cardiovascular disease is determined not only by effective lowering of glucose but also by the ability to lower insulin resistance, which causes a paradigm shift in the management of type 2 diabetes

Нарушения функции внешнего дыхания при различных формах легочной патологии

The most common lung function abnormalities in patients with respiratory diseases have been reviewed in the article. Ventilation disorders with change in the lung volumes, bronchial obstruction and hypoxemia are typical for patients with pneumonia. Lung compliance reduction, inconsistency of ventilation, and ventilation perfusion mismatch could be found in chronic non-obstructive bronchitis. Chronic obstructive pulmonary disease is associated with bronchial obstruction which is defined as decreased forced expiratory volume for 1 sec (FEV1) and forced expiratory flows at different levels of forced vital capacity (FVC) and increased airway resistance. Asthma is associated with reversible change in expiratory flows, such as FEV1 and peak expiratory flow, due to bronchial hyperresponsiveness. Residual volume (RV) could increase in patients with acute asthma attack. Emphysema is characterized by changes in lung volumes, primarily due to increased RV; lung diffusing capacity (DLCO) could decrease and the lung perfusion could change. Mixed (obstructive and restrictive) lung ventilation disorders could be diagnosed in patients with chronic purulent lung diseases. Patients with disseminated lung lesions could demonstrate decreased lung compliance, reduced lung volumes, decreased DLCO and hypoxemia without hypercapnia.Представлены наиболее типичные нарушения функции внешнего дыхания (ФВД) у больных пульмонологического профиля. При пневмонии нарушается вентиляция, страдают легочные объемы, имеют место нарушения бронхиальной проходимости, развивается артериальная гипоксемия. При хроническом необструктивном бронхите выявляются некоторое снижение растяжимости легких, нарушения равномерности вентиляции, признаки нарушения вентиляционно-перфузионных отношений. У пациентов с хронической обструктивной болезнью легких (ХОБЛ) бронхиальная обструкция имеет генерализованный характер, что выражается в снижении объема форсированного выдоха за 1-ю секунду (ОФВ1), уменьшении объемной скорости потока на различных уровнях форсированной жизненной емкости легких и увеличении бронхиального сопротивления. Существенные изменения претерпевают легочные объемы, особенно остаточный объем (ООЛ) и общая емкость (ОЕЛ) легких. При бронхиальной астме (БА) регистрируется преходящее лабильное изменение скоростных параметров спирометрии (ОФВ1, пиковая скорость выдоха), обусловленное бронхиальной гиперреактивностью. В период обострения БА также регистрируется увеличение ООЛ. У лиц с эмфиземой легких нарушения ФВД проявляются изменением структуры ОЕЛ за счет увеличения ООЛ. Снижается диффузионная способность легких (DLCO), отмечаются нарушения перфузии. У пациентов с хроническими нагноительными заболеваниями легких отмечаются нарушения вентиляции по смешанному типу (рестриктивные и обструктивные). Для диссеминированных заболеваний легких характерно уменьшение растяжимости легких и легочных объемов, снижение DLCO, развитие артериальной гипоксемии (без гиперкапнии)

Apixaban versus warfarin in patients with atrial fibrillation

BACKGROUND: Vitamin K antagonists are highly effective in preventing stroke in patients with atrial fibrillation but have several limitations. Apixaban is a novel oral direct factor Xa inhibitor that has been shown to reduce the risk of stroke in a similar population in comparison with aspirin. METHODS: In this randomized, double-blind trial, we compared apixaban (at a dose of 5 mg twice daily) with warfarin (target international normalized ratio, 2.0 to 3.0) in 18,201 patients with atrial fibrillation and at least one additional risk factor for stroke. The primary outcome was ischemic or hemorrhagic stroke or systemic embolism. The trial was designed to test for noninferiority, with key secondary objectives of testing for superiority with respect to the primary outcome and to the rates of major bleeding and death from any cause. RESULTS: The median duration of follow-up was 1.8 years. The rate of the primary outcome was 1.27% per year in the apixaban group, as compared with 1.60% per year in the warfarin group (hazard ratio with apixaban, 0.79; 95% confidence interval [CI], 0.66 to 0.95; P<0.001 for noninferiority; P = 0.01 for superiority). The rate of major bleeding was 2.13% per year in the apixaban group, as compared with 3.09% per year in the warfarin group (hazard ratio, 0.69; 95% CI, 0.60 to 0.80; P<0.001), and the rates of death from any cause were 3.52% and 3.94%, respectively (hazard ratio, 0.89; 95% CI, 0.80 to 0.99; P = 0.047). The rate of hemorrhagic stroke was 0.24% per year in the apixaban group, as compared with 0.47% per year in the warfarin group (hazard ratio, 0.51; 95% CI, 0.35 to 0.75; P<0.001), and the rate of ischemic or uncertain type of stroke was 0.97% per year in the apixaban group and 1.05% per year in the warfarin group (hazard ratio, 0.92; 95% CI, 0.74 to 1.13; P = 0.42). CONCLUSIONS: In patients with atrial fibrillation, apixaban was superior to warfarin in preventing stroke or systemic embolism, caused less bleeding, and resulted in lower mortality. Copyright © 2011 Massachusetts Medical Society. All rights reserved

Apixaban compared with warfarin in patients with atrial fibrillation and previous stroke or transient ischaemic attack: A subgroup analysis of the ARISTOTLE trial

Background: In the ARISTOTLE trial, the rate of stroke or systemic embolism was reduced by apixaban compared with warfarin in patients with atrial fibrillation (AF). Patients with AF and previous stroke or transient ischaemic attack (TIA) have a high risk of stroke. We therefore aimed to assess the efficacy and safety of apixaban compared with warfarin in prespecified subgroups of patients with and without previous stroke or TIA. Methods: Between Dec 19, 2006, and April 2, 2010, patients were enrolled in the ARISTOTLE trial at 1034 clinical sites in 39 countries. 18 201 patients with AF or atrial flutter were randomly assigned to receive apixaban 5 mg twice daily or warfarin (target international normalised ratio 2·0-3·0). The median duration of follow-up was 1·8 years (IQR 1·4-2·3). The primary efficacy outcome was stroke or systemic embolism, analysed by intention to treat. The primary safety outcome was major bleeding in the on-treatment population. All participants, investigators, and sponsors were masked to treatment assignments. In this subgroup analysis, we estimated event rates and used Cox models to compare outcomes in patients with and without previous stroke or TIA. The ARISTOTLE trial is registered with ClinicalTrials.gov, number NTC00412984. Findings: Of the trial population, 3436 (19%) had a previous stroke or TIA. In the subgroup of patients with previous stroke or TIA, the rate of stroke or systemic embolism was 2·46 per 100 patient-years of follow-up in the apixaban group and 3·24 in the warfarin group (hazard ratio [HR] 0·76, 95% CI 0·56 to 1·03); in the subgroup of patients without previous stroke or TIA, the rate of stroke or systemic embolism was 1·01 per 100 patient-years of follow-up with apixaban and 1·23 with warfarin (HR 0·82, 95% CI 0·65 to 1·03; p for interaction=0·71). The absolute reduction in the rate of stroke and systemic embolism with apixaban versus warfarin was 0·77 per 100 patient-years of follow-up (95% CI -0·08 to 1·63) in patients with and 0·22 (-0·03 to 0·47) in those without previous stroke or TIA. The difference in major bleeding with apixaban compared with warfarin was 1·07 per 100 patient-years (95% CI 0·09-2·04) in patients with and 0·93 (0·54-1·32) in those without previous stroke or TIA. Interpretation: The effects of apixaban versus warfarin were consistent in patients with AF with and without previous stroke or TIA. Owing to the higher risk of these outcomes in patients with previous stroke or TIA, the absolute benefits of apixaban might be greater in this population. Funding: Bristol-Myers Squibb and Pfizer. © 2012 Elsevier Ltd

Alirocumab and cardiovascular outcomes after acute coronary syndrome

BACKGROUN