Background: Glucagon-like peptide 1 agonists differ in chemical structure, duration of action and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. Methods: We randomly assigned patients with type 2 diabetes and cardiovascular disease to the addition of once-weekly subcutaneous injection of albiglutide (30 mg to 50 mg) or matching placebo to standard care. We hypothesized that albiglutide would be noninferior to placebo for the primary outcome of first occurrence of cardiovascular death, myocardial infarction, or stroke. If noninferiority was confirmed by an upper limit of the 95% confidence interval for the hazard ratio of less than 1.30, closed-testing for superiority was prespecified. Findings: Overall, 9463 participants were followed for a median of 1.6 years. The primary composite outcome occurred in 338 of 4731 patients (7.1%; 4.6 events per 100 person-years) in the albiglutide group and in 428 of 4732 patients (9.0%; 5.9 events per 100 person-years) in the placebo group (hazard ratio, 0.78; 95% confidence interval [CI ], 0.68 to 0.90), indicating that albiglutide, was superior to placebo (P<0.0001 for noninferiority, P=0.0006 for superiority). The incidence of acute pancreatitis (albiglutide 10 patients and placebo 7 patients), pancreatic cancer (6 and 5), medullary thyroid carcinoma (0 and 0), and other serious adverse events did not differ significantly between the two groups. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. (Funded by GlaxoSmithKline; Harmony Outcomes ClinicalTrials.gov number, NCT02465515.) noninferiority; P = 0.06 for superiority). There seems to be variation in the results of existing trials with GLP-1 receptor agonists, which if correct, might reflect drug structure or duration of action, patients studied, duration of follow-up or other factors.

BackgroundAtrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all‐cause mortality may guide interventions.Methods and ResultsIn 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<0.0001) and age ≥75 years (hazard ratio 1.69, 95% CI 1.51–1.90, P<0.0001) were associated with higher all‐cause mortality. Multiple additional characteristics were independently associated with higher mortality, with decreasing creatinine clearance, chronic obstructive pulmonary disease, male sex, peripheral vascular disease, and diabetes being among the most strongly associated (model C‐index 0.677).ConclusionsIn a large population of patients anticoagulated for nonvalvular atrial fibrillation, ≈7 in 10 deaths were cardiovascular, whereas <1 in 10 deaths were caused by nonhemorrhagic stroke or systemic embolism. Optimal prevention and treatment of heart failure, renal impairment, chronic obstructive pulmonary disease, and diabetes may improve survival.Clinical Trial Registration URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00403767.

Objective. Assessment of the safety and efficacy of anticoagulant treatment in patients with nonvalvular atrial fibrillation (AF) in a multimorbidity setting.Materials and Methods. The cross-sectional study included 104 patients diagnosed with nonvalvular AF and followed in the medical facilities of Yekaterinburg. The subjects were interviewed, anthropometric measurements were made, and the risk of thromboembolic complications was evaluated using the CHA2DS2-VASc score. The Charlson multimorbidity index was calculated, and patients were divided into two groups: Group 1 with a low level of multimorbidity (not more than 5 points) and Group 2 with a high level of multimorbidity (6 points or more). The data are presented as a median and interquartile range (25%; 75%).Results.The study population included 40 males and 64 females. The median age was 71 (62.5; 80) years. The level of multimorbidity was estimated as 5 (3; 6) points. Group 1 included 64 patients, and Group 2 included 40 patients. Thirty-nine percent of the sample patients had a paroxysmal form of AF, 10% had a persistent form, and 51% had permanent AF. The group of patients with a high level of multimorbidity included more patients with permanent AF and fewer patients with paroxysmal AF as compared with a moderate level of multimorbidity (p<0.01). Anticoagulant treatment was indicated for 92 (88.5%) patients. It was administered to 70.7% of patients; 29.3% did not receive it. Among patients receiving anticoagulants, warfarin was administered to 18.5%, and new oral anticoagulants (NOACs) were administered to 81.5%. Complications were reported in 15.2% of anticoagulant treatment cases. Bleeding was reported in 21.7% of cases of warfarin administration and 12.5% of cases of NOAC treatment (p=0.32). The median number of risk factors for bleeding per patient was 5 (4; 5.5). The Charlson index and the total number of risk factors are significantly correlated (R=0.37, p<0.05).Conclusion. In real-world clinical practice in Ekaterinburg, Russia, 7 of 10 patients with AF for whom anticoagulant treatment was indicated actually received it; NOACs are prescribed four times more often than warfarin. With a higher level of multimorbidity, the risk of bleeding under the pressure of anticoagulant treatment increases; thus, NOACs should be preferred over warfarin for treatment of multimorbid patients.

Aim: to assess quality of life (QOL) of postmenopausal women with osteoporosis (OP) complicated by distant forearm fracture (DFF) in comparison with QOL of women with normal bone mineral density (BMD) and non-complicated OP. Methods: this case control study included 30 women with normal BMD, 30 persons with non-complicated OP and 30 patients with OP, complicated by DFF. SF-36 questionnaire was used to assess QOL.. Results: DFF was associated with restrictions in physical functioning in comparison to other groups (Р

Aim. To study the prevalence and features of cardiac arrhythmias (CA) in postmenopausal women, as well as to investigate the CA association with carbohydrate metabolism disturbances. Material and methods. This cross-sectional study included 210 postmenopausal women (median age 57 years; age range 54,0-61,0 years). Median menopause duration was 7,9 years (3,0-12,0 years). The examination included Holter ECG monitoring, clinical evaluation, measurement of blood pressure, body mass index, waist and hips circumference the levels of glucose, insulin, lipids, Mg, Ca, uric acid, brain natriuretic peptide, and thyrotropin. Results. CA were registered in 99,5% of the participants, including ischemia (17,1%), supraventricular extrasystolia (88,1%), ventricular extrasystolia (VE; 53,8%), high-grade VE (HGVE; 21,5%), SV tachycardia paroxysms (19%), atrial fibrillation (2,3%), V tachycardia paroxysms (1,4%), asystolic periods (0,9%), sino-atrial and atrioventricular blocks (9,1%), bundle branch blocks (3,3%), sinus tachycardia (50,9%), and sinus bradycardia (23,8%). In postmenopausal women with disturbed carbohydrate metabolism, CA prevalence was higher for VE (1,9 times), HGVE (2,4 times), and polytopic VE (2,5 times). VE prevalence was higher in women with abdominal obesity and chronic pancreatitis. In addition, CA odds were higher in postmenopausal women with coronary heart disease (CHD; 2,75 times), chronic heart failure (CHF; 2,6 times), and acute cardiovascular events such as myocardial infarction or stroke (3,3 times). Conclusion. CA and ischemia prevalence was high in postmenopausal women, 21,5% of whom had high potential risk of sudden death. Increased odds of ventricular arrhythmias among postmenopausal women were associated with carbohydrate metabolism disturbances, CHD, CHF.