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.

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Patients with combined coronary heart disease and diabetes mellitus make up a growing segment of the population and require a com¬prehensive treatment approach. Patients with concurrent diabetes mellitus and coronary heart disease have a worse projection. Under these conditions, the incidence of recurrent myocardial infarction, early disability due to complications, and the risk of coronary death are increased. Therefore, the priority task is to find ways to optimize drug treatment of this category of patients, taking into account the impact of drugs on the pathogenetic links of coronary heart disease progression and the development of cardiovascular complications. One hundred twelve people were examined in the research. The patients had type 2 diabetes with a history of non-Q-myocardial infarction receiving oral antidiabetic therapy and basic therapy, including an ACE inhibitor, a β-blocker, a statin, and an antiplatelet agent. Analysis of the investigated parameters in the leading group after receiving alpha-lipoic acid for 4 months showed a significant decrease in the concentration of C-Reactive Protein, IL-6 and TNF-α. According to the results of our research, taking alpha-lipoic acid for 4 months in patients with type 2 diabetes who underwent non-Q-myocardial infarction reduced the activity of systemic inflammation and did not significantly affect the content of anti-inflammatory IL-10 in patients. In light of the above, it is of interest to administer alpha-lipoic acid to these patients, considering the positive effects of the agent such as antioxidant properties, vasorelaxation, positive metabolic profile, as well as an anti-inflammatory potential.

Statins are the integral medications for the management of patients with acute coronary syndrome including unstable angina (UA) with multiple pleiotropic effects. However, the influence of statins on the coagulation system is controversial. Our study aimed to explore the effects of atorvastatin and rosuvastatin in high doses on some coagulation parameters (prothrombin pool (PP) and soluble fibrin-monomer complexes (SFMC) concentration) after a 7-days follow-up period in patients with UA. We recruited 50 patients aged 55 to 70 years with progressive UA. Standard therapy according to ESC guidelines 2020 was recommended for all patients. Before treatment onset, they were divided into 2 groups: group A – 26 patients were prescribed atorvastatin, group R – 24 patients with rosuvastatin treatment. The blood samples to analyze the concentration of PP and SFMC were collected twice – before the treatment onset and 7 days after. We revealed significant decrease in PP concentration (p=0,02) and increase in SFMC concentration (p=0,01) in group A patients while there were no significant changes of investigated parameters (p=0,94, p=0,57 respectively) in group R. Additionally, we have noted significant negative correlation between baseline PP concentration and direction of PP changes (r=-0,803, p<0,001) as well as PP changes direction and SFMC concentration after treatment (r=-0,655, p<0,001). Thus, we may consider that atorvastatin and rosuvastatin are characterized by different influences on coagulation in patients with progressive UA with standard basic treatment. The rebound coagulation system activation after anticoagulant discontinuation is more pronounced in UA patients against a background of atorvastatin treatment in comparison with rosuvastatin.

Aim: To investigate the serotonin and von Willebrand factor (vWF) concentrations among unstable angina (UA) patients without and with progression toward myocardial infarction (outcome) and to assess the utility of both as prognostic markers of UA complications. Materials and methods: In observational cohort study, we recruited 103 patients with ischemic heart disease (the median age 65.0 (59.0-69.0) years, 45 females (43.7%)). After full set of investigations including high sensitive Troponin I test and 28-day follow-up period, we defined three groups: Group 1 - stable angina patients (n=22) as control, Group 2 - UA patients without outcome (n=71), Group 3 - UA patients with outcome (n=10). We analyzed the blood plasma serotonin content by the ion-exchange chromatography with measurement of serotonin on fluorescence spectrophotometer. VWF concentration was determined by ELISA. We compared the concentrations of observed parameters among the groups with the Kruskal-Wallis test (with post-hoc Mann-Whitney test with Bonferroni-Holm correction). We assessed binary logistic models, receiver operating characteristic curves, calculated sensitivity (Se), specificity (Sp), and positive likelihood ratio (LR+) for each indicator. Results: We registered elevation in serotonin concentration and decline in vWF concentration in Group 3 in comparison with Group 2 (22.670 (20.687-24.927) μg/ml vs 11.980 (8.120-15.000) μg/ml, p< 0.001, and 0.117 (0.109-0.120) rel.units/ml vs 0.134 (0.127-0.143) rel.units/ml, p < 0.001) and Group 1 (12.340 (10.052-13.619) μg/ml, p < 0.001, and 0.137 (0.127-0.156) rel.units/ml, p < 0.001), respectively. No significant differences in serotonin and vWF concentrations between Group 1 and Group 2 were detected (p=0.81 and p=0.36, respectively). The probability of outcome increased significantly (by 60.7% and 59.7%, LR+ 19.0 [6.0, 60.0] and 18.0 [3.9, 80.0]) if serotonin concentration was above 21.575 μg/ml (Se=80.0%, Sp=95.8%, AUC=0.975) and vWF concentration was below 0.114 rel.units/ml (Se=50.0%, Sp=97.2%, AUC=0.973), respectively. Conclusions: Serotonin and vWF as biomarkers are demonstrated promising results for rule-in the patients with risk of short-term UA progression toward myocardial infarction.

Unstable angina is classified into new-onset, progressive, and angina at rest. Though hemostasis plays a crucial role in the pathogenesis of coronary artery disease, including unstable angina, limited data exist regarding peculiarities of fibrinolytic parameters in the above-mentioned types of unstable angina. Our study aims to investigate if there is a difference in the fibrinolytic state between the groups of patients with new-onset, progressive unstable angina in comparison with stable angina patients depending on medical history data, electrocardiographic and hemodynamic features. In our cross-sectional study, we recruited 93 coronary artery disease patients (mean age 62.32 (6.94) years, 41 males (44.1%)). They were divided into 3 groups: stable angina patients (n=22) (control), new-onset unstable angina patients (n=21), and progressive unstable angina patients (n=50). The groups were comparable by baseline characteristics. Blood samples were obtained before treatment onset. The concentrations of tissue plasminogen activator and inhibitor of plasminogen activator (type 1) were measured by the ELISA method. We registered 14 points at the admission department, particularly age, sex, body mass index, smoking, presence of the family history of cardiovascular disorders, ST-segment depression, T-wave variability, arrhythmias, left bundle branch blockage, heart rate, systolic and diastolic blood pressure, Sokolov-Lyon voltage criteria, and unstable angina type (new-onset or progressive). After comparison of fibrinolytic parameters’ concentrations among groups under investigation, we defined the main independent predictors among observed 14 parameters to create optimal regression models for assessment of fibrinolytic parameters concentrations. The groups under investigation differ significantly in concentration of tissue plasminogen activator (P<0.001) and inhibitor of plasminogen activator (type 1) (P<0.001). The tissue plasminogen activator concentration correlated significantly with ST depression (r=0.344, P=0.001), T wave variability (r=-0.233, P=0.02), systolic blood pressure (r=-0.675, P<0.001), diastolic blood pressure (r=-0.655, P<0.001), heart rate (r=-0.568, P<0.001) and clinical unstable angina subgroups (r=-0.706, P<0.001) as well as plasminogen activator inhibitor (type 1) concentration associated with age (r=-0.560, P<0.001), body mass index (r=-0.249, P=0.049), ST-segment depression (r=0.542, P<0.001), arrhythmia (r=0.210, P=0.03), systolic blood pressure (r=0.310, P=0.04), and clinical unstable angina subgroups (r=-0.406, P<0.001). An optimal regression models for tissue plasminogen activator and its inhibitor assessment included systolic blood pressure, heart rate, unstable angina subgroup (R2adj. = 65.0%, P<0.001) and systolic blood pressure, unstable angina subgroup (R2adj. = 42.7%, P<0.001), respectively. Thus, fibrinolytic state among unstable angina clinical types differs significantly independently on observed baseline clinical, electrocardiographic and hemodynamic parameters. This finding confirms the utility of Braunwald unstable angina classification.

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equal to 3) of 53.5%. The mean creatinine clearance value was 118.48 ml/min and the mean follow-up of these patients was 13.57 months. Results: : It has not been reported any case of Stroke, Systemic Embolism, or Major Bleeding (according to the criteria of the ISTH) during the follow-up time of the patients treated, both in the main group and in the subpopulation of patients with creatinine clearance above 95 ml/min. Only 3% of patients (17) had complications with Edoxaban, of which 12 had discontinued treatment for this cause. No case of severe or clinically relevant major bleeding has been reported according to the ISTH criteria. During the time of follow-up, twelve cases of death occurred from their base disease or from other causes, but in no case related to Edoxaban. Summary/Conclusion: This is a good sample of 552 patients and more than with a mean of 13 months of follow-up. In the analyzed subpopulation of patients with creatinine clearance greater than 95 ml/min, the good results of Edoxaban are confirmed since they have not presented any stroke recurrence or systemic embolism or major or clinically relevant hemorrhage according to the ISTH criteria. Due to the sample of 127 patients, more studies will be needed to confirm this assertion.