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Aim: To evaluate the prognostic value of GDF-15 in relation the development of bleeding and events in stable CAD patients, receiving combined antithrombotic therapy., Materials and Methods: The data was obtained from the prospective registry REGATA, 343 CAD patients (249 males), median age 68 [IQR 62; 75] years) were enrolled. Patients with sinus rhythm and concomitant PAD received acetylsalicylic acid in combination with rivaroxaban 2.5 mg bid (31.8%) or clopidogrel (24.8%). Other 43.4% with concomitant atrial fibrillation (AF) received direct oral anticoagulants in combination with antiplatelet therapy after elective percutaneous coronary interventions. Median follow-up was 12 months [ IQR 9.0 ; 18.0]. The safety end point was major and clinically relevant bleedings (type 2-5) according to the BARC classification. Plasma samples for GDF-15 identification were taken at the inclusion and analyzed using ELISA assay., Results: Frequency of BARC 2-5 bleedings was 16% (BARC 2 - 46; BARC 3 - 9; BARC 4-5 - 0), median GDF-15 level was 1185.0 pg/ml [850.0; 1680.0]. In patients with AF and concomitant MFA, the level of GDF-15 was significantly higher than in the subgroups of patients with only AF or MFA ( p =0.0022). According to the quintile analysis, GDF-15 values in the top three quintiles of distribution (cut-off value >943 pg/ml) were associated with higher frequency of bleeding events: 23.2% versus 5.1%; p =0.0001. The multivariable logistic regression model demonstrated that bleeding events were independently associated with GDF-15 level>943 pg/ml (OR 2.65, 95% CI 1.11-6.30; p =0.0275), AF (OR 2.61, 95% CI 1.41-4.83; p =0.0023) and chronic kidney disease (OR 1.92, 95% CI 1.03-3.60; p =0.0401). Clinical factors determining the risk of bleeding events also determined a GDF-15 elevation., Conclusion: Assessment of GDF-15 level may improve bleeding risk stratification in CAD patients with concomitant AF and/or PAD receiving combined antithrombotic therapy.

Background: It is necessary to strive to resume anticoagulants for patients with atrial fibrillation who have a high risk of thrombosis after the development of large bleeding. Due to the fact that death in these patients is caused not by a recurrence of fatal bleeding, but by the development of stroke in case of refusal of anticoagulant therapy., Aim: To evaluate the effect of the resumption of anticoagulant therapy on the risk of recurrence of major bleeding, thrombosis and death in patients with atrial fibrillation who have suffered major bleeding., Materials and Methods: To evaluate the frequency of bleeding, thrombosis and death in patients with atrial fibrillation after major bleeding according to prospective follow-up data for one year., Results: The recurrence rate of major bleeding after the resumption of therapy was 21.7% per year. The frequency of fatal bleeding was 2.2%. In the anticoagulant withdrawal group, the incidence of thrombotic complications (ischemic stroke and myocardial infarction) was significantly higher compared to patients who resumed therapy. The frequency of death from all causes was significantly higher in the group of patients who did not resume anticoagulant therapy. Half of the deaths were due to cardiovascular causes. The presence of more than 5 points of the Charlson Comorbidity Index was a predictor of the development of the sum of all adverse events., Conclusion: The resumption of anticoagulant therapy after the development of major bleeding in patients with atrial fibrillation reduces the risk of thrombosis and death at a cost, while increasing the risk of recurrence of non-fatal bleeding.

Background: The rate of major bleeding in patients with atrial fibrillation receiving oral anticoagulants is 25% per year. Gastrointestinal bleedings are at least a half of major hemorrhagic complications. Currently, there is no optimal scale to calculate the risk of bleeding, and therefore the search for clinical predictors of gastrointestinal bleeding remains relevant., Aim: To assess the frequency and structure of large gastrointestinal bleeding, as well as to identify clinical predictors of their development based on long-term prospective observation of patients with atrial fibrillation receiving oral anticoagulants., Materials and Methods: Data were obtained from single center prospective REGistry of long-term AnTithrombotic TherApy (REGATTA NCT043447187). Investigation based on a 20-year follow-up with 510 patients with atrial fibrillation with a high thromboembolic risk (median CHA2DS2-VASc was 4 points). The REGATTA registry assessed the frequency and structure of major gastrointestinal bleeding. Predictors of the development of 32 large gastrointestinal bleeding were identified based on the analysis of pairs with univariate and multivariate analyses., Results: The frequency of major gastrointestinal bleeding in patients with atrial fibrillation receiving oral anticoagulants at 1 year was 1.42 per 100 patients; the predominant localization was upper gastrointestinal tract. Predictors of the development of major gastrointestinal bleeding according to multiple regression data analysis were hemoglobin level 14.55 g/dL, body mass index 28.4 kg/m2, gastrointestinal ulcer or erosive lesion and major hemorrhagic complications in history of disease. In 1/2 cases the sourse of bleeding remained unclear., Conclusion: Searching for clinical predictors of gastrointestinal bleeding can identify patients receiving oral anticoagulants who is need of intensive monitoring risk factors to prevent the development of life-threatening bleeding and to provide with adequate anticoagulant therapy.

Aim: To analyze the frequency of resumption of anticoagulant therapy (ACT) after major and clinically significant bleeding among AF patients who received oral anticoagulants and were observed in the Department of clinical problems of atherothrombosis from 1999 to 2019 within the retro-prospective register Regata-2, and to search for clinical factors associated with recurrence of hemorrhagic complications among patients who resumed anticoagulant therapy after a bleeding episode., Materials and Methods: In cohort study of patients with high-risk AF with absolute indications for ACT we enrolled 290 AF patients (130 women and 160 men) aged 32 to 85 years (the average age was 65.188.89 years). During the follow-up period, 92 patients developed hemorrhagic complications, and 73 of them resumed ACT. 35 of the 73 patients who resumed ACT developed a relapse of major/clinically significant bleeding., Results: The frequency of resuming ACT after the first hemorrhagic complication increased over time from 75% in the period from 19992003 to 90% in the period 20152019. We were not able to establish an exact relationship between the presence of concomitant pathology and the decision to resume the ACT after bleeding. The only reliable reason for refusing to resume the ACT was the patients categorical reluctance. Among patients who had recurrent hemorrhagic complications, the total score on the Charleson comorbidity scale was significantly higher (4.232.01vs3.521.43;p=0.0425). Patients with recurrent bleeding were significantly more likely to suffer from CKD with a decrease in GFR less than 60 ml/min/1.73 sq. m, and also had a history of erosive and ulcerative lesions of the gastrointestinal tract. There was also a significant Association of recurrent bleeding with the use of proton pump inhibitors. Subgroups of patients who switched from warfarin to taking direct oral anticoagulants after the first bleeding and subsequent recurrent bleeding did not differ in basic clinical characteristics from patients without bleeding after changing the anticoagulant. According to multiple regression analysis, NSAIDs showed a tendency to develop a relapse of B/C bleeding on the background of direct oral anticoagulants in patients who underwent GO on the background of warfarin therapy (b=0.4524,p=0.0530)., Conclusion: During the 20-year follow-up, the frequency of all major and clinically significant bleeding was 2.6/100 patients-years, the frequency of first bleeding was 5.86/100 patients-years, while the frequency of repeated hemorrhagic complications was 7.06/100 patients-years. Patients with a high thromboembolic risk should receive anticoagulants, provided that the modifiable risk factors for bleeding are carefully corrected.

Aim: To evaluate efficacy and safety of reduced dose of direct oral anticoagulants (DOACs) as part of triple antithrombotic therapy in AF patients, undergoing elective percutaneous coronary intervention (PCI), and to identify factors, associated with this strategy., Materials and Methods: The study is a cohort analysis of AF patients with AF, who successfully underwent elective PCI and assigned DOACs as part of triple antithrombotic therapy (TAT).Influence of a reduced DOACs dose as a part of TAT on the frequency of thecomposite efficacy endpoint (acute coronary syndrome, ischemic stroke, venous thromboembolic events, cardiovascular death and angina pectoris aggravation/need for unplanned PCI) and safety endpoint (hemorrhagic complications BARC types 2-5) were assessed using the Log-Rank criterion., Results: The study included 124 pts (69.4% women, mean aged 69±8.2 years). Themedian total score CHA2DS2-VASc was 5, the median of the Charlson index composed 7. Half (52%) of AF patients with high risk of thrombotic events after elective PCI received reduced-DOACs dose. Median follow up period was 11.0 month. 17 adverse thrombotic events were recorded during this period, BARC 2-5 bleedings occurred in 27 patients. Reduced DOACs doses in AF patients undergoing PCI were associated with significant increase of thrombotic events during follow up period compared to patients received full DOACs doses (0.79 vs 0.93, Log-Rank p=0.0292). Patients, who received full and reduced DOAC doses, were comparable in the frequency of BARC 2-5 bleedings (0.78 vs 0.75, Log-Rank p=0.06742)., Conclusions: The administration of a reduced DOACs dose as a part of TAT in patients with AF, who underwent PCI, was associated with significant increase in the incidence of all thrombotic events, compared to patients, who received full dose of anticoagulants. The number of hemorrhagic complications was comparable.

Aim: to compare two anticoagulant therapy (ACT) regimens in the treatment of venous thrombosis (VT) in patients after catheter interventions - electrophysiological studies (EFIs) and ablations: enoxaparin followed by warfarin, and rivaroxaban monotherapy., Materials and Methods: The study included patients from 18 years and older with heart rhythm disorders and planned catheter ablation. When parietal venous thrombosis (VT) were detected at the femoral vein puncture site, all patients were randomly assigned to two treatment groups. In group I enoxaparin 1 mg/kg was prescribed every 12 hours with switching to warfarin after 7 days with maintenance of the target INR values (2.0-3.0). In group II rivaroxaban therapy was started at a dose of 15 mg twise/day for 21 days with a further transition to a dose of 20 mg/day. The total period of observation and treatment of patients was at least 3 months., Results: 408 patients were observed, 42 (10.3%) patients with parietal VT were divided into two treatment groups. In group I (n=16) complete lysis of VT was noted by the 7th day of treatment in 7 (58.3%) patients, however this scheme was associated with a greater risk of complications (р=0.003) at the puncture site in the form of arteriovenous fistulae (n=1; 8.3%) and intermuscular hematomas (n=4; 25%). In group II (n=26), no complications were noted, the lysis time of VT was on average 21 days (n=18; 69.2%). Complete lysis of VT was noted in both groups at the time of the control observation point (3rd month)., Conclusion: The efficiency of the two VT treatment regimens was comparable. Enoxaparin therapy is associated with a high risk of local complications, namely intermuscular hematomas (n=4; 25%) and arteriovenous fistulas (n=1; 8.3%). Rivaroxaban monotherapy is safer (p=0.003); in Group II none of the patients had any complications.

Aim: To investigate the prognostic value of renal function and to estimate glomerular filtration rate (GFR) changes during a 5-year follow-up of patients receiving warfarin therapy., Subjects and Methods: 200 patients (124 men, 76 women) mainly from a group at high risk for thromboembolic events (mean CHA2DS2-VASc scores, 3.25±1.89) were examined. The patients' mean age was 62.3±9.4 years; the follow-up period was 5 years. 74% of the patients received warfarin monotherapy (international normalized ratio (INR) 2.0 to 3.0); 36% took vitamin K antagonists in combination with one or two antiplatelet agents. The CKD-EPI formula was used to estimate GFR in all the patients at baseline and throughout the investigation once a year., Results: GFR less than 70.9 ml/min/1.73 m2 was found to be a predictor of fatal and nonfatal thrombotic events. The decreased GFR was unassociated with the development of major and clinically relevant hemorrhagic complications within 5 years of warfarin therapy. The initial decline in renal function (GFR <70.9 ml/min/1.73 m2) was associated only with an increased rate of recurrent minor hemorrhagic complications. During 5-year warfarin therapy, there was a significant decrease in GFR from 97.1±24.85 to 91.9±28.9 ml/min/1.73 m2; at the same time, a rapidly progressive loss of renal function (GFR ≥3 ml/min/1.73 m2/year) was recorded in 25.9% of the patients. Discriminant analysis showed that a baseline left ventricular ejection fraction of <40% was a predictor for the rapidly progressive loss of kidney function., Conclusion: Long-term warfarin therapy achieved the therapeutic range for INR is safe in the environment of the created patronage system. The initial decrease in GFR is a predictor of thrombotic events and is unassociated with an increased risk of bleeding.

Aim: To analyze efficiency of semi-quantitative fast D-dimer test in diagnosis of deep vein thrombosis (DVT) and thromboembolism of pulmonary artery (TPA)., Material and Methods: The study enrolled 42 patients (26 males and 16 females) aged 25 to 86 years. 30 and 12 of them were suspected to have DVT and TPA, respectively. DVT was verified at ultrasound dopplerography and radionuclide phlebography in 16 of 30 suspects. TPA was verified by x-ray, perfusion scintigraphy of the lungs and at autopsy (one case) in 7 of 12 suspects. D-dimer levels in the blood were measured by latex parts agglutination reaction. The parts were covered with monoclonal antibodies to D-dimer. The reagents were provided by the kit Roche/Diagnostica Stago., Results: The D-dimer test was positive in 20 of 23 DVT patients and negative in 3 cases (13%). Of 19 patients with rejected diagnosis of DVT/TPA the test was negative in 17(89.4%) and positive in 2 patients (10.6%). Thus, sensitivity and specificity of the D-dimer test was 87% and 89.4%, respectively., Conclusion: High sensitivity of the test allows to use it in screening for DVT/TPA. Negative D-dimer test rejects DVT, while positive test needs verification by other methods.