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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.

Aim: Patients with atrial fibrillation (AF) at high risk of thromboembolic complications who have had bleeding should strive to resume anticoagulant therapy. Existing traditional scales for assessing the risk of hemorrhagic complications are not highly specific for the risk of recurrent bleeding. Thus, searching is needed for clinical and laboratory predictors to identify patients who require a personalized monitoring regimen. The aim of the study was to assess the incidence rate and predictors of recurrent major and clinically significant bleeding in patients with AF after resumption of the anticoagulant therapy, as well as the contribution of changing the anticoagulant to the treatment safety., Material and Methods: Based on a 5-year follow-up of 95 patients with AF who have had major and clinically significant bleeding, the incidence and clinical factors determining the recurrence of hemorrhagic complications were assessed.Results According to the data of the 5-year follow-up, the recurrence rate of major/clinically significant bleeding was 16.9/100 patient-years. Changing the oral anticoagulant significantly reduced the risk of relapse after clinically significant bleeding and did not affect the risk of recurrence of major bleeding. The predictor for relapse of major/clinically significant bleeding during the therapy resumption was chronic kidney disease with a decrease in creatinine clearance to less than 60 ml/ min, which increased the risk of relapse 2.27 times (95% confidence interval: 1.1253-4.6163; p=0.0221)., Conclusion: The development of serious bleeding in a patient at high risk of thrombotic complications always requires a reassessment of risk factors and an adequate choice and dosage of the anticoagulant. Development of a unified protocol for the management of AF patients receiving anticoagulants and having a high risk of bleeding is essential and will reduce the risk of adverse outcomes.

Background: The role of albuminuria as a marker of the atherosclerosis burden and a predictor of prognosis in patients with polyvascular disease (PD) has been little studied., Aim: To evaluate the prevalence, association with atherosclerosis burden, and prognostic value of albuminuria in relation to cardiovascular and bleeding complications in patients with PD., Materials and Methods: The data was obtained from the prospective registry REGATA-1 (NCT04347200). Seventy four patients (75.7% males, median age 67 [61-69] years) with PD (CAD and peripheral arterial disease) were enrolled. All patients received aspirin and rivaroxaban 2.5 mg. The albumin-creatinine ratio in a single morning urine sample, estimated glomerular filtration rate (eGFR), and von Willebrand factor levels were determined., Results: Mild albuminuria (10-29 mg/g) was detected in 45.9% of patients, moderate and severe (≥30 mg/g) - in 29.7%; eGFR<60 ml/min - in 21.7%, chronic kidney disease (CKD) according to the full KDIGO criteria (eGFR and/or albuminuria ≥30 mg/g) - twice as often (39.2%). The frequency of nephroprotective therapy prescription was insufficient. The level of albuminuria did not correlate with von Willebrand factor (endothelial dysfunction marker), but was associated with affecting of 4-5 vascular beds (ROC AUC 0.775; p =0.011). During the follow-up (12 [8-18] months) 3 patients developed MACE, 11 - BARC 2-3 bleedings. Neither albuminuria nor eGFR were predictors of MACE, bleeding, or net clinical benefit. CKD (KDIGO) was also not associated with bleedings. CKD (KDIGO) was independent predictor of MACE (in significant multiple regression model beta - coefficient for CKD was 0.097; p =0.042), however, the small number of end points allows us to speak only of a hypothesis-generating trend. The implementation of CKD (KDIGO) has increased the predictive value of the REACH score., Conclusion: Albuminuria is highly prevalent in patients with PD. It is a marker of atherosclerosis burden. CKD, diagnosed taking into account the level of albuminuria, can be used in a comprehensive assessment of cardiovascular risk in this category of patients.

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.

А clinical case of a young patient with recurrent ischemic strokes is presented. The problems of diagnostic embolic strokes are discussed. We set out the algorithm for identifying patients, in whom patent foramen ovale is the most probable cause of embolic stroke. Detailed consideration of imaging diagnostic methods possibility is included. Hypothesis of probable source of cardioembolism from patent foramen ovale is presented. Recommendations for the secondary prevention of recurrent ischemic stroke, associated with patent foramen ovale, are provided. We also considered the issues of antithrombotic treatment.

On December 13, 2021, an expert council was held to determine the position of experts of different specialties regarding the reasons for the low level of diagnosis of chronic thromboembolic pulmonary hypertension (CTEPH) in real clinical practice in a pandemic of a new coronavirus infection and possible ways to improve detection in patients with pulmonary embolism (PE) ) in history. The reasons for the low level of diagnosis of CTEPH are the insufficient level of knowledge of specialists, especially primary care physicians; lack of clear regulatory documents and expert centers for the management of this category of patients. Primary diagnosis of CTEPH in a pandemic can be strengthened through the widespread use of telemedicine for consultations of primary care physicians with specialists from expert centers; to maximize the role of echocardiography and computed tomography (CT) as differential diagnostic tools for dyspnea, in particular in patients with COVID-19. To increase the detection rate of CTEPH, diagnostic vigilance is required in patients with risk factors and episodes of venous thromboembolism. To improve the screening of CTEPH, it is necessary to create an algorithm for monitoring patients who have had PE; provide educational activities, including through the media; create materials for patients with accessible information. The regulatory documents should designate the circle of responsible specialists who will be engaged in long-term monitoring of patients with PE. Educational programs are needed for primary care physicians, cardiologists, and other physicians who come into the field of view of patients with CTEPH; introduction of a program to create expert centers for monitoring and managing patients with the possibility of performing ventilation-perfusion lung scintigraphy, cardiopulmonary stress test, CT, right heart catheterization. It seems important to build cooperation with the Ministry of Health of Russia in order to create special protocols, procedures for managing patients with PE and CTEPH.

The key side effects of antiplatelet therapy are associated with the damage of the upper gastrointestinal tract (GIT) mucous that can lead to erosions or ulcers and specifically complicated by bleeding., Aim: To assess the upper gastrointestinal mucosal condition by endoscopic and histological methods in patients with stable coronary arteries disease receiving long-term antiplatelet therapy with gastrointestinal bleeding (GIB) history or with high risk of this complication., Materials and Methods: The study included patients from the single-center prospective registry of long-term antithrombotic therapy REGATTA-1. The gastric mucosa endoscopic examination with biopsy was performed in 20 patients with gastrointestinal bleeding history less than 1 year ago and in 24 patients without GIB, which have concomitant risk factors such as erosions and ulcers history and/or persistent dyspepsia clinical signs. The mucosal condition (erosions and ulcers) was estimated using a modified Lanz scale. The presence of Helicobacter pylori was determined by Histological verification. The inflammatory process characteristics were evaluated according to the modified Sydney classification. All participants received antithrombotic therapy at the time of esophagogastroduodenoscopy; 81.8% of patients received proton pump inhibitors., Results: Chronic inflammation (93.2%), atrophy (59.1%), multiple erosions (45.5%) or ulcers (18.2%) were the most frequent endoscopic finding. H. pylori infection, found in mucosal samples in 90.9% of patients was one of the most important pathogenesis mechanism, which support the gastrointestinal mucosa damage., Conclusion: Mucosal damage endoscopic signs remains despite long-term proton pump inhibitors therapy in patients with coronary arteries disease and concomitant GIB risk factors, receiving antithrombotic therapy. H. pylori contamination may be the cause of these changes. Therefore, its active screening and eradication is necessary in such patients.

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.

On December 18, 2020, an expert council was held with the participation of members of the Russian Society of Cardiology, the Eurasian Association of Ther-apists, the National Society for Atherothrombosis, the National Society for Evi-dence-Based Pharmacotherapy, and the Russian Heart Failure Society. The event was devoted to the discussion of the correct use of research data of "real clinical practice" in decision making.

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      Searching for clinical, angiographic, and biochemical predictors of cardiovascular complications (CVC) and hemorrhagic complications in patients with atrial fibrillation (AF) receiving a multicomponent antithrombotic therapy (MAT) for an elective percutaneous coronary intervention (PCI). Patients with ischemic heart disease (IHD) and AF who require MAT for PCI are at a high risk of thrombotic complications (stroke, systemic embolism, coronary events) and hemorrhage. This warrants searching for new risk factors determining prediction of the outcome.Materials and methods This study included 207 patients (146 males aged 70.1±8.3 years) with IHD and AF who received direct oral anticoagulants (DOAC) as a part of their MAT therapy. Median duration of the follow-up was 12 [8.0; 12.0] months. The efficacy endpoint was a sum of CVCs combining cardiovascular death, ischemic stroke, venous thromboembolic complications, acute coronary syndrome (ACS), and requirement for an unscheduled PCI. "Coronary events", including ACS and requirement for an unscheduled PCI were analyzed separately. The safety endpoint was BARC type 2-5 bleeding. Upon admission, biomarkers (growth-differentiation factor 15 (GDF-15), D-dimer, thrombin-activated fibrinolysis inhibitor (TAFI), and plasminogen activator inhibitor-1 (PAI-1)) were measured for all patients. Searching for prognostically significant indexes was performed with the Cox proportional hazards regression.Results Incidence of all CVCs was 16.4 %. Independent predictors of CVC included the DOAC treatment at a reduced dose (odds ratio (OR) 2.5 at 95 % confidence interval (CI) 1.02-6.15; p=0.0454), GDF-15 &gt;1191 pg /ml (OR 3.76 at 95 % CI, 1.26-11.18; p=0.0172), PAI-1 &gt;13.2 U/ml (OR 2.67 at 95 % CI, 1.13-6,26; p=0.0245). Incidence of coronary complications was 9.2 %. Independent predictors of coronary complications included a SYNTAX index &gt;26.5 (OR 4.5 at 95 % CI, 1.45-13.60; p=0.0090), PCI for chronic coronary occlusion (OR 3.21 at 95 % CI, 1.10-9.33; p=0.0326), a GDF-15 &gt;1191 pg/ml (ОR 4.70 at 95 % CI, 1.32-16.81; p=0.0172). Incidence of BARC type 2-5 bleeding was 26.1 %. The only independent predictor for hemorrhage complications was the total PRECISE-DAPT score &gt;30 (ОR 3.22; 95 % CI, 1.89-5.51; р&lt;0.0001).Conclusion      Three independent predictors of CVC were identified for patients with IHD and AF treated with MAT following an elective PCI: treatment with a reduced dose of DOAC, GDF-15 &gt;1191 pg /ml, and PAI-1&gt;13.2 U/ml. Independent predictors of coronary complications included a SYNTAX index &gt;26.5, PCI for chronic coronary occlusion, and GDF-15 &gt;1191 pg/ml. The factor associated with a risk of bleeding was the total PRECISE-DAPT score &gt;30.

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.

History of antithrombotic therapy in cardiology has almost 70 years, and it is undoubtedly the importance of the achievements of Soviet scientists. The creation of a domestic thrombolytic fibrinolysin at MSU G. V. Andreenko, its first successful application in patients with myocardial infarction (MI), conducted by E. I. Chazov, and then by other domestic researchers, played a crucial role in proving the need for a quick restoration of the patency of infarct related artery. The world's first intracoronary thrombolysys, conducted by E. I. Chazov, together with the staff of the all-Union cardiological center, allowed to verify thrombosis as the cause of MI and demonstrate the effectiveness of thrombolytic therapy. One of the most important achievements of domestic researchers of the 60s of the last century was the understanding of the need not only to eliminate the thrombus by using of fibrinolysin, but also to prevent its recurrence, with administration of heparin with transition to VKA. This conclusion, in fact, is a statement of the need for long - term antithrombotic therapy in patients with сoronary artery disease (CAD). Over the past 70 years, antithrombotic therapy in CAD has undergone significant changes, this was facilitated by the undoubted progress in understanding the mechanisms of atherosclerosis and thrombosis development. Nevertheless, the basic principles of antithrombotic therapy, laid down by the national school in the 60s of the last century, have survived.

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.

The VerifyNow assay is based upon the ability of activated platelets to cross-link beads coated with fibrinogen. However, fibrinogen is an abundant protein of blood, and therefore it may affect test results by competing with fibrinogen of beads for binding to platelets. To test this assumption, we assessed the influence of artificial alteration of fibrinogen level in blood samples obtained from donors (n = 9) and patients on clopidogrel therapy (n = 8) on the results of the VerifyNow P2Y12 assay. Fibrinogen level was altered by adding to blood samples 1/10 volume of fibrinogen solution (10.56 g/liter) or corresponding buffer. Relative to baseline, addition of buffer significantly increased platelet reactivity, whereas addition of fibrinogen decreased it. Analysis of the relationship between change in platelet reactivity values (dBase and dPRU) and change in fibrinogen concentration (dFg) revealed strong negative correlations: dBase = -63.3 × dFg - 27.1 (r = -0.924, p < 0.0005) and dPRU = -54.4 × dFg - 21.8 (r = -0.764, p < 0.0005). Thus, the results of our experiments suggest that: (i) blood fibrinogen strongly influences results of the VerifyNow P2Y12 assay, and (ii) correcting for fibrinogen effect may be needed to improve the accuracy of the test in the measuring of antiplatelet effect of clopidogrel therapy.

Aim: to investigate parameters of fibrinolysis in patients on long-term warfarin (W) therapy, and assess their relation to the risk of recurrent bleeding occurring at therapeutic international normalized ratio (INR)., Materials and Methods: Our prospective study involved 78 W-naive patients (40 men, age 64.3+/-12.2 years). Follow up period was 5.6+/-3.4 months. INR was measured monthly; determination of coagulation parameters (D-dimer, fibrinogen, complex plasmin-2-antiplasmin [PAP] and thrombin-activatable fibrinolysis inhibitor [TAFI] was performed before and after at least 3 months of W therapy., Results: During follow-up bleedings occurred in 47 (60.3%) patients, 26 patients (33.3%) had recurrent bleedings at therapeutic INR and 21 patients (26.9%) had single bleeding. Mean time in therapeutic range (TTR) was >70.

Aim of the study was to elucidate value of HAS-BLED and HEMORR2HAGES scales for prediction bleedings in patients receiving long-term warfarin (W) therapy., Material and Methods: The study involved 119 patients (72 men) aged 60.9+/-9.6 years with atrial fibrillation or venous thromboembolic complications. Follow up period was 5.6 +/-3.4 years. All bleedings were categorized as 1) single bleeding with INR>4.0 during the 1st month of W therapy; 2) any single bleeding after 1st month of W therapy; 3) recurrent bleedings. CYP29 and VKORC1 (G3673A) genotypic variants were determined by PCR. Patients were divided into low (<3 points of HAS-BLED scale, n=58; <4 points.

Risk stratification seems to be very important in patients with stable coronary artery disease (CAD). However, the prognostic scales are now available only for the early risk assessment in patients with acute coronary syndromes and in patients undergoing percutaneous coronary interventions. Aim of the study was to assess the frequency of cardiovascular events (CVE) during 5 years of follow-up in patients with stable CAD and to construct a long-term risk prediction model for these patients. 503 patients (mean age 59.4 years) were included in the study. The follow-up period ranged between 3.0 and 7.5 years (mean 5.0 years). Main end points were fatal and non-fatal cardiovascular events: cardiovascular death, acute coronary syndromes, ischemic stroke, transient ischemic attack, peripheral arterial thrombosis, and need for revascularization in any affected vascular area. Total frequency of events was 31.0% (5.7/100 patient years). Independent predictors of events were: severity of angina, three vessel coronary disease, previous myocardial infarction, previous stroke/ transient ischemic attack, peripheral arterial disease, obesity, chronic kidney disease and history of erosive gastritis. The presence of more or equal 3 risk factors was significantly associated with increased frequency of CVE.

Despite high immediate efficacy of percutaneous coronary interventions (PCI) in relation to symptoms of angina the problem of influence of this method of treatment on duration of life and prognosis in stable ischemic heart disease (IHD) remains unsolved. Aim of our study was to compare efficacy of conservative therapy with drugs of proven effect on prognosis and of percutaneous coronary interventions in combination with optimal drug therapy in patients with stable ischemic heart disease (IHD) during 5 years of follow up. We included into this study 503 patients (387 men and 116 women, mean age 59 years). Groups of conservative and invasive treatments comprised 179 and 302 patients, respectively; mean durations of follow-up were 5.6+/-1.3 and 4.1+/-1.6 years, respectively, p=0.001. Study end points were fatal and nonfatal cardiovascular complications (CVC) (cardiovascular death, acute coronary syndrome, transitory ischemic attack, peripheral arterial thrombosis) and composite endpoint defined as sum of all CVC and cases of revascularization of the involved vascular bed. Cumulative rates of all fatal and nonfatal CVCs was 5.3 and 4.8 per 100 patient/years in groups of conservative and invasive treatment, respectively (relative risk [RR] 0.96, 95% confidence interval [CI] 0.6 to 1.5; p=0.9). Rates of composite end point were 7.1 and 7.3 per 100 years in groups of conservative and invasive treatment, respectively (relative risk [RR] 1.02, 95% confidence interval [CI] 0.7 to 1.3; p=0.8). According to the presence of independent clinical predictors of worst prognosis (class II-III angina, history of myocardial infarction, three vessel or left main stem coronary artery disease, concomitant signs of atherothrombosis in cerebral and peripheral vascular beds, obesity, abnormal renal function, history of erosive gastritis) all patients were divided in groups of low, moderate, and high risk. In low risk IHD patients invasive strategy worsened remote prognosis of myocardial infarction, stroke, and cardiovascular death, as well as of repetitive revascularization.

The review is devoted to pharmacogenetics of clopidogrel and its value for the clinic. Mechanism of action of clopidogrel and main trials which has proven its efficacy are presented as well as results of main large studies including authors own results demonstrating dependence of clinical efficacy of clopidogrel on carriage of polymorphisms of gene of CYP2C19 which accomplishes metabolism of the drug in the liver. Problems of interaction of clopidogrel with proton pump inhibitors and other drugs as well as ways of overcoming "resistance" to clopidogrel are considered. Clinical efficacy of other P2Y12 receptors of platelets in patients with IHD is characterized in comparison with clopidogrel.

The study included 25 patients at high risk of thromboembolic complications. All of them were treated with acenocoumarol for 6 months under control of the frequency of hemorrhage and episodes of severe hypocoagulation (a more than 3-fold rise in INR). All the patients underwent CYP2C9 and VKORC1 genotyping. It was shown that the presence of CYP2C9*2 and CYP2C9*3 alleles in the CYP2C9 locus and the AA genotype of the polymorphous G-1639(3673)A marker of the VKORC1 gene was not associated with the development of severe hypocoagulation episodes (p = 0.261--for CYP2C9, p = 0.616 and 0.361 for VKORC1 in the total group and a subgroup of patients having the CYP2C9*1/*1 genotype respectively and treated with acenocoumarol. The search for other genetic markers of efficacy and safety of this drug should be continued.

Aim: To compare effects of prolongation of the treatment with therapeutic doses of enoxaparin to 1 month on recanalization of occlusively thrombosed deep veins (OTDV) of the limbs with results of standard therapy with unfractionated heparin (UFH). Both treatments were followed by warfarin administration., Material and Methods: Thirty patients were selected from 111 patients with a history of deep vein thrombosis (DVT) and/or pulmonary artery embolism according to the following criteria: the presence of occlusive thrombosis of one deep vein minimum; the absence of DVT for 12 months of follow-up. Patients of group 1 (n = 15) received standard therapy (UFH for at least 5 days) with switch to warfarin. Patients of group 2 (n = 15) received therapeutic doses of enoxaparin (1 mg/kg each 12 hours) for 30 days minimum with switch to warfarin. Follow-up was 12 months. Ultrasonic duplex angioscanning of the limbs was made at baseline, 1, 3, 6 and 12 months after treatment start., Results: After follow-up month 1, 3 and 6 number of patients with occlusive DVT was significantly less in group 2. All the patients given enoxaparin achieved recanalization of OTDV within 3 months of treatment. OTDV recanalization was not achieved in 20% patients of group 1 even 12 months after treatment start., Conclusion: Prolongation of enoxaparin treatment to 1 month followed by warfarin treatment is superior to standard UFH treatment followed by warfarin in providing recanalization of OTDV within 3 months of treatment. Moreover, this treatment predicts persistence of recanalization within 12 months of anticoagulant therapy.

Aim: To study effects of thrombin-activated fibrinolysis inhibitor (TAFI) on efficacy and safety of long-term anti-coagulant treatment in patients with venous thromboembolic complications (VTEC)., Material and Methods: A total of 111 patients with a history of an episode of deep vein thrombosis (DVT) and/or pulmonary artery thromboembolism (PATE) entered the study. All the patients received unfractionated or low-molecular heparin for at least 5 days than switch on warfarin (target values of INR 2.0-3.0). Baseline blood levels of TAFI were measured. The patients were followed up for 18 months. Recurrent (DVT/TAFI and hemorrhagic complications (HC) were endpoints. Also, frequency of complete lysis of deep vein thrombi was assessed after 12 months of treatment., Results: A TAFI level varied from 50 to 217% (median 106%, interquartile rage 90-133%). TAFI concentration positively correlated with fibrinogen and thromb size. The patients were divided into two groups depending on TAFI content: group 1 patients had low TAFI (under 25th percentile; < 90%); patients of group 2 had high TAFI (above 25th percentile; > 90%). Group 1 patients were characterized by less stable anticoagulation. This association did not depend on genetic characteristics which determine sensitivity to warfarin (CYP2C9 and VKORC1). Low TAFI was associated with reduced risk of DVT for 18 months and higher probability of complete lysis of the thrombi after 12 months of anticoagulant therapy compared to VTEC patients with high TAFI. No differences were found by TAFI level in patients with HC and without HC, but in HC patients low TAFI was associated with spontaneous hemorrhages and bleeding in therapeutic INR values., Conclusion: The results of this pilot study evidence that a TAFI level can be one of the factors influencing efficacy and safety of long-term anticoagulant therapy in patients with VTEC on warfarin treatment.