Chronic Kidney Disease is a Predictor of Recurrent Bleeding in Patients With Atrial Fibrillation After Resuming Anticoagulant Therapy (based on REGistry of Long-term AnTithrombotic TherApy (REGATA-2).

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.

[Resumption of anticoagulant therapy after major bleeding and the risk of negative events in patients with atrial fibrillation (based on REGistry of Long-term AnTithrombotic TherApy-2 - REGATA)].

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.

[Severe gastrointestinal bleeding in patients with atrial fibrillation receiving oral anticoagulants (based on REGistry of long-term AnTithrombotic TherApy - REGATTA)].

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.

[Resumption of anticoagulant therapy after major bleeding and recurrence of hemorrhagic complications in patients with atrial fibrillation with a high risk of stroke and thromboembolism (based on the results of 20 years of observation)].

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.

[Renal function in patients receiving long-term warfarin therapy: A five-year prospective follow-up]. / Funktsiia pochek u bol'nykh, dlitel'no prinimaiushchikh varfarin (5-letnee prospektivnoe nabliudenie).

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.

[HAS-BLED and HEMORR2HAGES Scales in Assessment of Bleeding Risk in Patients on Long-Term Warfarin Therapy].

UNLABELLED: 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. CYP2C9 and VKORC1 (G3673A) genotypic variants were determined by PCR. Patients were divided into low (< 3 points of HAS-BLED scale, n = 58; < 4 points of HEMORR2HAGES scale, n = 109) and high (3 points of HAS-BLED scale, n = 61, ≥ 4 points of HEMORR2HAGES scale, n = 10) bleeding risk groups. RESULTS: There was no relationship between total HAS-BLED, HEMORR2HAGES scores and numbers of all as well as category 1 and 2 bleedings. The difference in bleeding frequency between high and low risk groups was significant only for recurrent bleedings. There were 22 (36.1%) and 5 (8.6%) recurrent bleedings among 61 and 58 patients with high and low-risk HAS-BLED score, respectively (p = 0.0048). Recurrent bleedings also occurred more frequently among patients with high risk (7/10, 70%) compared with low risk (20/109, 18.35%) HEMORR2HAGES score (p = 0.018). Subgroups of high and low bleeding risk according to HAS-BLED and HEMORR2HAGES scores differed only by proportion of patients with recurrent bleedings. High W sensitivity represented by 2*/2*, 2*/3*, 3*/3* CYP2C9 and/or AA VKORC1 homozygosis was detected in 25 of 119 patients. Six of 8 patients (75%) with category 1 bleedings were carriers of any polymorpism. CONCLUSION: HAS-BLED and HEMORR2HAGES scales performed best in predicting recurrent bleedings in patients on long term W therapy. Single bleedings with INR > 4.0 during 1st month of W therapy were associated with reduced W metabolism (AA VKORC1 or/and CYP2C9 allelic variants 2*/2*, 2*/3*, 3*/3*).

[HAS-BLED and HEMORR2HAGES Scales in Assessment of Bleeding Risk in Patients on Long-Term Warfarin Therapy].

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.