Use Of New Oral Anticoagulants Research Articles

The highlights of dialysis in 2023

There has been a wealth of new developments in dialysis this year with the publication of several trials relating to dialysis technique, physical activity and the use of new dialysis treatments. Quality of life should be assessed and managed in all dialysis patients. Lowering the temperature of the dialysis bath in the MyTemp trial does not appear to have an effect on mortality and cardiovascular events. High volume convective hemodiafiltration currently represents the reference technique in hemodialysis; the Convince study confirms its superiority in terms of all-cause mortality. The DIATT study shows the benefit of the presence of an adapted physical activity professional to promote physical activity in dialysis patients and shows that it is necessary for this support to be reimbursed. The RENAL-AF and AXADIA-AFNET 8 studies lack power to conclude on the use of new oral anticoagulants in hemodialysis. For angiotensin receptor neprilysin inhibitors, studies are too weak to allow their use. SGLT2 inhibitors could be used in peritoneal dialysis to increase diuresis or delay the appearance of peritoneal fibrosis but to date only studies on models animals exist. Factor XI inhibitors are a new therapeutic class that could be used and would reduce the risk of thrombosis and hemorrhage. Increasingly, the feelings of patients and caregivers are more and more taken into account. Patient/caregiver communication must be at the heart of care. We will also be looking at the conservative treatment, the management of pruritus in hemodialysis and finally the care of patients with calciphylaxis.

Multiple thromboses, including intracardiac thrombi, accompanied by HIT during ECMO successfully treated with NOACs: A case report.

Unfractionated heparin remains the mainstay of anticoagulation therapy during extracorporeal membrane oxygenation (ECMO) maintenance. However, its continued use in clinical practice exposes patients to the risk of developing heparin-induced thrombocytopenia (HIT). A 50-year-old male was diagnosed with multiple thromboses, including an intracardiac thrombi, accompanied by HIT during ECMO after cardiogenic shock related to acute myocardial infarction. The patient was successfully treated with new oral anticoagulants (NOAC), without significant complications. HIT during ECMO resulting in multiple thromboses is rare. To our knowledge, this is the first reported case of NOAC use in this context. Although thrombocytopenia and thrombosis can occur for various reasons during ECMO maintenance, it is important to consider HIT as a potential cause. NOACs can be considered as a therapeutic option.

Atrial fibrillation and dementia: not everything is clear…

The prevalence of dementia is ever increasing, as well as the prevalence of atrial fibrillation (AF). Several studies and systematic reviews evaluated the association between AF and dementia, highlighting an increased risk for dementia (with odds ratios from 1.4 to 1.6), with robust results in patients with previous stroke. In fact, not only vascular dementia, but also Alzheimer's disease seems more frequent in patients with AF, even though the very high heterogeneity of the results does not allow for solid conclusions. One of the mechanisms by which AF can cause dementia is the presence of silent embolic cerebral infarctions, and therefore treatment with oral anticoagulants could reduce the incidence of dementia. The results of several studies and systematic reviews show that this therapy, particularly with the new oral anticoagulants, is associated with a reduction of approximately one third of dementia. Rhythm control, obtained either with pharmacological therapy or catheter ablation, is associated with a reduction of dementia impact as well. The association between AF and cognitive deficit is therefore well documented, being more evident in patients with previous stroke but also present in cohorts of patients without prior vascular events. The development of dementia in AF patients can be due to cerebral infarctions, both clinically evident or silent, as well as by microembolism, microbleeds and hypoperfusion. Oral anticoagulation, particularly with the use of new oral anticoagulants, as well as a rhythm control strategy can reduce the incidence of dementia. More recently, it has been shown that atrial cardiomyopathy is significantly associated with the incidence of dementia, also in patients with no history of AF or stroke.

New Oral Anticoagulants – What’s New? A Systematic Review

Introduction: Anticoagulant therapy is defined as the standard prevention and treatment method for systemic thromboembolism. Thus, despite heparin and vitamin K antagonists being used as traditional methods, the new oral anticoagulants (NOACs), such as activated factor X inhibitors and direct thrombin inhibitors have been emerged, based on their safety and efficacy analyses appropriate to clinical practice, in addition to its convenience in clinical management. Objectives: To evaluate anticoagulant therapy with the use of NOACs. Methods: This is a systematic review, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyzes criteria. Studies from the National Library of Medicine (PubMed.gov) and Embase databases were included, through randomized clinical trials (RCTs), published from 2011 until June 2021, which comprised the investigation question. Data were extracted about the NOACs, the conventional anticoagulant, use in renal patients, clinical outcomes and side effects. Results: 384 results were identified through the search strategy, proceeding to the analysis of 315 after exclusion of duplicates. Then, after the application of the eligibility criteria, 33 studies progressed to full reading and 18 were included in the qualitative analysis of the review. The included studies demonstrated the analysis of specific comorbidities, and most comprised the adult population and warfarin as a conventional anticoagulant used. Edoxaban was the most evaluated NOAC, being included in 7 studies. Bias analysis found 3 “low risk” studies and 7 overall “high risk” studies. Conclusion: The comparison of conventional therapy and NOACs demonstrates similarity in the efficacy clinical outcomes analyzed by the studies, with similar reductions of the risk of thromboembolic events. From the analysis of the occurrence of bleeding, NOACs represent reduced rates of such outcomes. Regarding the analysis of the risk of bias of the studies, 15 of the 18 studies analyzed were classified as “high risk of bias” or as “some concerns”, especially in the criteria of “missing outcome data. In general, although no methodologically strong evidence has been identified about NOACs, their use is a reasonable alternative to conventional therapy in clinical management.

Prescribing patterns of new oral anticoagulants in patients with atrial fibrillation and chronic kidney disease: A narrative review

This study aimed to investigate the prescribing patterns of new oral anticoagulants in atrial fibrillation patients based on creatinine clearance. A thorough analysis of articles published between 2017 and 2021 in databases such as PubMed, Scopus, and Google Scholar was conducted.
 The review revealed distinctive features in the use of new oral anticoagulants concerning glomerular filtration rate. Apixaban was identified as a judicious choice for individuals with kidney disorders, with approximately 25% of its dose excreted in urine. American guidelines specifically recommend apixaban for those with a creatinine clearance of less than 15 mL/min, while European recommendations contraindicate all new oral anticoagulants for such rates.
 In instances where the glomerular filtration rate ranges from 15 to 29 mL/min, apixaban or edoxaban may be preferred due to the substantial renal elimination of edoxaban. Reduced dose regimens of rivaroxaban, edoxaban, and apixaban are advised for individuals with chronic kidney disease and a creatinine clearance between 15 and 30 mL/min.
 Dabigatran, characterized by an 80% renal elimination rate, is recommended for individuals with a creatinine clearance exceeding 30 ml/min according to European guidelines and those with a clearance of at least 15 ml/min according to American guidelines.

#3896 SAFETY OUTCOMES OF ORAL ANTICOAGULANT THERAPY IN PATIENTS WITH ATRIAL FIBRILLATION AND CHRONIC KIDNEY DISEASE

Abstract Background and Aims The comorbid conditions of atrial fibrillation (AF) and chronic kidney disease (CKD) leads to an increased risk of thromboembolic complications, but on the other hand is a risk factor for various bleeding. Oral anticoagulant therapy is the standard for the prevention of thromboembolic complications in AF. But with the deterioration of kidney function, the risk of hemorrhagic complications increases dramatically. This problem makes it difficult to choose an effective and safe oral anticoagulant therapy. Clinical data on the use of new oral anticoagulants (NOACs) in patients with AF and advanced CKD are limited, which determines the relevance of conducting studies in comparison with vitamin K antagonists. The aim of study was evaluation of safety parameters for the using of rivaroxaban in patients with stage 4 CKD with AF. Method The study included 109 patients over the age of 18 with a diagnosis of stage 4 CKD (eGFR – 15–29 ml/min/1.72 m2) and non-valvular AF. They were randomized in a 2:1 ratio to either rivaroxaban 15 mg (n = 73) or warfarin (n = 36). The mean follow-up period was 18 months. In the warfarin group, time in therapeutic range (TTR) >70% was achieved in 34 (94%) patients. Exclusion criteria were a history of bleeding that required hospitalization; decrease in hemoglobin level below 80 g/l, platelet count below 100 × 109/l; indications for taking antiplatelet therapy; chronic use of drugs that increase the risk of bleeding. The analysis of the observed hemorrhagic events was carried out using the BARC and ISTH scales. Classification of anemia was carried out according to the recommendations of the World Health Organization. Results Patients taking warfarin were significantly more likely to develop minor bleeding according to the BARC scales and ISTH and all clinically significant bleeding on the ISTH scale. In patients with AF and CKD receiving warfarin therapy, minor bleeding (MB) according to the BARC scale was observed in 72.2% (n = 26), minor clinically significant bleeding (MCSB) in 8.33% (n = 3), major bleeding in 8.33% (n = 3) of cases; and in the group of patients treated with rivaroxaban, MB was observed in 42.4% (n = 31, p<0.01), MCSB in 2.74% (n = 2, p = 0.32), major bleeding in 2.74% (n = 2, p = 0.32) of cases. When assessing bleeding on the ISTH scale during therapy with VKA, MB – 61.1% (n = 22), MCSB – 19.4% (n = 7), major bleeding – 8.33% (n = 3); against the background of NOACs therapy, MB – 36.9% (n = 27, p = 0.01), MCSB in 8.2% (n = 6, p = 0.06), major bleeding in 2.74% (n = 2, p = 0.32). All clinically significant hemorrhagic events according to the BARC scale in the warfarin group occurred more than 16.6% (n = 6) compared with the rivaroxaban group 5.4% (n = 4, p = 0.06); when analyzed according to the ISTH scale, the number of patients receiving VKA anticoagulant therapy 27.7% (n = 10) significantly prevailed over patients on the background of NOACs 10.9% (n = 8, p = 0.03). Analysis of hemoglobin level did not reveal significant dynamics and significant differences between the groups: the median hemoglobin level at inclusion was 129 g/l in the rivaroxaban group and 123 g/l in the warfarin group (p = 0.3), after 18 months - 130 g/l and 121 g/l, respectively (p = 0.7). Conclusion Data suggesting a favorable safety profile for NOACs (rivaroxaban) compared with VKAs (warfarin) in patients with AF and advanced CKD was obtained in this study. Taking rivaroxaban was accompanied by a significantly lower number of hemorrhagic events, which may indicate a safe effect of the drug. No significant changes in hemoglobin levels were found in both groups. Confirmation of these data may be key in choosing an anticoagulant in patients with AF and advanced CKD.

Oral Anticoagulation and the Incidence of Stroke Associated with Atrial Fibrillation in Mainland Portugal: A Modelling Study

Atrial fibrillation is the most prevalent persistent dysrhythmia, contributing to a significant social and economic burden. The main objective of this study was to evaluate the association between oral anticoagulant use and the incidence of stroke associated with atrial fibrillation, in mainland Portugal. The number of episodes of inpatient care with a main diagnosis of stroke and an additional diagnosis of atrial fibrillation, occurring monthly between January 2012 and December 2018, in individuals aged 18 years or over, was extracted from the hospital morbidity database. The number of patients with an atrial fibrillation code documented in this database was used as a proxy for the prevalence of known atrial fibrillation. The number of anticoagulated patients was estimated from total medicine sales of vitamin K antagonists and novel oral anticoagulants (apixaban, dabigatran, edoxaban and rivaroxaban) in mainland Portugal. Descriptive analyses were performed, and seasonal autoregressive integrated moving average (SARIMA) models were built using the R software. The mean number of episodes of stroke per month was 522 (± 57). The number of anticoagulated patients increased gradually from 68 943 to 180 389 per month. The decreasing trend in the number of episodes has been observed since 2016, along with the increased use of new oral anticoagulants compared to vitamin K antagonists. The final model indicated that the increase in oral anticoagulation use between 2012 and 2018, in mainland Portugal, was associated with a decrease in the number of episodes of stroke associated with atrial fibrillation. It was estimated that the shift in the type of anticoagulation used, between 2016 and 2018, was associated with a reduction of 833 episodes of stroke in patients with atrial fibrillation (4.2%). The use of oral anticoagulation was associated with a reduced incidence of stroke in patients with atrial fibrillation in mainland Portugal. This reduction was more relevant in the period between 2016 and 2018, and is probably related with the introduction of the novel oral anticoagulants.

A personalised approach to the choice of oral anticoagulants in elderly and senile patients with atrial fibrillation

Introduction. In recent years, data have been accumulated regarding possible associations between cognitive impairment and atrial fibrillation. The results of retrospective and prospective studies confirm that anticoagulant therapy in patients with AF can reduce the risk of cognitive impairment and dementia.Objective. To study the individual characteristics of elderly and senile patients with atrial fibrillation, influencing the choice of anticoagulant therapy, with a view to its subsequent optimization.Materials and methods. The study included 159 patients with atrial fibrillation of non-valvular genesis aged over 60 years. 4 groups of patients were formed. The largest number of patients received rivaroxaban and warfarin (36.4% and 34.6%, respectively). 26 (16.3%) patients were treated with dabigatran, 20 (12.6%) patients with apixaban. The risk of thromboembolic complications was assessed on the CHA2DS2-VASc scale. The HAS-BLED scale was used to assess the risk of bleeding. A pharmacogenetic study (carriage of polymorphic alleles of the CYP2C9 and VCORC1 genes) was conducted in 138 patients. Cognitive impairment was assessed by a Mini-Cog test and a battery of frontal tests.Results. Taking oral anticoagulants reduces the risk of stroke and dementia in patients; the presence of cognitive impairment, in turn, significantly reduces the patient’s adherence to therapy and reduces the effectiveness of therapy. Patients’ adherence to therapy was significantly lower by 10–20% in patients with cognitive impairment according to the Mini-Cog test and a battery of frontal tests. In the absence of pronounced cognitive impairment (higher adherence to treatment) and availability and willingness to control INR, warfarin remains the drug of choice in patients with renal insufficiency.Conclusions. A number of problems with the use of oral anticoagulants in elderly patients with atrial fibrillation have been identified. The ease of use of new oral anticoagulants, the absence of the need to select doses and monitor therapy is an important factor when choosing a drug.

New Oral Anticoagulants Open New Horizons for Cancer Patients with Venous Thromboembolism.

Venous thromboembolism (VTE) is associated with increased morbidity and mortality, decreased quality of life, and higher economic burden in patients with cancer. Currently, the treatment of VTE in patients with cancer is particularly challenging. For many years, low molecular weight heparin (LMWHs) has been the standard for the treatment of cancer-associated VTE. Recently, the introduction of new oral anticoagulants (NOACs) may offer an oral anticoagulant option for some patients with cancer-associated thrombosis (CAT) as a growing body of literature supports the use of NOACs in the setting of CAT. With the use of NOAC as a new option in the management of CAT, clinicians now face several choices for the individual cancer patient with VTE. We need a more in-depth understanding of the drug properties, efficacy and safety, economic analysis that allows us to choose the most appropriate treatment for each patient. In the review, we will present an overview of CAT management, discuss the available evidence, economic costs for NOACs in the treatment of CAT, and seek to provide the best range of treatments for cancer patients.

MO143: Dynamics of Renal Function during Anticoagulant Therapy in Stage 4 CKD and AF

Abstract BACKGROUND AND AIMS Atrial fibrillation (AF) significantly increases the risk of developing end-stage chronic kidney disease (CKD). It should also be borne in mind that as kidney function deteriorates the risk of AF progression and its complications increases. Various studies have shown the superiority of new oral anticoagulants (NOACs) over vitamin K antagonists (VKAs) in CKD stages 1–3. Patients with stage 4–5 CKD were not included in many of these studies because of the high risk of impaired renal function and various complications. Clinical data on the use of NOACs in this group of patients are limited, which determines the relevance of conducting studies in comparison with VKA. The aim of our study was to monitor the dynamics of renal function in patients with stage 4 CKD and AF on the background of anticoagulant therapy. METHOD The studies included 106 patients, of which 73 patients took rivaroxaban (at a dose of 15 mg/day) and 33 patients took warfarin (the dose was selected individually according to INR). The duration of the study is 18 months. The level of creatinine in the blood plasma was determined in all patients. The calculation of the glomerular filtration rate (GFR) was carried out according to the CKD-EPI formula, as well as creatinine clearance (CC) according to the Cockcroft-Golt formula. To assess the dynamics of changes in the level of creatinine and GFR over time, linear mixed models were built for each group. The time in months and the anticoagulant (rivaroxaban or warfarin) taken were selected as fixed effects. RESULTS During the study, there was a significant improvement in the dynamics of creatinine and GFR in the rivaroxaban group when compared with the warfarin group. When considering a linear model of creatinine level, the interaction coefficient time * drug is –1.3, GFR according to the CKD-EPI formula 0.21, CC 0.20 (P < .001). In patients receiving rivaroxaban, there was an increase in GFR and a decrease in creatinine levels, whereas patients taking warfarin showed the opposite dynamics of indicators of renal function. The dynamics of creatinine levels within 18 months in the rivaroxaban group decreased from 195 to 180 μmol/L, and in the warfarin group increased from 203 to 221 μmol/L on average (P < .001). Dynamics of GFR according to the CKD-EPI formula in the NOACs group on average from 23.0 to 25.5 mL/min/1.73 m2 and CC according to the Cockcroft-Golt formula 27.0 to 31.0 mL/min. These indicators in the VKA group on average were equal from 22.0 to 20.0 mL/min/1.73 m2 (GFR), and 25.0 to 23.0 mL/min (CC). It should be noted that during the study, the transition from the fourth stage of CKD to the third stage was recorded in 32 (43.8%) patients in the rivaroxaban group and in 11 (33.3%) patients in the warfarin group (P = .26). However, there was also a transition of four patients (3.8%) to the fifth stage. CONCLUSION Taking rivaroxaban was accompanied by an improvement in renal function, which may indicate a nephroprotective effect of the drug. For the assessment of renal function in patients with AF, the use of the CKD-EPI formula seems to be preferred. These studies indicate a favorable safety profile for rivaroxaban versus warfarin in patients with stage 4 CKD and AF.

MO182: Safety Analysis of Anticoagulant Therapy in Stage 4 CKD in Combination with AF

Abstract BACKGROUND AND AIMS A renocardial comorbid condition with a combination of chronic kidney disease (CKD) and atrial fibrillation (AF) increases the risk of thromboembolic complications (TEC) and hemorrhagic events. As kidney function worsens, this risk only increases. Anticoagulant therapy is the standard for prevention of acute cerebrovascular accident (ACVA) in AF. Clinical data on the use of new oral anticoagulants (NOACs) in patients with advanced CKD and AF are very limited, which indicates the relevance of research. Analysis of safety and efficacy indicators of rivaroxaban in patients with stage 4 CKD in combination with AF. METHOD The study included 106 patients with a glomerular filtration rate (GFR) of 15–29 mL/min/1.73 m2 and AF. A total of 73 patients took rivaroxaban at a dose of 15 mg/day and 33 patients took warfarin, the dose of which was individually adjusted according to INR values. The average follow-up period was 18 months. Thromboembolic complications were the primary endpoint. The secondary endpoint is the development of haemorrhagic events (major and minor bleeding). RESULTS In the rivaroxaban group, the mean CHA2DS2 VASc score was 4.9, the HAS BLED score was 3.2, and in the warfarin group, 4.5 and 3.1, respectively. The incidence of stroke in the rivaroxaban group was observed in one patient (1.37%), and in the warfarin group in two patients (6.06%). The results of the study on the primary endpoint indicate that the indicators in both groups did not differ significantly (P = .24). The incidence of haemorrhagic events such as minor bleeding in the rivaroxaban group on the BARC scale was n = 31 (42.5%), and n = 24 (72.7%) in the warfarin group (P < .01). This indicator on the ISTH scale is n = 27 (36.9%) and n = 21 (63.6%), respectively. Major bleeding was observed in the rivaroxaban group n = 2 (2.74%), and in the warfarin group n = 2 (6.06%) on the BARC and ISTH scales (P = .31). Heamorrhagic events were significantly more frequent in the warfarin group compared with the rivaroxaban group. CONCLUSION The data obtained from this study indicate a favourable safety profile of NOAC (rivaroxaban) compared with a vitamin K antagonist in patients with stage 4 CKD in combination with AF.

POS-246 EVALUATION OF THE USE OF RIVAROXABAN IN PATIENTS WITH STAGE 4 CKD IN AF

Anticoagulant therapy is the standard for the prevention of thromboembolic complications (TEC) and, first of all, acute cerebrovascular accident (ACVA) in atrial fibrillation (AF). The combination of advanced chronic kidney disease (CKD) and AF leads to an even greater increase in the risk of TEO, but is also a risk factor for various bleeding. Clinical data on the use of new oral anticoagulants (NOACs) in this group of patients are limited, which determines the relevance of studies in comparison with vitamin K antagonists.

New Oral Anticoagulants for Venous Thromboembolism Prophylaxis in Total Hip and Knee Arthroplasty: A Systematic Review and Network Meta-Analysis.

Background: There is controversy over whether use of new oral anticoagulants (NOACs) associates with increased hemorrhage risk compared with non-NOAC. Meanwhile, determining which NOAC to use remains unclear. We aimed to summarize the evidence about NOACs in venous thromboembolism (VTE) prevention for patients with total hip and knee arthroplasty (THA and TKA). Methods: We searched RCTs assessing NOACs for VTE prophylaxis in adults undergoing THA and TKA in Medline, Embase, and Cochrane up to May 2021. Primary outcomes were VTE [included deep vein thrombosis (DVT) and pulmonary embolism (PE)], major VTE, and major bleeding. The rank probabilities of each treatment were summarized by the surface under the cumulative ranking curve area (SUCRA). Results: 25 RCTs with 42,994 patients were included. Compared with non-NOAC, NOACs were associated with a decreased risk of VTE (RR 0.68; 95% CI 0.55–0.84) and major VTE (RR = 0.52; 95% CI 0.35–0.76). Additionally, rivaroxaban, apixaban, and edoxaban but not dabigatran and betrixaban, did confer a higher efficacy compared with non-NOAC. None of the individual NOACs increased the risk of bleeding, while apixaban and betrixaban were even associated with a decreased risk of bleeding. In the comparison of different NOACs, rivaroxaban was associated with the greatest benefits in VTE (SUCRA = 79.6), DVT (SUCRA = 88.8), and major VTE (SUCRA = 89.9) prevention. Furthermore, subgroup analysis confirmed that NOACs associated with a higher efficacy tendency in patients with follow-up duration <60 days than follow-up duration ≥60 days. Conclusion: Evidence suggests that NOACs exert more benefits on VTE prophylaxis, and none of the individual NOACs increased hemorrhage compared with non-NOAC. Among various NOACs, rivaroxaban is recommended in patients with lower bleeding risk, and apixaban is recommended in patients with higher bleeding risk. Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42021266890].

Factors related to patient adherence to the use of new oral anticoagulants.

To characterize the self-reported adherence of patients with cardiovascular diseases to the use of new oral anticoagulants and to identify factors related to adherence to these drugs. This is a descriptive, correlational, and cross-sectional study, carried out with outpatients. The collection of sociodemographic, clinical, and adherence data, through the Measurement of Adherence to Treatments, was made through telephone calls. Descriptive, correlation, and multiple linear regression analyses were used. A total of 120 patients using new anticoagulants for 32.3 months, on average, participated in the study. More than half of the sample consisted of women, who were professionally inactive, with a mean age of 70.1 years and a mean family income of 6.7 minimum wages. The mean adherence score was 5.7, in a possible range between 1 and 6, indicating medication adherence. Inactive employment status, female sex, higher family income, and follow-up at a public outpatient clinic were related to greater adherence to these medications. The patients showed high adherence to new anticoagulants. Employment status, sex, family income, and type of outpatient follow-up were related to medication adherence, and should be considered in the design of interventions for this public.

Гострий тромбоз стента при інфаркті міокарда, ускладненому кардіогенним шоком, за наявності цукрового діабету 2-го типу

Актуальність. Гострий тромбоз стента (ТС) є нечастим, але грізним ускладненням при стентуванні вінцевих артерій. Він виникає під час черезшкірних коронарних втручань або впродовж 24 годин після цієї процедури. Мета дослідження: з’ясувати причини та проаналізувати фактори, що призвели до гострого ТС при гострому коронарному синдромі і цукровому діабеті (ЦД) 2-го типу, для уникнення подібних ускладнень. Матеріали та методи. Обстежено 119 пацієнтів із гострим інфарктом міокарда з елевацією сегмента ST, які лікувалися в інфарктному відділенні комунального некомерційного підприємства «Клінічна лікарня швидкої медичної допомоги м. Львова». Усім пацієнтам проводили коронарографію та стентування вінцевих артерій, ультраструктурні дослідження тромбоцитів венозної крові за допомогою електронної мікроскопії. Результати. Пацієнти із ЦД 2-го типу мають вищий кардіоваскулярний ризик розвитку серцево-судинних ускладнень, що пов’язано з ендотеліальною дисфункцією, схильністю до гіперкоагуляції і, як наслідок, тенденцією до вазоконстрикції, запальних реакцій та порушень гемостазу. У цієї категорії пацієнтів спостерігається підвищена адгезивність тромбоцитів і збільшена концентрація тканинного активатора плазміногену. В експрес-некроптатах і періопераційних біоптатах міокарда пацієнтів із ЦД нами виявлено домінування процесів гіперкоагуляції в мікросудинах міокарда в результаті активності системи згортання крові за відсутності безпосередньої участі тромбоцитів, оскільки частина з них була кальцифікована (осміофільні) і мала знижену функціональну здатність, в результаті чого відмічається резистентність до аспірину. В осіб із ЦД 2-го типу виникає зазвичай тяжкий і більш генералізований коронаросклероз, що призводить до погіршення перебігу гострого коронарного синдрому і частішого виникнення ТС, що робить доцільним додаткове призначення ривароксабану цій категорії пацієнтів. Висновки. Враховуючи виявлені нами ознаки зниженої реактивності тромбоцитів і домінування активації системи згортання крові у хворих на ЦД і з підвищеним ризиком коронаротромбозу, вважаємо, що застосування нових пероральних антикоагулянтів є актуальним і заслуговує подальших досліджень.

175Bleeding and cardiovascular risk of New Oral Anti-Coagulants (NOACs) versus warfarin in type 2 diabetes

Abstract Background New oral anticoagulants (NOACs) (vs warfarin) in the general population are associated with 34% less major bleeding events. We compared the risk of bleeding and cardiovascular disease (CVD) events between NOACs and warfarin in people with type 2 diabetes (T2DM). Methods Incident NOAC users (cases) and matched controls (incident warfarin users) with T2DM were identified from within 40 UK general practice records (1/4/2017-31/3/2018). Coarsened Exact Matching restricted the comparison to areas of sufficient overlap in characteristics (i-iv) and missingness. Entropy Balancing sequentially balanced NOAC and warfarin users on their distribution of (i) age, sex, general practice, first anticoagulant prescription year, diabetes duration, (ii) body mass index, systolic blood pressure, total cholesterol, HbA1c, (iii) bleeding/CVD history, (iv) treatment (Antiplatelet, Corticosteroids, statins, anti-hypertensives, anti-diabetes treatment number). Continuous covariates were balanced for mean, variance, and skewness. Pre-processing/balancing occurred without reference to outcomes. Multivariable logistic regression modelling estimated bleeding and CVD relative risks (RRs: incident non-elective hospitalisation within 12 months since first anticoagulant prescription), identified from linked hospitalisation data (Secondary Uses Service dataset), using entropy balancing weights from steps i-iv. Results The twelve month RRs of bleeding with NOAC (n = 967) vs matched/balanced warfarin (n = 911) were 0.94(0.62-1.45), 0.95(0.62-1.46), 0.98(0.65-1.48) and 0.98(0.67-1.43) through steps i-iv. CVD RR was increased with NOAC treatment through steps i-iv: 1.15(1.00-1.31), 1.22(1.06-1.39), 1.34(1.13-1.60) and 1.43(1.20-1.70). Conclusion Among T2DM patients, risk of bleeding among NOAC and warfarin incident users was similar. However, NOAC use significantly increased the risk of CVD events. Further external replication studies are warranted.

The use of new oral anticoagulants in geriatric patients: A survey study for physicians.

The use of new oral anticoagulants (NOACs) for the treatment of thromboembolic diseases is becoming more widespread. The present study brings together the opinions and daily routine clinical practices of physicians regarding the use of NOACs in the geriatric age group for the treatment of venous thromboembolic diseases. The study accessed 274 physicians (197 attending, 70 resident and seven primary care physicians) with various specialties and academic positions through face-to-face interviews or e-mails, and asked them to complete a questionnaire form prepared for NOAC use on a voluntary basis between 1 May and 31 December 2019. It was found that physicians preferred NOACs mostly for patients contraindicated for the regular use of low-molecular-weight heparins and warfarin (n: 264, 96%), and with an unbalanced INR level (n: 230, 87%). The use of NOACs was found to be higher in the geriatric age group than other anticoagulants due to the easy dose adjustment, the extended monitoring intervals and the low risk of bleeding. Among the physicians, neither the specialty nor a higher number of occupational working years affected the preference for NOACs or other anticoagulants. Our study has demonstrated that physicians consider NOACs to be a good treatment option in terms of efficacy and reliability for the treatment of thromboembolic diseases in the geriatric age group, who may have treatment compliance difficulties. It was found also that they plan treatment considering the benefit-to-harm ratio and the bleeding-ischemic event balance.

Main factors of adherence to new oral anticoagulants and its dynamics in outpatients with nonvalvular atrial fibrillation: results of the ANTEY study

Aim. To assess adherence to new oral anticoagulants (NOAC) or warfarin therapy and to study the factors influencing adherence in nonvalvular atrial fibrillation (AF) patients on different stages of treatment within the prospective outpatient registry of patients with cardiovascular diseases. Material and methods . The study included 201 patients with nonvalvular AF (males, 118 (58,7%)) from the outpatient registry PROFILE). Mean age was 71,1 ±8,7 years. Study protocol consisted of the inclusion visit (V0), 6-month follow-up visit (V1) and phone contact 1 year after V0 (PC). In V0, all patients were prescribed one of the NOACs. At V1 doctors could recommend warfarin or another NOAC to patients, who have refused taking prescribed NOAC. Medical adherence was determined using the of the National society of evidence-based pharmacotherapy (NSEPh) adherence scale. NSEPh adherence scale allows to grade patients’ adherence to treatment into 4 categories: 1) completely adherent, 2) partially adherent, 3) completely non-adherent, 4) partially non-adherent. Dichotomous grading into adherent (completely adherent) and non-adherent (rest of patients) was also used. Results. Out of 201 included patients, 200 came to V1 (1 patient died). PC was successful in 197 patients (3 patients died). According to NSEPh adherence scale, 155 (77,5%) patients at V1 were completely adherent, 5 (2,5%) — partially adherent, 7 (3,5%) — partially non-adherent, 33 (16,5%) — completely non-adherent. By the PC, 158 (80,2%) patients were completely adherent to the OAC therapy, 6 (3,0%) — partially adherent, 28 (14,2%) — partially non-adherent, 15 (7,6%) — completely non-adherent. At all stages of treatment, the following factors of good adherence remained significant: never-smoking, prior NOAC use, negative history of any treatment-related adverse effects (AEs). Patients with comorbidities and a history of bleeding during OAC therapy were more likely to discontinue initial scheme and violate treatment regimen (p&lt;0,05). Symptomatic course of AF increased adherence by 2,4 times ( р =0,02). According to the questionnaire, the leading reasons for refusing NOAC therapy were the high cost of drugs, the fear of AE and doubts about the need for treatment. The main factors leading to discontinuation of NOAC/OAC treatment were bleeding and the cancellation (often unreasonable) of these medications by other doctors. Conclusion. The results of ANTEY study confirm that factors influencing adherence to NOAC may vary during different phases of treatment. The main reasons that prevent NOAC therapy initiation are the high cost of these drugs, fear of AE and doubts about the need for such treatment. Significant factors of discontinuation were AEs and cancellation of NOAC therapy by doctors from other medical institutions. Factors that positively affect both initiation and long-term use of the drug are never-smoking, prior NOAC use, negative history of any treatment-related AEs.

Experience of using idarucizumab, specific antagonist of dabigatran, in Russia

Atrial fibrillation (AF) is the most common type of arrhythmias in clinical practice. It has been proven that the presence of AF increases the risk of stroke by five times relative to the population of people without AF. One of the important issues in the management of patients with atrial fibrillation is the management of the risk of thromboembolic complications, namely the optimal selection of anticoagulant therapy. Most oral anticoagulants (dabigatran, apixaban, rivaroxaban) are the most effective and safest drug in patients with nonvalvular AF compared to warfarin. However, even with the use of new oral anticoagulants, there is a proven risk of bleeding, which ranges from minor to life-threatening. Currently, there are approved non-specific strategies for reversing and replenishing clotting factors associated with the use of oral anticoagulants, with certain indications in a patient with severe or life-threatening bleeding, emergency surgery, or before thrombolytic therapy. Over the past few years, specific oral anticoagulants antagonists have been actively studied. Of the specific oral anticoagulants antagonists, only idarucizumab has been approved in Russia (registration of the drug in Russia since September 2018), which makes it safer to use dabigatran in real clinical practice. The article presents clinical cases illustrating the effectiveness of the use of a specific antagonist dabigatran etexilate (idarucizumab) in patients with nonvalvular atrial fibrillation. Clinical examples illustrate the difficulties of managing patients with atrial fibrillation and hemorrhagic complications while taking oral anticoagulants.

Safety of early anticoagulation in patients treated with urgent reperfusion for acute ischemic stroke related to non-valvular atrial fibrillation

Abstract Background The optimal timing for starting anticoagulation after an acute ischemic stroke related to non-valvular atrial fibrillation (AF) remains a challenge, especially in patients treated with systemic thrombolysis or mechanical thrombectomy. Purpose We aimed to assess the rates of early recurrence and major bleeding in patients with acute ischemic stroke and AF treated with thrombolytic therapy and/or thrombectomy who received oral anticoagulants for secondary prevention. Methods We combined the dataset of the RAF and the RAF-NOACs studies, which were prospective observational studies carried out from January 2012 to March 2014 and April 2014 to June 2016, respectively. We included consecutive patients with acute ischemic stroke and AF treated with either vitamin K antagonists (VKAs) or new oral anticoagulants (NOACs). Primary outcome was the composite of stroke, transient ischemic attack, symptomatic systemic embolism, symptomatic cerebral bleeding, and major extracerebral bleeding within 90 days from the inclusion. Results A total of 2,159 patients were included in the RAF and RAF-NOACs trials, of which 564 patients (26%) were treated with urgent reperfusion therapy. After acute stroke, 505 (90%) patients treated with reperfusion and 1,287 out of the 1,595 (81%) patients not treated with reperfusion started oral anticoagulation. Timing of starting oral anticoagulation was similar in reperfusion-treated and untreated patients (13.5±23.3 vs 12.3±18.3 days, respectively, p=0.287). At 90 days, the composite rate of recurrence and major bleeding occurred in 37 (7%) of patients treated with reperfusion treatment and in 139 (9%) of untreated patients (p=0.127). Twenty-four (4%) reperfusion-treated patients and 82 (5%) untreated patients had early recurrence while major bleeding occurred in 13 (2%) treated and in 64 (4%) untreated patients, respectively. Seven patients in the untreated group experienced both an ischemic and hemorrhagic event. Figure 1 shows the risk of early recurrence and major bleeding over time in patients treated and not treated with reperfusion treatments. The use of NOACs was associated with a favorable rate of the primary outcome compared to VKAs (Odd ratio 0.4, 95% Confidence Interval 0.3–0.7). Conclusions Reperfusion treatment did not influence the risk of early recurrence and major bleeding in patients with AF-related acute ischemic stroke who started anticoagulant treatment. Figure 1 Funding Acknowledgement Type of funding source: None