Non-vitamin K-dependent Oral Anticoagulants Research Articles

Updated review on malignancy-associated venous thromboembolism: Pathogenesis and comparison between various therapeutic modalities

Venous thromboembolism (VTE) is one of the life-threatening complications in cancer patients, the incidence of which is affected by the patient and malignancy-related variables. Location, type, therapeutic route, stage, grade, and non-supportive treatment of the cancer are the most important VTE risk factors. Patient age, ethnicity, and concomitant genetic or acquired comorbidities or thrombophilias are known risk factors for VTE in cancer. All high-risk cancer patients admitted to hospitals or treated as outpatients should receive VTE prophylaxis. Low molecular weight heparin is the main treatment for active malignant VTE. Vitamin K antagonists and non-Vitamin K-dependent oral anticoagulants are used in stable, non-bleeding cancer patients. Anticoagulation should be continued until the cancer is treated or at least controlled. Over the past two decades, randomized clinical and observational trials have improved the pathogenesis and therapeutic knowledge of VTE, but many challenges remain. The lack of an optimal primary prophylaxis method for inpatients and outpatients in oncology and the care of cancer-associated VTE in standard and high-bleeding risk groups are examples for which more clinical research on cancer-associated thrombosis is necessary to address these issues. In this review, we describe the pathogenesis, factors that increase the risk of VTE, and the comparison between the effectiveness of available anticoagulants in the treatment and prevention of VTE in cancer patients.

Study Design of a Brazilian Observational Study of Edoxaban in Patients with Atrial Fibrillation (EdoBRA).

Clinical trials showed the safety of Edoxaban, a non-vitamin K-dependent oral anticoagulant (NOAC), and its efficacy to prevent stroke and systemic embolism in non-valvular atrial fibrillation (NVAF) patients and also to prevent and treat venous thromboembolism. However, additional research is needed to evaluate the safety and effectiveness of Edoxaban in a real-world scenario in the Brazilian population. In order to understand the risks and benefits of Edoxaban use in routine clinical settings, the EdoBRA study is being conducted to gain insight into the safety and effectiveness of Edoxaban use in non-preselected patients with NVAF in Brazil. The EdoBRA study is a multicenter, prospective, observational study conducted in 36 sites in Brazil. NVAF patients ≥ 18 years treated with commercially available Edoxaban who initiated treatment for at least 14 days and no longer than 90 days prior to enrollment, and who are not simultaneously participating in any interventional study are eligible for this study. Seven hundred patients are planned to be enrolled and one-year of follow up, with data collections expected at baseline and 3, 6, and 12 months after the study enrollment. The primary safety objective is ISTH Clinically Relevant Bleeding, and the secondary effectiveness objective focuses on relevant cardiovascular outcomes related to NVAF. EdoBRA observational study will generate relevant additional information about NOAC Edoxaban on various aspects of patient management in routine care, such as its safety and effectiveness profile in patients with NVAF in Brazil.

Primary Care in Management of Pulmonary Embolism in Prolonged Recumbences

A frequent and possibly fatal kind of venous thromboembolic illness is pulmonary embolism (PE). It is a significant issue for public health. A typical diagnosis as a primary care in an emergency room is pulmonary embolism (PE). Additionally, it makes up a sizable portion of the patients admitted to hospital wards. In selected low-risk individuals with acute PE, there is mounting evidence that outpatient therapy, or treatment without hospitalization, is practical, safe, and efficient. PE patients may be risk-classified and given an early release from the emergency department. As a result, there are more hospital beds available for other patients, which lowers treatment expenses for the healthcare system. There is growing support for the outpatient care of low-risk, hemo-dynamically stable patients with acute symptomatic pulmonary embolism (PE). There is assistance in identifying patients who are eligible for outpatient (primary) care. This move has been made easier by the accessibility and simplicity of direct oral anticoagulants. Acute PE is currently mostly treated with direct, non-vitamin K-dependent oral anticoagulants. In comparison to vitamin K antagonists, they have been demonstrated to simplify initial and prolonged anticoagulation regimes while lowering the risk of bleeding. In this consensus practice document, we present a thorough analysis of primary care in the diagnosis, treatment, and follow-up of acute PE.

Periinterventional Management of Edoxaban in Major Procedures: Results from the DRESDEN NOAC REGISTRY.

Background Edoxaban is a non-vitamin K dependent oral anticoagulant (NOAC) licensed for venous thromboembolism (VTE) treatment or stroke prevention in atrial fibrillation. Major surgical procedures are not uncommon in anticoagulated patients but data on perioperative edoxaban management are scarce. Patients and Methods Using data from the prospective DRESDEN NOAC REGISTRY, we extracted data on major surgical procedures in edoxaban patients. Periinterventional edoxaban management patterns and rates of outcome events were evaluated until day 30 after procedure. Results Between 2011 and 2021, 3,448 procedures were identified in edoxaban patients, including 287 (8.3%) major procedures. A scheduled interruption of edoxaban was observed in 284/287 major procedures (99%) with a total median edoxaban interruption time of 11.0 days (25-75th percentile: 5.0-18.0 days). Heparin bridging was documented in 183 procedures (46 prophylactic dosages, 111 intermediate and 26 therapeutic dosages). Overall, 7 (2.4%; 95% CI: 1.2-4.9%) major cardiovascular events (5 VTE, 2 arterial thromboembolic events) and 38 major bleedings (13.2%; 95% CI: 9.8-17.7%) were observed and 6 patients died (2.1%; 95% CI: 1.0-4.5%). Rates of major cardiovascular events with or without heparin bridging were comparable (4/137; 2.9%; 95% CI: 1.1-7.3% vs. 3/82; 3.7%; 95% CI: 1.3-10.2%). Major bleedings occurred numerically more frequent in patients receiving heparin bridging (23/137; 16.8%; 95% CI: 11.5-23.9%) versus procedures without heparin bridging (9/82; 11.0%; 95% CI: 5.9-19.6%). Conclusion Within the limitations of our study design, real-world periprocedural edoxaban management seems effective and safe. Use of heparin bridging seems to have limited effects on reducing vascular events but may increase bleeding risk.

Better Survival in Morbidly Obese Patients with Atrial Fibrillation Treated with Non-vitamin K-dependent Oral Anticoagulants.

The efficacy and safety of non-vitamin K-dependent anticoagulants (NOAC) are not well investigated in the obese population, and fixed dosing could lead to under-anticoagulation. Our objective was to evaluate the effect of obesity on anticoagulation outcomes and survival in non-valvular atrial fibrillation (AF) patients. We enrolled 755 patients who required anticoagulation for AF from 2015 to 2016. We grouped the patients into four groups. Group 1 (n = 297) included patients with BMI< 40 kg/m2 treated with NOACs, Group 2 (n = 358) included patients on warfarin with BMI< 40 kg/m2, Group 3 (n = 57) had patients on NOACs with BMI≥ 40 kg/m2 and Group 4 (n = 43) included patients on warfarin and BMI≥ 40 kg/m2. Study outcomes were the composite endpoint of stroke, bleeding, and survival. Competing risk regression showed that stroke and bleeding were not affected by obesity or treatment (SHR: 1.09 (95% CI: 0.79-1.51); P = 0.62). Older age was the predictor of stroke/bleeding (HR:1.03 (95% CI:1.01-1.06); P = 0.02). Predictors of mortality were heart failure (HR:2.23 (95% CI:1.25-3.97); P = 0.007), lower creatinine clearance (HR: 0.98 (95% CI:0.97-0.98): P < 0.001), non-obese patients on warfarin (HR:3.51 (95%CI:1.6-7.7): P = 0.002) and obese patients on warfarin (HR: 6.7 (95% CI:2.51-17.92); P < 0.001). NOACs could have a similar risk profile to warfarin in obese and non-obese patients with non-valvular AF but could have better survival. Larger randomized trials are recommended.

Modern anticoagulation with factor Xa inhibitors in oncology: is the gastrointestinal bleeding rate (also) decisive?

The increased risk of thrombosis and bleeding with an active tumor disease is known as the so-called "thrombo-hemorrhagic syndrome", which places high demands on anticoagulation. There are currently 4 randomized, prospective studies on the use of new, non-vitamin K dependent oral anticoagulants (NOAC) for the treatment of venous thromboembolism (VTE) that have occurred in oncology. The FXa inhibitors rivaroxaban, edoxaban and twice apixaban were each used in individual studies versus the standard therapeutic agent dalteparin. Since there is no direct head-to-head comparison of the FXa inhibitors mentioned within a study, the largest study - always compared to dalteparin - was evaluated for each NOAC. The studies were analyzed with regard to their effectiveness, safety, fatal bleeding rates, the risk of gastrointestinal bleeding (GIB) and other differences using descriptive statistics. With dalteparin, the mean VTE recurrence rate was approximately 9% over a 6-month treatment period. All three FXa inhibitors were not inferior to dalteparin in terms of potency. The VTE recurrence rate was - 2.3% lower in edoxaban and apixaban-treated patients and - 5.0% in rivaroxaban-treated patients. In terms of safety, there was an increased rate of severe bleeding (both + 2.4%) for rivaroxaban and edoxaban compared to dalteparin; in particular, the number of GIBs was significantly increased. In contrast, the number of severe bleeding was not increased for apixaban, as was the case for various bleeding types including GIB. In the Apixaban study, the overall rate of severe GIB, which accounted for about 50% of all severe bleeding, and that of clinically relevant non-severe bleeding, were the lowest. The FXa inhibitors are not inferior to the standard therapy with dalteparin in the VTE recurrence rate in oncological patients. The GIB rate appears to be an important predictive factor for the safety of this group of substances, so that tumor location, gastrointestinal risk factors and other individual criteria should be given greater consideration in future therapy decisions for or against an FXa inhibitor.

Changes in Prescription Patterns of Oral Anticoagulants in Family Practices after Marketing Approval of Direct Oral Anticoagulants

Since 2011, non-vitamin-K-dependent oral anticoagulants (NOAC) have extended the spectrum of anticoagulation therapy. Initially, the approval of NOAC was limited to the prophylaxis of postoperative thrombosis, but in the course of time the spectrum was extended to the therapy of thrombosis and embolism as well as anticoagulation in non-valvular atrial fibrillation. The study was designed to examine how the approval of NOAC had affected the prescribing behaviour of general practitioners in the first years of their approval. In a retrospective longitudinal study, the prescriptions of anticoagulants between 2012 and 2017 were analysed in 3 general practitioners' practices in the Bonn area. The study included all patients for whom at least one prescription from a NOAC or a vitamin K antagonist (VKA) was documented in the administrative system of the practices during this period. A total of n=579 patient files were evaluated (47% female; median age 75 years). Of these, 47% received a VKA, and 40% a NOAC (59% rivaroxaban, 29% apixaban, 9% dabigatran and 3% edoxaban). During the period under examination, the share of VKA prescriptions decreased from 45% to 14% and the share of NOAC increased from 28% to 87%. Anti-coagulation was changed in 12%. The most frequent change was from a VKA to a NOAC (70%). After marketing approval, the use of NOAC in the initial prescriptions increased steadily. This trend can also be seen in other European studies. VKA are mainly prescribed to patients with stable oral anticoagulation. As recommended in the guidelines, anticoagulation is changed mainly when problems occur during therapy. If the trend in the prescription of anticoagulants continues, in the medium term, VKA will only be prescribed for patients who have been stable for many years and for patients with artificial heart valves.

Resolution of left atrial appendage thrombi: No difference between phenprocoumon and non-vitamin K-dependent oral antagonists.

BackgroundAtrial fibrillation is the most important risk factor for left atrial appendage (LAA) thrombi, a potentially life‐threatening condition. Thrombus resolution may prevent embolic events and allow rhythm‐control strategies, which have been shown to reduce cardiovascular complications.HypothesisThere is no significant difference between phenprocoumon and non‐Vitamin K‐dependent oral anticoagulants (NOACs) in the resolution of LAA‐thrombi in a real‐world setting.MethodsConsecutive patients with LAA‐thrombi from June 2013 to June 2017 were included in an observational single‐center analysis. The primary endpoint was defined as the resolution of the thrombus. The observational period was 1 year. Resolutions rates in patients on phenprocoumon or NOACs were compared and the time to resolution was analyzed.ResultsWe identified 114 patients with LAA‐thrombi. There was no significant difference in the efficacy of resolution between phenprocoumon and NOACs (p = .499) at the time of first control which took place after a mean of 58 ± 42.2 (median 48) days. At first control most thrombi were dissolved (74.6%). The analysis after set‐time intervals revealed a resolution rate of 2/3 of LAA‐thrombi after 8–10 weeks in the phenprocoumon and NOAC groups. After 12 weeks a higher number of thrombi had resolved in the presence of NOAC (89.3%) whereas in the presence of phenprocoumon 68.3% had resolved (p = .046).ConclusionIn this large observational study NOACs were found to be potent drugs for the resolution of LAA‐thrombi. In addition, the resolution of LAA‐thrombi was found to be faster in the presence of NOAC as compared to phenprocoumon.

Safety and effectiveness of oral anticoagulation in patients with atrial fibrillation and renal insufficiency - a real-world perspective

Non-vitamin-K dependent oral anti-coagulants (NOAC) are the current therapeutic standard for preventing strokes in patients with atrial fibrillation (AF) and should be preferred over vitamin K antagonists (VKA) in this indication. This recommendation applies also to patients with VHF and concomitant chronic kidney disease (CKD). Real World Evidence (RWE), i. e., structured data from clinical practice, extends and confirms the clinical evidence generated in more formalized clinical trials with NOAC and VKA. In addition, RWE in respect to the indication showed that the superiority of NOAC versus the VKA warfarin can also be extrapolated to phenprocoumon, the commonly used VKA in Germany. Furthermore, data include evidence that the typical progression of CKD appears to be less pronounced in individuals treated with NOAC compared to those treated with VKA.

Influence of rivaroxaban compared to vitamin K antagonist treatment upon development of cardiovascular calcification in patients with atrial fibrillation and/or pulmonary embolism.

BackgroundVitamin K antagonists (VKA) such as warfarin or phenprocoumon have been the mainstay of therapy for long‐term oral anticoagulant therapy (OAT) in patients with atrial fibrillation or with pulmonary embolism. Due to interferences with matrix Gla‐protein, an important vitamin K‐dependent local calcification inhibitor in cardiovascular structures, VKA antagonists stimulate cardiovascular calcification (CVC). In contrast, rivaroxaban, a nonvitamin K‐dependent oral anticoagulant (NOAC), should be neutral in terms of CVC. We seek to investigate these potential differences in CVC development between VKA versus NOACs in a randomized controlled trial (RCT).MethodsThe influence of rivaroxaban compared to vitamin K antagonist treatment upon development of cardiovascular calcification in patients with atrial fibrillation and/or pulmonary embolism trial (NCT02066662) is a multicenter, prospective RCT with a two‐arm, open‐label study design. The primary endpoint is the progression of coronary and aortic valve calcification (quantified as calcification volume score) as assessed by cardiac computed tomography (CT) at 24 months in patients either treated by rivaroxaban or VKA. A total of 192 patients were randomized in a 1:1 fashion. The main inclusion criteria were the presence of atrial fibrillation and/or pulmonary embolism with the indication for OAT and pre‐existent coronary calcification. The development of CVC will be assessed by follow‐up CT at 12 and 24 months.ResultsIn total 192 patients (median age 70, 72% male) were enrolled over a period of 5 years and followed up for 2 years.

Use of Non-Vitamin K Dependent Oral Anticoagulant in Ischemic Stroke

Atrial fibrillation (AF) is associated with an increased incidence of ischemic stroke and transient ischemic attack. A confluence of various factors such as blood stasis, endothelial dysfunction, and prothrombotic state could be contributing to the thrombogenesis in AF. Anticoagulation is the first-line therapy for the prevention of thromboembolism by AF. In current days, non-vitamin K dependent oral anticoagulants (NOAC) are considered as the preferred choice of anticoagulants to prevent ischemic stroke in patients with AF. NOACs have comparable good efficacy and better safety with a predictable anticoagulant effect without the routine coagulation monitoring compared to vitamin K dependent oral anticoagulant. However, the proper use of NOACs needs a careful approach to many practical aspects for balancing the preventing thromboembolic events and bleeding risk. Thus, understanding the drug metabolism and indication of NOAC for a specific situation is essential. In this article, we review major clinical trials, the mechanism, and the use of NOACs in the actual clinical setting of managing ischemic stroke patients.

Pulmonary Embolism

Pulmonary embolism (PE) is a life-threatening disease and the third most frequent cardiovascular cause of death after stroke and myocardial infarction. The annual incidence is increasing (in Germany from 85 cases per 100000 population in the year 2005 to 109 cases per 100000 population in the year 2015). The individual risk for PE-related complications and death increases with the number of comorbidities and severity of right ventricular dysfunction. Using clinical, laboratory and imaging parameters, patients with PE can be stratified to four risk classes (high, intermediate-high, intermediate-low and low risk). This risk stratification has concrete therapeutic consequences ranging from out-of-hospital treatment of low-risk patients to reperfusion treatment of (intermediate)-high-risk patients. For haemodynamically unstable patients, treatment decision should preferably be made in interdisciplinary "Pulmonary Embolism Response Teams" (PERT). Due to their comparable efficacy and preferable safety profile compared to vitamin-K antagonists (VKAs), non-vitamin K-dependent oral anticoagulants (NOACs) are increasingly considered the treatment of choice for initial and prolonged anticoagulation of patients with pulmonary embolism. Use of low molecular weight heparins (LMWHs) is recommended for PE patients with cancer; however, recent studies indicate that treatment with factor Xa-inhibitors may be effective and safe (in patients without gastrointestinal cancer). Only prolonged anticoagulation (in reduced dosage) will ensure reduction of VTE recurrence and should thus be considered for all patients with unprovoked events.

Edoxaban dosing patterns in real life practice – Results from the DRESDEN NOAC REGISTRY

Edoxaban is a non-vitamin K dependent oral anticoagulant (NOAC) licensed for venous thromboembolism treatment or stroke prevention in atrial fibrillation. Effectiveness and safety of edoxaban depends on adequate dosing, for which renal function, body weight and drug-drug interactions are important. Edoxaban dosing pattern data outside of clinical trials are scarce. Using data from the prospective DRESDEN NOAC REGISTRY we analysed dosing of 1635 edoxaban patients.Between January 2016 and May 2021, 1652 edoxaban treated patients were enrolled and 1635 patients included in the dosing analysis. At baseline, 1257 patients (76.9%) received edoxaban 60 mg daily, 378 patients (23.1%) 30 mg daily. Patients receiving edoxaban 60 mg were more often male, younger and less often had concomitant diseases such as cancer, renal impairment or organ transplantation. Edoxaban dosing was according to label in 1432 (87.6%) and not according to label in 203 patients (6.5% non-recommended 60 mg and 5.9% non-recommended 30 mg). Renal impairment was the dominating reason for dose adjustment, followed by body weight ≤60 kg. Edoxaban dosing was more often adequate in patients younger than 75 years and in male patients compared to older or female patients.Taken together, edoxaban dosing was adequate in up to 90% of patients, with renal impairment being the most important factor for dose reduction. Use of strong P-gp inhibitors was a rare finding and dose reduction was appropriately performed in the majority of these patients. Inadequate dosing seems more frequent in female or older patients and in transplant recipients, indicating areas for further research.

Anticoagulation after heart valve replacement

In patients after mechanical heart valve replacement anticoagulation is required for the prevention of thrombotic and thromboembolic events. In this setting oral anticoagulation can only be performed with vitaminK antagonists (VKA), while currently all available non-vitaminK dependent oral anticoagulants (NOAC) are contraindicated in patients with mechanical heart valve replacement. This review deals with anticoagulation in patients with mechanical heart valve replacement as well as coagulation inhibition after bioprosthetic or percutaneous valve replacement. In addition, recommendations are given for antithrombotic medication in patients with mechanical heart valve replacement in various clinical scenarios.

Temporal Trends in Pharmacological Stroke Prevention in Patients with Acute Ischemic Stroke and Known Atrial Fibrillation

IntroductionOral anticoagulation (OAC) substantially reduces stroke risk in patients with atrial fibrillation (AF) at risk for stroke. Whether non-vitamin K-dependent oral anticoagulants (NOACs) improve OAC use in stroke prevention requires investigation. MethodsTo investigate temporal trends of OAC use in patients with known AF pre-stroke, we retrospectively analyzed records of 6,803 stroke patients admitted in 2003-2004 (n=1,496), 2008-2010 (n=1,638) or 2013-2015 (n=3,669) to the Charité-Universitätsmedizin Berlin, Germany. Adjusted regression models were used to identify factors associated with OAC use. ResultsOf 1,209 AF patients (mean age 79 years, 55.9% female) with given indication for OAC according to the CHADS2/CHA2DS2-VASc score, 484 (40.0%) were anticoagulated prior to the index stroke, 458 (37.9%) received antiplatelets and 236 (19.5%) had no antithrombotic medication. Compared to 2003-2004 and 2008-2010, there was a higher rate of pre-admission OAC in 2013-2015 (28.2% vs. 49.6%, p<0.001). After adjustment for possible confounders, factors associated with OAC pre-admission were young age (OR 0.74 per decade [95%CI 0.64-0.85]), previous stroke/TIA (OR 1.29 [95%CI 1.00-1.67]), absence of heart failure (OR 0.63 [95%CI 0.47-0.85]) and admission in 2013-2015 (OR 2.45 [95%CI 1.91-3.15]). Prescription of OAC at hospital discharge increased from 2003-2010 compared to 2013-2015 (45.2% vs. 69.5%, p < 0.001). ConclusionsIrrespective of temporal trends and despite given indication, more than half of all patients with known AF were not anticoagulated prior to the index stroke. In the NOAC era, there was an increase in OAC intake pre-stroke and a higher rate of OAC prescription at hospital discharge in stroke survivors with known AF.

Dilemmasituation: Orale Antikoagulation bei Dialysepatienten mit Vorhofflimmern

In patients with intact kidney function and in patients with mild to moderate chronic kidney disease (CKD), strong evidence suggests the use of non-vitamin K dependent oral anticoagulants (NOAC) for preventing ischemic strokes and systemic thromboembolic events in patients with non-valvular atrial fibrillation (nvAF) and elevated thromboembolic risk. In contrast, less evidence is available on the risk-benefit ratio of oral anticoagulation (OAC) in patients with nvAF and severe CKD, particularly in dialysis patients. No large randomised study has tested whether OAC will reduce the risk of thromboembolic events in nvAF without prohibitively high bleeding risk, and whether NOACs or vitamin K antagonists are the superior strategy for OAC. Considering absence of strong evidence, the authors suggest that in dialysis patients with nvAF, in whom the treatment team sees the clear need to prevent thromboembolic events, the use of NOACs or left atrial appendage occlusion should be preferred over treatment with vitamin K antagonists. Any OAC treatment for dialysis patients with nvAF is not in-label in most European countries.

P472Cerebral thromboembolic risk in atrial fibrillation ablation: a direct comparison of vitamin K antagonists versus non-vitamin K-dependent oral anticoagulants

Abstract Aims Cerebral thromboembolic events are well-known complications of pulmonary vein isolation (PVI) and can manifest as stroke or silent cerebral embolic lesions. Over the last years, the preferred oral anticoagulation in atrial fibrillation (AF) shifted from vitamin K antagonists (VKA) to non-vitamin K-dependent oral anticoagulants (NOAC). The aim of this study was to compare the incidence of cerebral embolic lesions after AF ablation in patients on VKA versus patients on NOAC, and to identify corresponding clinical and procedural risk factors. Methods A total of 421 patients undergoing PVI (by radiofrequency catheter or cryoballoon) were prospectively included into the study. Of these, 43.7% were on VKA and 56.3% on NOAC treatment. In the NOAC group 38% of patients had an interruption of anticoagulation for 24-36 hours. All patients underwent pre- and postprocedural cerebral magnetic resonance imaging. Results Periprocedural cerebral lesions occurred in 13.1% overall. Of these, three (0.7%) resulted in symptomatic cerebrovascular accidents. Incidence of cerebral lesions was significantly higher in patients on NOAC compared to VKA (16% vs. 9.2% respectively, p = 0.04), as well as in patients that had intraprocedural cardioversions compared to no cardivoersions (19.5% vs. 10.4% respectively, p = 0.03). In multivariate analysis both parameters were found to be independent risk factors for cerebral embolism. No significant difference between interrupted and uninterrupted NOAC administration could be detected. Conclusions In patients undergoing AF ablation, we identified the use of NOAC and intraprocedural cardioversion as independent risk factors for the occurrence of periprocedural cerebral embolic lesions. Abstract Figure. Incidence of cerebral embolic lesions

Cerebral thromboembolic risk in atrial fibrillation ablation: a direct comparison of vitamin K antagonists versus non-vitamin K-dependent oral anticoagulants.

Cerebral thromboembolic events are well-known complications of pulmonary vein isolation (PVI) and can manifest as stroke or silent cerebral embolic lesions. The aim of this study was to compare the incidence of cerebral embolic lesions (including silent cerebral embolism and stroke) after AF ablation in patients on vitamin K antagonists versus patients on non-vitamin K-dependent oral anticoagulants, and to identify corresponding clinical and procedural risk factors. A total of 421 patients undergoing PVI were prospectively included into the study. Of these, 43.7% were on VKA and 56.3% on NOAC treatment (dabigatran, rivaroxaban, apixaban, and edoxaban). In the NOAC group, 38% of patients had an interruption of anticoagulation for 24-36h. All patients underwent pre- and postprocedural cerebral magnetic resonance imaging. Periprocedural cerebral lesions occurred in 13.1% overall. Of these, three (0.7%) resulted in symptomatic cerebrovascular accidents and 52 (12.4%) in silent cerebral embolic lesions. Incidence of cerebral lesions was significantly higher in patients on NOAC compared with VKA (16% vs. 9.2%, respectively, p = 0.04), and in patients who had intraprocedural cardioversions compared with no cardivoersions (19.5% vs. 10.4%, respectively, p = 0.03). In multivariate analysis, both parameters were found to be independent risk factors for cerebral embolism. No significant difference between interrupted and uninterrupted NOAC administration could be detected. In patients undergoing AF ablation, we identified the use of NOAC and intraprocedural cardioversion as independent risk factors for the occurrence of periprocedural cerebral embolic lesions.

P4741Oral anticoagulants and their effect on kidneys function, is warfarin safe?

Abstract Introduction Patients with atrial fibrillation (AF) and an intermediate or higher risk of stroke and systemic embolization should be treated with oral anticoagulants (OAC). For patients who do not have mitral valve stenosis or a mechanical valve prosthesis, non-vitamin-K dependent oral anticoagulants (NOAC) are preferred over vitamin K antagonists (VKA). All four NOACs are partly eliminated by the kidneys. At the present time it is uncertain which of the two types of anticoagulants – VKA or NOAC – has a lesser deleterious effect on a kidney function. Purpose To estimate the influence of the prolonged treatment with OAC on a kidney function. Methods The retrospective analysis of 776 inpatients with AF admitted from January 1, 2014 to June 30, 2018. Results While in a hospital, 93.6% of AF patients received OAC, of which 50.0% was VKA and 43.6% - NOAC; 1.8% were given antiplatelet therapy (APT) and 4.6% of patients did not receive any antithrombotic therapy (ATT). eGFR was assessed as &gt;90 ml/min in 6.7% of patients, 89 to 60 ml/min – in 45.1% of patients, 59–45 ml/min – in 30.5% of patients, 44 to 30 ml/min – in 13.3% of patients, 29 to 15 ml/min – in 4.1% of patients, and &lt;15 ml/min – in 0.3% of patients. For the analysis of the effect of long-term ATT on the kidney function, 70 patients were selected. Among them, 25 received VKA, 25 received NOAC, 20 patients were on APT (acetylsalicylic acid – ASA). The difference between baseline characteristics of groups was statistically insignificant. After 3.5 years eGFR decreased significantly in VKA group (from 63.69±14.69 ml/min to 48.08±11.2 ml/min, p=0.002); in the NOAC group mean eGFR value was also lower than initial (62.38±16.01 ml/min vs 63,75±21.17 ml/min), but the difference was statistically insignificant (p=0.86). In ASA group eGFR declined from 62,41±17.23 ml/min to 58.25±10.48 ml/min, however, as in the NOAC group, the difference was statistically insignificant (p=0.054). After 3.5 years, significant difference was present between the eGFR values in VKA group and NOAC group (p=0.01), and between the eGFR values in VKA and ASA groups (p=0.02). Decrease of eGFR ≥20% is detected in 31.8% of patients in VKA group, 17.7% of patients in ASA group, and 9.1% of patients in NOAC group. Conclusion In real clinical practice, long-term VKA use leads to more significant reduction in the glomerular filtration rate compared to NOAC use. Although the glomerular filtration rate in the ASA patients decreased to a lesser extent than in those on VKA, ASA should not be used for the stroke and systemic embolism prevention in patients with AF due to its low efficacy.

Anticoagulation and anti platelet therapy in patients with chronic kidney disease

Due to a high rate of cardiovascular events and the high-incidence of atrial fibrillation, many patients with chronic kidney disease (CKD) need to be anticoagulated and/or be subjected to anti platelet therapy (APT). As most studies historically excluded patients with CKD and a creatinine-clearance below 30 ml/min, guidelines for this patient group are only slowly being renewed depending on emerging study data.In patients with CKD stage 1-3, any non-vitamin K dependent oral anticoagulant (NOAC) should be preferentially used over vitamin K antagonists (VKA). In CKD stage 4, dabigatran should be avoided.The decision to anticoagulate a maintenance dialysis patient with atrial fibrillation has to be made on an individual basis considering their thrombosis and bleeding risk. Currently, in Europe all oral anticoagulants can be used only on an off-label basis in these patients. Randomized controlled trials investigating the efficacy and safety of apixaban versus VKA are currently underway. Alternative treatment options (e. g. left appendage occlusion) should be considered.Study data on APT in moderate to advanced CKD are similarly scarce. Despite APT not being renally eliminated, bleeding risk is increased due to uremic platelet dysfunction. When combining APT with NOAC, dose reduction of the latter needs to be addressed.