Prevention Of Thromboembolic Events Research Articles

#2147 Enoxaparin dosing in advanced chronic kidney disease: importance of monitoring with anti-Xa levels

Abstract Background and Aims Enoxaparin is a low-molecular-weight heparin (LMWH) that is commonly used in the prevention of deep venous thrombosis (DVT) and the treatment of acute thomboembolic diseases. Current literature indicates that in advanced chronic kidney disease (CKD), there is a reduced clearance and increased half-life of LMWH and therefore, a dose adjustment is recommended. The prescription label recommends a dose adjustment of enoxaparin to 0.5 mg/kg/day for prophylaxis of DVT and 1 mg/kg/day for therapeutic anticoagulation when eGFR <30 ml/min. The aim of this study was to examine the accuracy of this dosing strategy to achieve the desired target of anticoagulation in advanced CKD. Method We conducted a prospective study in patients admitted from May 2019 to April 2023 in the Nephrology ward at our centre, who started anticoagulant treatment with enoxaparin during their in-hospital stay for prophylactic or therapeutic indications. We excluded patients with eGFR >30 ml/min at the onset of anticoagulation with enoxaparin. The dosing strategy was 0.5 mg/kg/day for prophylaxis of DVT and 1 mg/kg/day for therapeutic anticoagulation in all patients. Blood samples were drawn 4 hours after the third dose of enoxaparin to monitor anti-Xa levels in all cases. Results The study included 153 patients; 70 patients with stage 4-5 CKD and 83 patients on renal replacement therapy. 132 patients (86.3%) received enoxaparin for a therapeutic indication, while 21 patients (13.7%) received it as prophylaxis of DVT. In patients receiving enoxaparin for a therapeutic indication, 73 patients (55.3%) reached the therapeutic target anti-Xa levels (0.6-1), while 32.6% of patients had peak anti-Xa levels below the therapeutic target (<0.6) and 12.1% were over-anticoagulated (>1). There was an inverse relationship between the proportion of patients who were adequately anticoagulated and CKD stage; 66.7%, 58.6% and 48.6% of patients reached the target peak anti-Xa levels in CKD stage 4, 5 and 5D respectively. There was no significant association between anti-Xa levels and obesity or liver disease. In patients receiving enoxaparin for prophylaxis of DVT, 42.9% reached the target anti-Xa levels for prophylaxis (0.3-0.6), while 38.1% had anti-Xa levels below this range and 19% were over-anticoagulated. Conclusion The enoxaparin dosing recommendations indicated by its label entails a high proportion of patients with advanced CKD who do not achieve the target therapeutic levels of antiXa, especially in patients on renal replacement therapy. To ensure adequate anticoagulation in these patients, we recommend using individualized dosing adjustments based on monitoring of anti-Xa levels for the prevention of thromboembolic events and reducing the risk of hemorrhagic events.

Clinical guideline on reversal of direct oral anticoagulants in patients with life threatening bleeding.

Anticoagulation is essential for the treatment and prevention of thromboembolic events. Current guidelines recommend direct oral anticoagulants (DOACs) over vitamin K antagonists in DOAC-eligible patients. The major complication of anticoagulation is serious or life-threatening haemorrhage, which may necessitate prompt haemostatic intervention. Reversal of DOACs may also be required for patients in need of urgent invasive procedures. This guideline from the European Society of Anaesthesiology and Intensive Care (ESAIC) aims to provide evidence-based recommendations and suggestions on how to manage patients on DOACs undergoing urgent or emergency procedures including the treatment of DOAC-induced bleeding. A systematic literature search was performed, examining four drug comparators (dabigatran, rivaroxaban, apixaban, edoxaban) and clinical scenarios ranging from planned to emergency surgery with the outcomes of mortality, haematoma growth and thromboembolic complications. The GRADE (Grading of Recommendations, Assessment, Development and Evaluation) methodology was used to assess the methodological quality of the included studies. Consensus on the wording of the recommendations was achieved by a Delphi process. So far, no results from prospective randomised trials comparing two active comparators (e.g. a direct reversal agent and an unspecific haemostatic agent such as prothrombin complex concentrate: PCC) have been published yet and the majority of publications were uncontrolled and observational studies. Thus, the certainty of evidence was assessed to be either low or very low (GRADE C). Thirty-five recommendations and clinical practice statements were developed. During the Delphi process, strong consensus (>90% agreement) was achieved in 97.1% of recommendations and consensus (75 to 90% agreement) in 2.9%. DOAC-specific coagulation monitoring may help in patients at risk for elevated DOAC levels, whereas global coagulation tests are not recommended to exclude clinically relevant DOAC levels. In urgent clinical situations, haemostatic treatment using either the direct reversal or nonspecific haemostatic agents should be started without waiting for DOAC level monitoring. DOAC levels above 50 ng ml-1 may be considered clinically relevant necessitating haemostatic treatment before urgent or emergency procedures. Before cardiac surgery under activated factor Xa (FXa) inhibitors, the use of andexanet alfa is not recommended because of inhibition of unfractionated heparin, which is needed for extracorporeal circulation. In the situation of DOAC overdose without bleeding, no haemostatic intervention is suggested, instead measures to eliminate the DOACs should be taken. Due to the lack of published results from comparative prospective, randomised studies, the superiority of reversal treatment strategy vs. a nonspecific haemostatic treatment is unclear for most urgent and emergency procedures and bleeding. Due to the paucity of clinical data, no recommendations for the use of recombinant activated factor VII as a nonspecific haemostatic agent can be given. In the clinical scenarios of DOAC intake before urgent procedures and DOAC-induced bleeding, practitioners should evaluate the risk of bleeding of the procedure and the severity of the DOAC-induced bleeding before initiating treatment. Optimal reversal strategy remains to be determined in future trials for most clinical settings.

In adults with NVAF, which intervention best balances the prevention of thromboembolic events: stroke and systemic embolism with safety from bleeding complications?

In adults with NVAF, which intervention best balances the prevention of thromboembolic events: stroke and systemic embolism with safety from bleeding complications?

Practical guide on left atrial appendage closure for the non-implanting physician: an international consensus paper.

A significant proportion of patients who suffer from atrial fibrillation (AF) and are in need of thromboembolic protection are not treated with oral anticoagulation or discontinue this treatment shortly after its initiation. This undertreatment has not improved sufficiently despite the availability of direct oral anticoagulants which are associated with less major bleeding than vitamin K antagonists. Multiple reasons account for this, including bleeding events or ischaemic strokes whilst on anticoagulation, a serious risk of bleeding events, poor treatment compliance despite best educational attempts, or aversion to drug therapy. An alternative interventional therapy, which is not associated with long-term bleeding and is as effective as vitamin K anticoagulation, was introduced over 20 years ago. Because of significant improvements in procedural safety over the years, left atrial appendage closure, predominantly achieved using a catheter-based, device implantation approach, is increasingly favoured for the prevention of thromboembolic events in patients who cannot achieve effective anticoagulation. This management strategy is well known to the interventional cardiologist/electrophysiologist but is not more widely appreciated within cardiology or internal medicine. This article introduces the devices and briefly explains the implantation technique. The indications and device follow-up are more comprehensively described. Almost all physicians who care for adult patients will have many with AF. This practical guide, written within guideline/guidance boundaries, is aimed at those non-implanting physicians who may need to refer patients for consideration of this new therapy, which is becoming increasingly popular.

Is the current therapeutic dosage of nadroparin adequate for neonates and infants under 8 months with thromboembolic disease? a population pharmacokinetic study from a national children's medical center.

Objectives: Nadroparin, a low-molecular-weight-heparin is commonly used off-label in neonates and infants for thromboembolic events prevention. However, the recommended dosing regimen often fails to achieve therapeutic target ranges. This study aimed to develop a population pharmacokinetic (PK) model of nadroparin to determine an appropriate dosing regimen for neonates and infants less than 8 months. Methods: A retrospective chart review was conducted on patients treated with nadroparin at Children's Hospital of Fudan University between July 2021 and December 2023. A population PK model was developed using anti-Xa levels, and its predictive performance was evaluated internally. Monte Carlo simulations were performed to design an initial dosing schedule targeting anti-Xa levels between 0.5 and 1IU/mL. Results: A total of 40 neonates and infants aged less than 8 months with gestational age ranging from 25 to 41 weeks treated with nadroparin were enrolled in the study for analysis. A one-compartment PK model with first order absorption and elimination was adequately fitted to the data. Creatinine clearance was identified as a significant factor contributing to inter-individual variability in clearance. The typical population parameter estimates of clearance, distribution volume and absorption rate in this population were 0.211L/h, 1.55L and 0.495h-1, respectively. Our findings suggest that current therapeutic doses of nadroparin (150-200IU/kg q12h) may result in subtherapeutic exposure, thus higher doses might be required. Conclusion: The present study offers the first estimation of PK parameters for nadroparin in preterm or term neonates and infants less than 8 months utilizing the model. Our findings have potential implications for recommending initial personalized dosages, particularly among patient populations exhibiting similar characteristics.

Efficacy and Safety of Direct Oral Anticoagulants in Pediatric Venous Thromboembolism: A Systematic Review and Meta-Analysis.

To assess the efficacy and safety of direct oral anticoagulants (DOACs) in comparison to standard-of-care (SOC) anticoagulants in the management and prophylaxis of thromboembolic events in pediatric populations. A comprehensive search of electronic databases was conducted to identify relevant studies published between January 1, 2015, and December 18, 2022. A meta-analysis was undertaken to evaluate the effect of DOACs on clinically significant endpoints, employing trial-level data with harmonized endpoint definitions. The primary outcome was venous thromboembolism (VTE). Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. The study was registered with INPLASY (2022120065). Three studies encompassing 934 subjects were included. The incidence of VTE was reduced in patients administered DOACs compared to those on SOC anticoagulants (OR 0.41 [95% CI 0.19-0.93], I²=0%, P = 0.03). No significant differences were observed between the DOAC and SOC groups in all-cause mortality (OR 0.50 [95% CI 0.07-3.59], I²=0%, P = 0.35) or serious adverse events (OR 0.75 [95% CI 0.50-1.12], I²=0%, P = 0.16). The risk of major bleeding (OR 0.50 [95% CI 0.13-1.87], I²=44%, P = 0.30) and clinically relevant non-major bleeding (OR 1.23 [95% CI 0.50-3.00], I²=0%, P = 0.65) exhibited no significant differences between the groups. DOACs are associated with a reduced risk of VTE in pediatric patients without increasing the risk of bleeding, all-cause mortality, or serious adverse events when compared to SOC anticoagulants. DOACs may be an alternative for the treatment and prevention of thromboembolic events in the pediatrics.

One year clinical outcome of dual anti-platelet therapy with the Novel Ticagrelor plus Aspirin versus Clopidogrel plus Aspirin for Endovascular Intervention of patients with Intracranial Aneurysm: A meta-analysis

BackgroundThe use of stents to treat un-ruptured intracranial aneurysms was first approved in the year 2002 in the United States as a Humanitarian Device Exemption. Antiplatelet therapy is mandatory following stent placement. Dual antiplatelet therapy (DAPT) with aspirin and clopidogrel has been the first line agents for the prevention of thromboembolic events following neuro-endovascular procedures. However, clopidogrel hypo-responsiveness has often been observed. In this analysis, we aimed to systematically compare one year clinical outcome of DAPT with the Novel Ticagrelor plus Aspirin versus Clopidogrel plus Aspirin for Endovascular Intervention of patients with Intracranial Aneurysm. MethodsOnline electronic databases were searched from June 2023 till July 2023 for relevant studies which compared DAPT with ticagrelor or clopidogrel for endovascular intervention in patients with intracranial aneurysm. The endpoints which were analyzed were classified into thromboembolic and hemorrhagic events. A fixed and a random effect statistical model were used during data analysis respectively. Risk ratio (RR) with 95 % confidence interval (CI) was used to represent the data following analysis. ResultsFive studies with a total number of 893 participants were included in this analysis. Three hundred and fifty eight (358) participants were assigned to the ticagrelor group whereas 535 participants were assigned to clopidogrel group. Participants’ enrollment period ranged from the year 2009 to 2019. Our results showed that during a mean follow-up time period of one year, DAPT with ticagrelor was associated with significantly lower thromboembolic events with RR: 0.33, 95 % CI: 0.16 – 0.68; P = 0.003. In addition, at one year, DAPT with ticagrelor was not associated with any increase in hemorrhagic events (RR: 0.66, 95 % CI: 0.29 – 1.50; P = 0.32) when compared to DAPT with clopidogrel. ConclusionAt one year, DAPT with ticagrelor was associated with significantly lower thromboembolic events without any increase in hemorrhagic events when compared to clopidogrel associated DAPT for endovascular intervention of patients with intracranial aneurysm. However, even though ticagrelor-associated DAPT use appeared to be more effective and safe, this hypothesis should only be confirmed in larger upcoming trials.

Direct oral anticoagulants versus vitamin k antagonists in patients with atrial fibrillation and bioprosthesis: a systematic review and meta-analysis

Abstract Background/Introduction The large randomized clinical trials published to date have shown that direct oral anticoagulants (DOACs) are as or more effective than vitamin K antagonists (VKAs) in the prevention of thromboembolic events in atrial fibrillation (AF) and generally show a better bleeding risk profile. However, patients with bioprosthetic valves have been underrepresented in RCTs. The aim of this study was to assess the safety and efficacy of DOAC in patients with AF and bioprosthetic valves through a systematic review and meta-analysis including recent evidence from comparative cohort studies and real-world results. Methods A systematic review of the scientific literature and a subsequent meta-analysis were carried out. We included RCTs or comparative observational studies, published from January 2017 to January 2022 comparing DOACs versus vitamin K antagonists in patients with AF or atrial flutter and bioprostheses. We collected data of all-cause mortality, major bleeding, and systemic embolism. The primary outcome of interest was all-cause mortality. Secondary outcomes were systemic embolism or stroke. The primary safety outcome was major bleeding. Results Our analysis included 12 studies, 4 RCTs and 8 observational studies that enrolled a total of 30.283 patients. All-cause mortality 6 observational and 3 RCT were combined. A 9% reduction was found for all-cause mortality in patients treated with DOACs (HR,0.91; P=.0068;95%CI,0.85–0.97;I2=8%). Stroke and systemic embolism 4 RCT and 8 observational studies were combined. No evidence showing a significant effect of DOAC therapy on risk reduction for stroke and embolism was obtained (HR, 0.87; P =.29; 95%CI, 0.67–1.14; I2=45%). Major bleeding The results of the 12 studies were combined. A robustness analysis was performed, and the ENVISAGE RCT was identified as atypical. We therefore proceeded to re-run the meta-analysis without this study’s results. The overall effect size was HR, 0.79 (P = .0001; 95%CI, 0.73-0.85; I2 = 0%), with a 21.1% reduction of major bleeding with DOAC therapy compared with VKA. The present study has several limitations. It has the inherent limitations of the studies included and the combination of findings from comparative observational cohort studies and ad hoc studies from RCTs, which entails a potential source of bias. Second, individual risks for each type of bioprosthesis were not studied. Finally, the four currently marketed DOACs were included in our meta-analysis, but their efficacy and safety were not evaluated separately. Conclusions Our study found that DOAC therapy is associated with a significant reduction of all-cause mortality with no significant increase in the risk of systemic embolism or stroke. This reduction could be attributed to a decrease in major bleeding. Our results therefore suggest that DOACs could be a safer alternative than VKAs in this group of patients.

Abstract 14362: The Columbia Score Predicts Incident Atrial Fibrillation and Flutter in Patients With Transthyretin Cardiac Amyloidosis

Introduction: Atrial fibrillation/flutter (AF) is common in transthyretin cardiac amyloidosis (ATTR-CA). Given the high risk of systemic embolism, there is growing interest in the role of clinical scores for predicting new onset AF in affected patients to potentially guide early prevention of thromboembolic events. The CHARGE-AF scoring system was previously derived from the general population, but has not been validated in ATTR-CA. The Columbia staging system for ATTR-CA is prognostic for survival, but its utility in predicting incident AF is unknown. This study explored the incidence rate and risk scores for AF in ATTR-CA. Methods: This is a retrospective cohort study of 175 patients diagnosed with ATTR-CA who did not have any prior AF upon initial evaluation. We compared the baseline clinical characteristics of individuals with and without incident AF during subsequent follow-up. AF was ascertained based on review of electrocardiograms, continuous monitoring when available, device interrogations if applicable, and charted history. The Columbia score for amyloidosis staging was computed from: Gilmore stage + daily furosemide dose equivalents (0 points: 0 mg/kg, 1 point: between >0 to 0.5 mg/kg, 2 points: >0.5 to 1 mg/kg, 3 points: >1 mg/kg) + NYHA functional class. Time to event analysis was performed via Cox proportional hazard modeling to determine the factors associated with incident AF. Results: New onset AF developed in 41% (n=71) of ATTR-CA patients, with a median follow-up of 2.0 years for the overall population. Compared to those without incident AF, more patients with incident AF were males (93.0% vs 78.8%); self-identified as white race (78.9% vs 61.5%); and reported NYHA II-IV symptoms (91.5% vs 78.8%); but were less frequently of Hispanic ethnicity (2.8% vs 10.6%) or had a genetic variant (25.4% vs 49.0%), all p<0.05. On multivariable analysis, per point increase in Columbia score (HR 1.21, 95% CI 1.03-1.42, p=0.018) was associated with new onset AF, but gender, variant disease, CHARGE-AF, and left atrial volume index were not. Conclusions: About half of ATTR-CM patients developed incident AF during follow-up, which was predicted by the Columbia score, but not the CHARGE-AF score.

Therapy with direct oral anticoagulants for secondary prevention of thromboembolic events in the antiphospholipid syndrome: a systematic review and meta-analysis of randomised trials

ObjectiveAntiphospholipid syndrome (APS) is a systemic autoimmune disorder characterised by venous thrombosis (VT) or arterial thrombosis (AT) and/or pregnancy morbidity and the presence of antiphospholipid antibodies. Direct oral anticoagulants (DOACs)...

DOAC plasma concentration upon hospital admission in a cohort of trauma patients. An observational real-life study.

Due to a better safety profile, direct oral anticoagulants (DOACs) are increasingly prescribed for prevention of thromboembolic events. However, little is known about DOAC plasma concentrations in trauma patients upon hospital admission. Thus, we investigated the frequency and extent of DOAC possible over- and underdosing in trauma patients upon hospital admission. In this single-center retrospective study, DOAC plasma concentrations of adult trauma patients were analyzed with specific calibrated anti-IIa (dabigatran) and anti-Xa (apixaban, edoxaban and rivaroxaban) tests within 4h after hospital admission. A total of 210 trauma patients, admitted between 2019 and 2022, were included in the analyses. Low DOAC levels < 30ng/mL were detected in 13.3% of the patients. In 7.1% of the patients, DOAC plasma levels ranged between 300-399ng/mL and further 7.1% exhibited plasma concentrations > 400ng/mL. The highest incidence of high to very high DOAC plasma concentration was observed for patients on rivaroxaban and dabigatran. A moderate correlation was observed between dabigatran plasma concentration and estimated glomerular filtration rate (rho = - 0.5338, p = 0.0003). For rivaroxaban no clear association between plasma concentration and liver or renal function could be detected. Patients on statins had significantly higher DOAC concentration in comparison with those not taking statins (153 (76-274) vs 108 (51-217) ng/mL, p = 0.046). The current study revealed that patients on dabigatran and rivaroxaban were prone to higher DOAC plasma levels upon hospital admission in comparison with apixaban and edoxaban. DOAC plasma level measurement in trauma patients might be warranted due to unpredictively low or high plasma concentrations. However, the clinical impact of altered plasma levels on both, bleeding and thromboembolic events, remains to be determined by future studies.

Aspirin is a safe and effective thromboembolic prophylaxis after total knee arthroplasty: a systematic review and meta-analysis.

Patients undergoing total knee arthroplasty (TKA) are at high risk for thromboembolic events compared to non-surgical patients. Both anticoagulants and antiplatelet agents are used as antithrombotic prophylaxis in TKA. The aim of this review is to understand the role of aspirin in the prevention of thromboembolic events and to compare its efficacy and safety with the main anticoagulants used in antithromboembolic prophylaxis in TKA. A systematic review and meta-analysis was performed according to the PRISMA guidelines. An electronic systematic search was conducted using PubMed, Scopus, and the Cochrane Central Registry to evaluate studies that compared aspirin with other anticoagulants, in terms of deep venous thrombosis and pulmonary embolism after TKA. The meta-analysis compared the rate of complications between aspirin and other anticoagulants. Thirteen studies were included in the systematic review for a total of 163,983 patients, and 10 studies were included in the meta-analysis. The meta-analysis demonstrated no statistically significant differences between aspirin and other anticoagulants in terms of the rate of deep venous thrombosis (OR 0.93, 95% CI 0.81-1.08, p = 0.35) and pulmonary embolism (OR 0.89, 95% CI 0.56-1.41, p = 0.61). Aspirin is safe, effective, and not inferior to other main anticoagulants in preventing thromboembolic events following TKA.

Direct oral anticoagulants versus percutaneous left atrial appendage occlusion in atrial fibrillation: 5-year outcomes

BackgroundLAAO is an emerging option for thromboembolic event prevention in patients with NVAF. We previously reported data on comparison between LAAO and DOAC at two-year follow-up in NVAF patients at HBR (HAS-BLED ≥3). AimsLimited data are available on long term follow-up. We aimed to evaluate the efficacy and safety of DOACs versus LAAO indication after 5 years. MethodsWe enrolled 193 HBR treated with LAAO and 189 HBR patients with DOACs. At baseline, LAAO group had higher HAS-BLED (4.2 vs 3.3, p < 0.001) and lower CHADS-VASc (4.3 vs. 4.7, p = 0.005). After 1:1 PSM, 192 patients were included (LAAO n = 96; DOACs n = 96). ResultsAt 5-year follow-up the rate of the combined safety and effectiveness endpoint (ISTH major bleeding and thromboembolic events) was significantly higher in LAAO group (p = 0.042), driven by a higher number of thromboembolic events (p = 0.047). The rate of ISTH-major bleeding events was similar (p = 0.221). After PSM no significant difference in the primary effectiveness (LAAO 13.3% vs DOACs 9.5%, p = 0.357) and safety endpoint (LAAO 7.5% vs DOACs 7.5%; p = 0.918) were evident. Overall bleeding rate was significantly higher in DOACs group (25.0% vs 13.7%, p = 0.048), while a non-significant higher number of TIA was reported in LAAO group (5.4% vs 1.1%, p = 0.098). All-cause and cardiovascular mortality were higher in LAAO group at both unmatched and matched analysis. ConclusionWe confirmed safety and effectiveness of both DOAC and LAAO in NVAF patients at HBR, with no significant differences in thromboembolic events or major bleeding were at 5-year follow-up. The observed increased mortality after LAAO warrants further investigations in RCTs.

Total femoral replacement: a challenging but promising limb salvage option

Total femur replacement is a limb salvage surgery indicated for patients with oncological and non-oncological pathologies of the femur. Given the characteristics of the patients, there are essential perioperative considerations such as the previous treatment with chemotherapy or radiotherapy, prevention of thromboembolic events, hemorrhage management, and booking of an intensive care unit. As demanding as the surgical technique is, preventing extensive fibrosis, major bleeding, acetabular defects, and changes in normal anatomy is possible. The complications described include infection, structural failure, tumor progression, aseptic loosening, and soft tissue failure. Functional results and survival vary from series to series, but reports exist as high as 70% at ten years.

Review of the Etiology, Diagnosis, and Management of Left Ventricular Thrombus.

The incidence of left ventricular (LV) thrombus following acute myocardial infarction has declined significantly due to recent advancements in reperfusion and antithrombotic therapies. The development of LV thrombus depends on Virchow's triad: endothelial injury following myocardial infarction, blood stasis from LV dysfunction, and hypercoagulability. Diagnostic modalities for LV thrombus include transthoracic echocardiography and late gadolinium enhancement cardiac magnetic resonance imaging. Anticoagulation with direct oral anticoagulants or vitamin K antagonists for 3 months following initial diagnosis of LV thrombus remains the treatment of choice for LV thrombus. However, further evidence is needed to demonstrate the noninferiority of direct oral anticoagulants compared with vitamin K antagonists for the prevention of thromboembolic events.

Fibrilación auricular no valvular en pacientes en diálisis peritoneal: prevalencia, tratamiento y profesionales implicados

Atrial fibrillation is the most frequent chronic arrhythmia in patients with chronic kidney disease. Oral anticoagulation with vitamin K antagonists and now direct oral anticoagulants have been and are the fundamental pillar for the prevention of thromboembolic events. However, there are no randomized clinical trials on the risk-benefit profile of oral anticoagulation in patients with chronic kidney disease stage 5 on peritoneal dialysis and there is little evidence in the literature in this population.The objective of our study was to know the prevalence, treatment and professionals involved in the management of atrial fibrillation in peritoneal dialysis patients. For this purpose, we performed a descriptive analysis through a survey sent to different peritoneal dialysis units in Spain. A total of 1403 patients on peritoneal dialysis were included in the study, of whom 186 (13.2%) had non-valvular atrial fibrillation. In addition, the assessment of the scores of thromboembolic and bleeding risks for the indication of oral anticoagulation was mainly carried out by the cardiologist (60% of the units), as well as its prescription (cardiologist 47% in consensus with the nephrologist 43%).In summary, patients on peritoneal dialysis have a remarkable prevalence of non-valvular atrial fibrillation. Patients frequently receive oral anticoagulation with vitamin K antagonists, as well as direct oral anticoagulants. The data obtained regarding the scales used for the assessment of thromboembolic and bleeding risk, treatment and involvement by Nephrology indicates that there is a need for training and involvement of the nephrologist in this pathology.

P465 NON–VITAMIN K ANTAGONIST ORAL ANTICOAGULANTS IN PATIENTS WITH THALASSEMIA

Abstract Apixaban, dabigatran, edoxaban and rivaroxaban (NOACs) are drugs widely used and recommended for the prevention of thromboembolic events in patients with atrial fibrillation (AF) or atrial flutter and to prevent or treat pulmonary embolism (PE) and deep vein thrombosis (DVT). However, very little is reported in literature regarding their use in patients with β–thalassemia, among which high incidence of AF is reported and where the balance between thromboembolic and bleeding risk is of paramount importance. In this study 18 patients with transfusion–dependent β–thalassemia were enrolled. Patients were treated with NOACs for throboembolic prevention due to history of AF or atrial flutter. Mean follow–up duration was 21 ± 15 months for each patient and no thromboembolic events were reported. Three patients had non–major bleeding events without oral anticoagulation interruption. Two patients reported dyspepsia during treatment with dabigatran and were shifted to a different NOAC with resolution of symptom. These data suggest efficacy and safety of NOACs for the prevention of thromboembolic events in patients affected by β–thalassemia.

Low dose rivaroxaban for the management of atherosclerotic cardiovascular disease.

Atherosclerotic cardiovascular disease is characterized by some risk of major adverse events despite the availability of effective medical therapies for secondary prevention. There is emerging evidence suggesting that thrombin partly contributes to this residual risk. In fact, thrombin (i.e., activated coagulation factor II) triggers not only the conversion of fibrinogen to fibrin but also platelet activation and various pathways responsible for pro-atherogenic and/or pro-inflammatory effects through interaction with protease activated receptors. To reduce the risk associated with thrombin activation, oral anticoagulants antagonists of vitamin K showed promise, but were associated with unacceptable bleeding rates. Direct oral anticoagulants targeting the activated factors X and II carry a lower risk of bleeding than vitamin K antagonists. Rivaroxaban, a direct inhibitor of activated factor X approved at the dose of 20mg once daily for the prevention of thromboembolic events, has been also investigated at a reduced dose of 2.5mg twice daily in several alternative scenarios of atherosclerotic cardiovascular disease, in combination with standard of care. Current guidelines recommend that low-dose rivaroxaban is given in an adjunct to standard therapy to patients with stable atherosclerosis and acute coronary syndromes at low bleeding risk. Several studies are underway to evaluate its putative benefits in other clinical settings.

Abstract Number ‐ 140: Transcranial Doppler Emboli Monitoring for Stroke Prevention after Flow Diversion: A Single Center Experience

Introduction Following the favorable clinical and radiographical results of flow diversion, its use has continually expanded for the treatment of complex intracranial aneurysms. The high metal surface of flow diverters (FD) increases the risk of thromboembolic complications. Current emboli monitoring data after FD placement is limited. Transcranial doppler (TCD) offers a non‐invasive evaluation of microembolic signals and might be a valuable tool to prevent ischemic complications. We evaluated the rate of embolic signals and their management after FD implantation. Methods We performed a retrospective, single‐center evaluation of adult patients who underwent a FD procedure with the Pipeline Embolization Device (PED) for unruptured intracranial aneurysms between 2012 and 2016. Covariates included patient demographics, comorbidities, aneurysm characteristics, procedure characteristics, and post‐procedure TCD emboli monitoring (immediate and &gt;12 hours post‐operative). TCD emboli signals were classified as positive (&lt; 15 microembolic signals) and strongly positive (&gt;15 signals). The primary outcome was the rate of symptomatic stroke at 2 and 12 weeks in these patients. Results 105 patients with 132 aneurysms were analyzed. Mean age was 59.7 years, and 78% were females. Mean aneurysm size was 7.8 ± 6.4 mm. Most of them were located in the paraclinoid region (40%). Two PEDs were implanted in 12 (11%) cases and adjunctive coiling was performed in 15 (14%) cases. Microemboli were detected in 11.4% of cases (12/105 patients) after PED deployment. In 5/12 patients, the emboli resolved upon repeat testing with no intervention. In 6/12 patients, further heparinization, additional clopidogrel administration, or change in antiplatelet agents were needed. These treatments reduced the microembolic events. In 1 patient who was clopidogrel‐resistant and a ticagrelor super‐responder, mechanical thrombectomy was necessary due to acute in‐stent thrombosis. There were no symptomatic strokes at 2 and 12 weeks. Conclusions TCD emboli monitoring can be a powerful non‐invasive tool for the early identification and prevention of thromboembolic events after FD implantation. Early detection of microembolic signals offers the possibility to modify postoperative management, avoid silent emboli, and potentially avoid symptomatic strokes.

Optimizing Anticoagulation Management in Atrial Fibrillation: Beyond the Guidelines. How and for Whom?

Anticoagulation therapy (AT) is the cornerstone of atrial fibrillation (AF) treatment for thromboembolic event prevention. The AF burden, however, is of predictive relevance and may be used as a foundation for therapeutic decisions in individuals with paroxysmal or persistent AF. Remote rhythm monitoring devices can provide early detection of the arrhythmia, long-term rhythm monitoring, and the development of anticoagulation strategies based on AF recurrence profile and the total burden of the arrhythmia. Although the exact thromboembolic cut-off value for the AF burden has not yet been established, targeted anticoagulation treatments in the new oral anticoagulants era have shown encouraging outcomes. The combined evaluation of AF burden and patient thromboembolic risk reported in some studies supports the concept of tailored anticoagulation management, at least in a subset of patients with low AF burden and intermediate thromboembolic risk, for whom the guidelines recommend that AT should be individualized based on net clinical benefit and patient values and preferences. Although it is still premature to derive firm conclusions or algorithms diverging from the current guidelines, the combination of a patient's AF burden, thromboembolic risk, and bleeding risk can lead in the future to an individualized management of patients with a congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke, vascular disease, age 65-74 years sex category (female) (CHA 2 DS 2 -VASc) score of 1 (2 for female patients), in whom the guidelines do not strictly recommend long-term AT. In this study, we provide an algorithm regarding the individualized implementation of anticoagulation strategies in AF in different patients' thromboembolic risk profiles, based on the available data on the so far tailored anticoagulation strategies in AF.