Management Of Non-valvular Atrial Fibrillation Research Articles

Anticoagulation status and left atrial appendage occlusion indications in hospitalized cardiology patients with atrial fibrillation: a Hellenic Cardiorenal Morbidity Snapshot (HECMOS) sub-study

Abstract Background Proper use of oral anticoagulants is crucial in the management of non-valvular atrial fibrillation (NVAF) patients. Left atrial appendage occlusion (LAAC) may be considered for stroke prevention in patients with NVAF and contraindications for long-term anticoagulant treatment. Purpose We aimed to assess the anticoagulation status and LAAC indications in patients with NVAF from HECMOS (Hellenic Cardiorenal Morbidity Snapshot) survey. Methods HECMOS was a nationwide snapshot survey of cardiorenal morbidity in hospitalized cardiology patients. HECMOS used an electronic platform to collect demographic and clinically relevant information from all patients hospitalized on March 3, 2022, in 55 different cardiology departments. In this substudy, we included patients with known AF without mechanical prosthetic valves and moderate to severe mitral valve stenosis. Patients with poor adherence to anticoagulants, high bleeding risk, previous major bleeding, and previous stroke were considered candidates for LAAC. Results Two hundred fifty-six patients (mean age 76.6±11.7, 148 males) were included in our analysis. Most of them (n=159; 62%) suffered from persistent AF. Mean CHA 2 DS 2 - VASc score was 4.28±1.7, while mean HAS-BLED score was 1.47±0.9. Three out of 3 patients with a CHA 2 DS 2 -VASc 0 or 1 (female) received improperly anticoagulants. Sixteen out of 18 patients with a CHA 2 DS 2 -VASc 1 or 2 (female) received anticoagulants. Thirty-three out of 235 patients with a CHA 2 DS 2 -VASc > 1 or 2 (for female) did not receive improperly anticoagulants. Among 221 under anticoagulant therapy, 191 (86.4%) received non-vitamin K antagonist oral anticoagulants (NOACs) and 30 (13.6%) received vitamin K antagonists. Relative indications for LAAC were present in 77 patients with NVAF (53 had only one risk factor, while 22 had two and 2 patients had three concurrent risk factors). In detail, 15 reported poor or no adherence to the anticoagulant therapy, 17 patients had a history of major bleeding, 36 had a prior stroke and 35 had a HAS-BLED score ≥3. No LAAC treatment was recorded. Conclusion Αnticoagulation status was nearly optimal in a high thromboembolic risk population of cardiology patients, mainly treated with NOACs. Three out of ten AF patients should be screened for LAAC.Anticoagulation by thrombotic riskPotential LAAC candidates

Safety and efficacy of apixaban versus warfarin in peritoneal dialysis patients with non-valvular atrial fibrillation: protocol for a prospective, randomised, open-label, blinded endpoint trial (APIDP2)

IntroductionSeveral randomised controlled trials have demonstrated that novel oral anticoagulants are safer compared with vitamin K antagonists for the management of non-valvular atrial fibrillation (NVAF) to prevent thromboembolic events in...

Effectiveness and Safety of Edoxaban Compared With Apixaban in Elderly Patients With Nonvalvular Atrial Fibrillation: A Real-World Population-Based Cohort Study.

The very elderly (≥80 years) are at high risk of nonvalvular atrial fibrillation and thromboembolism. Given its recent approval, the comparative effectiveness and safety of edoxaban in this population, relative to the commonly used apixaban, remain unknown. Using the United Kingdom Clinical Practice Research Datalink, we identified a cohort of patients aged ≥80 with incident nonvalvular atrial fibrillation and newly treated with edoxaban or apixaban between 2015 and 2021. Cohort entry was defined as the first prescription for one of the 2 drugs. We used propensity score fine stratification and weighting for confounding adjustment. A weighted Cox proportional hazards model was used to estimate the hazard ratios (HR) with 95% CI of ischemic stroke/transient ischemic attack/systemic embolism (primary effectiveness outcome) and of major bleeding (primary safety outcome) associated with edoxaban compared with apixaban. We also assessed the risk of all-cause mortality and a composite outcome of ischemic stroke/transient ischemic attack, systemic embolism, gastrointestinal bleeding, and intracranial hemorrhage as secondary outcomes. The cohort included 7251 new-users of edoxaban and 39 991 of apixaban. Edoxaban and apixaban had similar incidence rates of thromboembolism (adjusted rates, 20.38 versus 19.22 per 1000 person-years; adjusted HR, 1.06 [95% CI, 0.89-1.26]), although the rates of major bleeding were higher with edoxaban (adjusted rates, 45.57 versus 31.21 per 1000 person-years; adjusted HR, 1.42 [95% CI, 1.26-1.61]). The risk of the composite outcome was 21% higher with edoxaban (adjusted HR, 1.21 [95% CI, 1.07-1.38]). All-cause mortality was similar between edoxaban and apixaban (adjusted HR, 1.04 [95% CI, 0.96-1.12]). In very elderly patients with nonvalvular atrial fibrillation, edoxaban resulted in similar thromboembolism prevention as apixaban, although it was associated with a higher risk of major bleeding. These findings may improve the management of nonvalvular atrial fibrillation by informing physicians on the choice of anticoagulant for this vulnerable population.

Factor Xa Inhibitors versus warfarin in patients with morbid obesity and atrial fibrillation.

Factor Xa Inhibitors have emerged as a first-line agent in the management of non-valvular atrial fibrillation (NVAF), but there is a need for additional data surrounding their use in the morbidly obese population. The purpose of this study was to evaluate whether Factor Xa Inhibitors are as safe and effective as warfarin for the treatment of NVAF in individuals with a BMI ≥ 40 kg/m2 and/or weight ≥ 120 kg. This was a multi-center retrospective cohort study comparing the use of Factor Xa Inhibitors (apixaban and rivaroxaban) to warfarin for the management of NVAF in adult patients with a BMI ≥ 40 kg/m2 and/or weight ≥ 120 kg. The primary outcomes were stroke or systemic embolism and major bleeding within 12months. A total of 3,156 patients were included in the final analysis; 1,396 in the warfarin group and 1760 in the Factor Xa Inhibitor group. The mean weight and BMI of the overall cohort was 134.1kg and 44.7kg/m2, respectively. There was no difference in stroke or systemic embolism (OR 1.21, 95% CI 0.78-1.85) or major bleeding (OR 0.99, 95% CI 0.65 - 1.53) with Factor Xa Inhibitors compared to warfarin after controlling for covariates. This analysis of real-world data suggests no difference in bleeding or thrombotic outcomes for severely obese patients with NVAF taking Factor Xa Inhibitors compared to warfarin. Overall, our study adds further data to support the use of Factor Xa Inhibitors as an alternative to warfarin in severely obese patients with NVAF.

Anticoagulation Status and Left Atrial Appendage Occlusion Indications in Hospitalized Cardiology Patients with Atrial Fibrillation: A Hellenic Cardiorenal Morbidity Snapshot (HECMOS) Sub-Study.

Background and Objectives: The proper use of oral anticoagulants is crucial in the management of non-valvular atrial fibrillation (AF) patients. Left atrial appendage closure (LAAC) may be considered for stroke prevention in patients with AF and contraindications for long-term anticoagulant treatment. We aimed to assess anticoagulation status and LAAC indications in patients with AF from the HECMOS (Hellenic Cardiorenal Morbidity Snapshot) survey. Materials and Methods: The HECMOS was a nationwide snapshot survey of cardiorenal morbidity in hospitalized cardiology patients. HECMOS used an electronic platform to collect demographic and clinically relevant information from all patients hospitalized on 3 March 2022 in 55 different cardiology departments. In this substudy, we included patients with known AF without mechanical prosthetic valves or moderate-to-severe mitral valve stenosis. Patients with prior stroke, previous major bleeding, poor adherence to anticoagulants, and end-stage renal disease were considered candidates for LAAC. Results: Two hundred fifty-six patients (mean age 76.6 ± 11.7, 148 males) were included in our analysis. Most of them (n = 159; 62%) suffered from persistent AF. The mean CHA2DS2-VASc score was 4.28 ± 1.7, while the mean HAS-BLED score was 1.47 ± 0.9. Three out of three patients with a a CHA2DS2-VASc score of 0 or 1 (female) were inappropriately anticoagulated. Sixteen out of eighteen patients with a CHA2DS2-VASc score 1 or 2 (if female) received anticoagulants. Thirty-one out of two hundred thirty-five patients with a CHA2DS2-VASc score > 1 or 2 (if female) were inappropriately not anticoagulated. Relative indications for LAAC were present in 68 patients with NVAF (63 had only one risk factor and 5 had two concurrent risk factors). In detail, 36 had a prior stroke, 17 patients had a history of major bleeding, 15 patients reported poor or no adherence to the anticoagulant therapy and 5 had an eGFR value < 15 mL/min/1.73 m2 for a total of 73 risk factors. Moreover, 33 had a HAS-BLED score ≥ 3. No LAAC treatment was recorded. Conclusions: Anticoagulation status was nearly optimal in a high-thromboembolic-risk population of cardiology patients who were mainly treated using NOACs. One out of four AF patients should be screened for LAAC.

Cost-Effectiveness of Direct Oral Anticoagulants in Patients With Nonvalvular Atrial Fibrillation in Hong Kong

ObjectivesThe emergence of direct oral anticoagulants (DOACs) has revolutionized the prevention of stroke related to nonvalvular atrial fibrillation (NVAF). Several DOACs are available on the market, while the cost-effectiveness comparison among DOACs and vitamin K antagonist (warfarin) in NVAF management in Hong Kong market remains scarce. The objective of this study was to assess the cost-effectiveness of DOACs and warfarin from a Hong Kong public institutional perspective to inform formulary listing decisions. MethodsA previously developed Markov model was adapted to simulate the lifetime disease progression of a hypothetical cohort of 1000 patients. Net monetary costs, quality-adjusted life-year (QALY), and incremental cost-effectiveness ratio were computed for the following competing alternatives: warfarin, apixaban (5 mg twice daily), dabigatran (110 mg or 150 mg twice daily), and rivaroxaban (20 mg once daily). Probabilistic sensitivity analyses were conducted to address study uncertainties. ResultsIn base-case results, all DOACs were associated with greater QALYs improvements and lower costs than warfarin. Rivaroxaban, apixaban, dabigatran 150 mg, dabigatran 110 mg, and warfarin resulted in net costs US dollar (USD) 8088, USD 8240, USD 8566, USD 8653, and USD 16 363 and net QALY 5.87, 6.017, 6.022, 5.98, and 5.829, respectively. In probabilistic sensitivity analysis, the probabilities of warfarin, rivaroxaban 20 mg, dabigatran 110 mg, dabigatran 150 mg, and apixaban 5 mg being cost-effective of 2000 iterations were 0%, 0%, 29.4%, 33.2%, and 37.4%, respectively. ConclusionApixaban was the most cost-effective option compared with other DOACs and warfarin in the management of NVAF; this conclusion is consistent under all the tested uncertainty scenarios.

PD07 Cost-Effectiveness Of Direct Oral Anticoagulants In Chinese Patients With Non-Valvular Atrial Fibrillation

IntroductionThe emergence of direct oral anticoagulants (DOACs) has revolutionized the prevention of stroke-related non-valvular atrial fibrillation (NVAF). Although several DOACs are available, studies comparing the cost effectiveness of DOACs with vitamin K antagonists for NVAF are scarce. The objective of this study was to assess the cost effectiveness of DOACs and warfarin from the Hong Kong public institutional perspective to inform formulary listing decisions.MethodsA previously developed Markov model was adapted to simulate the lifetime disease progression of a hypothetical cohort of 1,000 patients. Net monetary costs, quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratios (ICERs) were computed for the following competing alternatives: warfarin, apixaban (5 mg twice daily), dabigatran 110mg or 150mg (twice daily), and rivaroxaban (20mg once daily). Model inputs were sourced from local real-world evidence, landmark trials, and comprehensive literature reviews. Probabilistic sensitivity analyses and deterministic sensitivity analyses were conducted to address study uncertainties. The willingness-to-pay threshold was set at one times the gross domestic product (GDP) per capita (USD 46,091) per QALY gained.ResultsIn base case results, all DOACs provided greater improvements in QALYs at a lower cost than warfarin. Using apixaban as the reference for comparisons among the DOACs, dabigatran 110 mg resulted in greater costs and lower QALY gains and was dominated by apixaban, whereas dabigatran 150 mg provided an incremental QALY of 0.005 at an incremental cost of USD 326, leading to an ICER of USD 67,633 per QALY. The lifetime cost associated with rivaroxaban was lower than for apixaban (-USD 151), but with lower QALY gains (-0.147), resulting in an ICER of USD 1,029 per QALY. In probabilistic sensitivity analysis, the probability of warfarin, rivaroxaban 20 mg, dabigatran 110 mg, dabigatran 150 mg, and apixaban 5 mg being cost effective out of 2,000 iterations was 0 percent, 0 percent, 29.4 percent, 33.2 percent, and 37.4 percent, respectively.ConclusionsThe results indicated that apixaban was the most cost-effective treatment in the management of NVAF, compared with other DOACs and warfarin. This conclusion was consistent under all the uncertainty test scenarios.

Non-Valvular Atrial Fibrillation: A Systematic Review

Non-Valvular atrial fibrillation is defined as the one which develops in the absence of moderate to severe rheumatic mitral stenosis ,a mechanical or bioprosthetic valve or mitral valve repair. Atrial fibrillation is the most common pathological cardiac arrhythmia and major cause of ischemic stroke. There are many major risk factors for development of atrial fibrillation. Among these advanced age, hypertension, ischemic heart disease, chronic lung disease and consumption of alcohol are the major causes. Aim of treatment is to control the rate, rhythm and anticoagulation so as to prevent tachycardia induced cardiomyopathy, heart failure and stroke. This review article gives a comprehensive and systematic approach for the management of Non-valvular atrial fibrillation.&#x0D; Keywords: Atrial fibrillation (AF), Stroke, Anticoagulation.

Trends of anticoagulant use and outcomes of patients with non-valvular atrial fibrillation: Findings from the RAFFINE registry

BackgroundThe management of non-valvular atrial fibrillation (AF) has evolved with the development of direct oral anticoagulants (DOACs). However, data regarding the effectiveness and safety of DOACs outside clinical trial settings are limited, and off-label dosing of DOACs has not been thoroughly investigated. MethodsWe examined the clinical outcomes of patients with non-valvular AF in the RAFFINE registry, a prospective registry of Japanese patients with AF who were followed-up for more than 3 years. ResultsAmong 3706 patients with non-valvular AF, 42.5% received warfarin and 44.7% received DOACs at baseline. The administration of DOACs increased annually. The mean CHADS2 and HAS-BLED scores were significantly higher in the warfarin group. The unadjusted all-cause mortality, cardiovascular mortality, and incidence of major bleeding events were higher in the warfarin group. The incidence of ischemic stroke/systemic embolism was not different between groups. After adjustment for baseline characteristics, the incidence of these events was not different between groups. Off-label dosing was performed for 32% of patients in the DOAC group, but this did not affect clinical outcomes. ConclusionsThe all-cause mortality, cardiovascular mortality, and incidence of major bleeding events were higher in the warfarin group than in the DOAC group. After adjustment, warfarin use was not associated with an increase in these events. Off-label dosing of DOACs is not rare and is not associated with reduced effectiveness. The impact of off-label dosing of each DOAC on clinical events should be assessed using a larger population.

Appropriate Dosing Regimens of Non-Vitamin K Antagonist Oral Anticoagulants for Treatment of Patients With Non-Valvular Atrial Fibrillation: An Evidence-Based Consideration.

Patients with non-valvular atrial fibrillation (NVAF) exhibit a high risk of stroke, which is associated with high mortality. Thus, stroke prevention is crucial for the overall management of NVAF. Two categories of drugs, vitamin K antagonist warfarin and non-vitamin K antagonist oral anticoagulants (NOACs), are clinically used to prevent NVAF-related stroke. In some circumstances, NOACs are superior to warfarin. However, NOACs selection for NVAF patients is affected by many factors, including individual patient characteristics, comorbidities, risk factors, or laboratory variables. This article summarizes the discrepancy in NOACs management with emphasis on the dosing regimens and influencing factors, such as stroke risk, age, body weight, renal function, gastrointestinal bleeding (GIB) risk, and combination of antiplatelet therapy, in order to identify individual groups with particular clinical characteristics who may obtain more benefit from a certain dosing regimen of NOACs. Determination of a particular subset of patient populations for the appropriate dose regimen of NOACs will help to achieve desired clinical outcomes. Furthermore, to compensate clinical evidence, we should place more emphasis on the findings of current clinical trials and supplement real-world data.

The atrial FibriLlatiOn real World management registry in the Middle East and Africa: design and rationale.

Atrial fibrillation is the most common cardiac arrhythmia, affecting 33.5 million patients globally. It is associated with increased morbidity, leading to significant clinical and economic burden. There exist only limited data in the Middle Eastern region from the existing registries. The goal of the FLOW-AF (atrial FibriLlatiOn real World management registry in the Middle East and Africa) registry is to evaluate the characteristics, treatment patterns, and clinical and economic outcomes associated with anticoagulation among patients newly diagnosed with nonvalvular atrial fibrillation in Egypt, Lebanon, the Kingdom of Saudi Arabia, and the United Arab Emirates. This study will be a multicountry, multicenter, prospective observational registry aiming to enroll 1446 newly diagnosed nonvalvular atrial fibrillation patients at more than 20 sites across the four countries. During the recruitment period, patients will be included if they were newly diagnosed with nonvalvular atrial fibrillation and had initiated treatment for the prevention of stroke/systemic embolism. Patient data will be assessed prospectively at 6 and 12 months from their enrollment date. Demographics, clinical characteristics, antithrombotic treatments received, clinical outcomes, adverse events, healthcare resource utilization, and direct costs associated with management of nonvalvular atrial fibrillation will be collected and analyzed overall, by country, and by groups created based on treatment, demographics, and clinical characteristics, medical history and risk factors. The FLOW-AF registry will provide information on the uptake of oral anticoagulants, treatment patterns, clinical outcomes, and healthcare utilization and costs among newly diagnosed nonvalvular atrial fibrillation patients in the Middle Eastern region.

RIVAROXABAN VERSUS WARFARIN IN AFRICAN AMERICAN PATIENTS WITH NONVALVULAR ATRIAL FIBRILLATION

African American patients were under-represented in randomized trials evaluating non-vitamin K oral anticoagulants for the management of non-valvular atrial fibrillation (NVAF). We evaluated the effectiveness and safety of rivaroxaban vs. warfarin in African American patients with NVAF managed in

Prescribers' perceptions of benefits and limitations of direct acting oral anticoagulants in non-valvular atrial fibrillation.

Background:There is an acknowledged lack of robust and rigorous research focusing on the perspectives of those prescribing direct acting oral anticoagulants (DOACs) for non-valvular atrial fibrillation (AF).Objective:The objective was to describe prescribers’ experiences of using DOACs in the management of non-valvular AF, including perceptions of benefits and limitations.Methods:A cross-sectional survey of prescribers in a remote and rural area of Scotland. Among other items, the questionnaire invited free-text description of positive and negative experiences of DOACs, and benefits and limitations. Responses were independently analysed by two researchers using a summative content analysis approach. This involved counting and comparison, via keywords and content, followed by interpretation and coding of the underlying context into themes.Results:One hundred and fifty-four responses were received, 120 (77.9%) from physicians, 18 (11.7%) from nurse prescribers and 10 (6.4%) from pharmacist prescribers (6 unidentified professions). Not having to monitor INR was the most cited benefit, particularly for prescribers and patients in remote and rural settings, followed by potentially improved patient adherence. These benefits were reflected in respondents’ descriptions of positive experiences and patient feedback. The main limitations were the lack of reversal agents, cost and inability to monitor anticoagulation status. Many described their experiences of adverse effects of DOACs including fatal and non-fatal bleeding, and upper gastrointestinal disturbances.Conclusions:While prescribers have positive experiences and perceive benefits of DOACs, issues such as adverse effects and inability to monitor anticoagulation status merit further monitoring and investigation. These issues are particularly relevant given the trajectory of increased prescribing of DOACs.

A Review of the Medical Challenges of Using Direct Oral Anticoagulants in Real-World Practice.

Clinical guidelines for management of non-valvular atrial fibrillation or venous thromboembolism currently recommend direct oral anticoagulants as the preferred strategy for antithrombotic treatment. As a result, they are increasingly being used as an alternative to conventional therapy. However, they are unlikely to completely replace conventional approaches, due to a number of existing medical challenges. These challenges relate to the uncertainty of optimal dose regimens and the strategy of using them in specific patient populations with non-valvular atrial fibrillation or venous thromboembolism. The efficacy and safety profile of dabigatran among various regions may differ, depending on regional variations in dosing recommendations. Furthermore, optimal dose regimens may be different between Asian and non-Asian populations. It will be necessary to collect real-world clinical data on the use of edoxaban in patients with non-valvular atrial fibrillation with high-creatinine clearances, to determine the optimal dose required for stroke protection. In addition, the efficacy of combination therapy utilizing direct oral anticoagulants and antiplatelet agents has not yet been established in patients with non-valvular atrial fibrillation with acute coronary syndrome and/or percutaneous coronary intervention with stenting. Low-molecular-weight heparin is, therefore, suggested to be used in preference to vitamin K antagonists or direct oral anticoagulants in current clinical practice guidelines, as indirect comparisons suggests that oral anticoagulants are less effective than low-molecular-weight heparin. Consequently, we need to focus on the outcomes of ongoing studies and review more real-world data in heterogeneous populations to complement clinical data obtained from controlled studies with highly selective populations. Therefore, direct oral anticoagulants should be used with caution based on individual assessments of thromboembolic and bleeding risks as well as other clinical characteristics.

Rivaroxaban Reduces the Levels of Extracellular Vesicles in Patients with Venous Thromboembolism and Non-Valvular Atrial Fibrillation

Background: Rivaroxaban is a direct oral anticoagulant (DOAC) with similar efficacy to vitamin K antagonists in the management of non-valvular atrial fibrillation (NVAF) and venous thromboembolism (VTE) but with a more favourable bleeding profile. Recent studies including the landmark COMPASS trial have demonstrated that rivaroxaban possesses cardioprotective and anti-inflammatory properties beyond its well-established anticoagulant effects however, these remain poorly characterized. The effects of FXa inhibition on the generation of circulating extracellular vesicles (EV) are currently unknown. We hypothesize that circulating proinflammatory EV profiles differ in patients treated with rivaroxaban compared to those treated with warfarin and that these changes may represent a novel biomarker for cardioprotective effects mediated by FXa inhibition. Methods: Patients stably anticoagulated with 20 mg Rivaroxaban (n=15) once daily or warfarin (n=15) (at a target INR of 2.0 - 3.0) who had commenced therapy no sooner than 3 months previously for VTE treatment or NVAF were recruited following informed consent at the Mater Misericordiae University Hospital, Dublin. Demographic and clinical data were collected including patient age, body mass index, smoking and alcohol history, medical comorbidities, white cell and platelet count, creatinine clearance, liver profile, medications, detailed indication for anticoagulation and time since last dose of medication. Patients receiving warfarin had a time in therapeutic range of &gt; 55% and had an INR within target range at the time of sampling. Exclusion criteria included severe renal impairment (creatinine clearance &lt; 30 ml/min), significant liver impairment, known proinflammatory conditions (including systemic lupus erythematosus, inflammatory bowel disease, rheumatoid arthritis), recurrent VTE, active malignancy, previous stroke or systemic inflammation, antiphospholipid syndrome, strong thrombophilia (eg antithrombin deficiency), individuals aged &lt; 18, patients receiving inhibitory CYP3A4 and P-glycoprotein medications or platelet inhibitors, bleeding or platelet function disorders, and thrombocytopenia (platelet count &lt; 150 x 109/ml) Total particle counts in platelet poor plasma were measured by Nanoparticle Tracking Analysis (NTA) and flow cytometry. NTA was carried out using a NanoSight NS300 (Malvern) with a camera level of 13 and a detection threshold of 10. 15 x 60 second videos were captured per sample. Flow Cytometry analysis was performed using a CytoFlex LX (Beckman Coulter). Gigamix beads (Biocytex) were used to establish size gates for 100, 300, 500 and 900 nm particles. Samples were analysed in triplicate. Statistical analysis was performed in RStudio (version 1.2.1335) using a two-tailed t-test with a significance level of 5%. Results and Conclusion: Overall, we observed lower circulating EV levels in patients anticoagulated with FXa inhibitors versus vitamin K antagonists (Figure 1). Within our groups, patients with NVAF exhibited overall lower EV particle counts than VTE patients. Interestingly, EV levels were observed to be further diminished in patients treated with rivaroxaban versus warfarin. In this group, we detected a 2.5-fold decrease in the level of circulating EVs in patients with NVAF (1.18x1011±5.03x1010 particles/mL vs 2.92x1011±2.08x1011 particles/mL, p=0.039) and a 1.7-fold decrease in patients with VTE (3.37x1011±2.46x1011 particles/mL vs 5.71x1011±1.471011 particles/mL, p=0.164), in contrast to warfarin treatment. Collectively, these data suggest that FXa inhibition reduces the generation of circulating EVs, independent of the disease. These findings are of translational relevance towards characterizing cardioprotective mechanisms associated with rivaroxaban therapy. Disclosures Ni Ainle: Leo Pharma: Research Funding; BMS: Membership on an entity's Board of Directors or advisory committees; Actelion: Research Funding; Bayer: Membership on an entity's Board of Directors or advisory committees, Research Funding; Boehringer: Membership on an entity's Board of Directors or advisory committees; Daiichi Sankyo: Membership on an entity's Board of Directors or advisory committees. Maguire:Bayer: Research Funding; Leo Pharma: Research Funding; Actelion: Research Funding.

Outcomes associated with under-dosing of rivaroxaban for management of non-valvular atrial fibrillation in real-world Japanese clinical settings

The approved dose of oral anticoagulant rivaroxaban for patients with non-valvular atrial fibrillation (NVAF) in Japan is 15 mg once daily (od) in patients whose creatinine clearance is ≥ 50 mL/min, but recent real-world studies have demonstrated that these patients often received less than the recommended dose due to bleeding concerns. The effect of under-dosing on safety and effectiveness outcomes remains unclear. We used 1-year follow-up data from the XAPASS, a real-world Japanese prospective, single-arm, observational study. Of the 11,308 patients, 6521 patients who completed a 1-year follow-up and had a creatinine clearance ≥ 50 mL/min were included in this sub-analysis. Primary endpoints were any bleeding and a composite of stroke/non-central nervous system systemic embolism (non-CNS SE)/myocardial infarction (MI). Among the 6521 patients, 4185 (64.2%; mean CHADS2 score: 1.8) received the 15 mg od (recommended dose), whereas 2336 (35.8%; mean CHADS2 score: 2.3) received 10 mg od (under-dose). After adjusting for patient characteristics by propensity scoring and inverse probability of treatment weighting, incidence rates of major bleeding were comparable between under-dosed patients and patients who received the recommended dose (1.34 vs. 1.63 events/100 patient-years, p = 0.197), although the incidence rates of stroke/non-CNS SE/MI were higher in under-dosed patients than in those who received the recommended dose (2.15 vs. 1.48 events/100 patient-years, p = 0.009). In Japanese clinical practice, some NVAF patients receive rivaroxaban doses inconsistent with the recommendation. Considering the total clinical benefit, the recommended dose may be preferable in terms of balance of safety and effectiveness.Clinicaltrials.gov NCT01582737.

The Association Between the Use of Antiarrhythmic Drugs in Non-Valvular Atrial Fibrillation and Patient Prognosis Using Data from the China Atrial Fibrillation (China-AF) Registry.

BackgroundResults of the landmark Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM) trial comparing rhythm control and rate control strategies has led to dramatic changes in the pharmacological management of non-valvular atrial fibrillation (NVAF) patients. We sought to investigate the effect of antiarrhythmic drugs (AADs) on the clinical outcomes of NVAF patients using “real-world” data from China.Material/MethodsWe evaluated the association between AAD usage and clinical outcomes using clinical data of 8161 NVAF patients who were AAD-naive before enrollment in the China Atrial Fibrillation Registry, recruited between August 2011 and February 2017. The primary outcome was all-cause mortality.ResultsCompared with 6167 patients who never used any AADs, 1994 patients in the AAD group had lower incidence (per 100 person-years) of all-cause mortality (1.44 versus 3.91), cardiovascular death (0.45 versus 2.31), ischemic stroke (1.36 versus 2.03), and cardiovascular hospitalization (9.83 versus 10.22) over a mean follow-up duration of 316.7±90.4 days. After adjusting for potential confounders, AAD usage was associated with a lower risk of all-cause mortality [hazard ratio (HR): 0.50, 95% confidence interval (CI): 0.31–0.81] and decreased risk of cardiovascular death (HR: 0.30, 95% CI: 0.13–0.68). Subgroup analysis revealed AAD was associated with higher risk of cardiovascular hospitalization among female patients.ConclusionsAAD usage was associated with lower risk of 1-year all-cause mortality and cardiovascular death in “real-world” patients with NVAF.

PCV84 PHYSICIAN AND PATIENT PERCEPTIONS REGARDING CARE TRANSITIONS, ORAL ANTICOAGULANT TREATMENT AND MANAGEMENT OF NON-VALVULAR ATRIAL FIBRILLATION

To better understand challenges pertaining to care transitions, oral anticoagulant (OAC) treatment and management of non-valvular atrial fibrillation (NVAF) from the viewpoints of physicians and patients. Two surveys were conducted: one targeting 400 physicians who manage NVAF patients and the second targeting 400 NVAF patients. Physicians (cardiologists [C’s] and primary care physicians [P’s]) who treated NVAF patients were identified from medical claims in the HealthCore Integrated Research Database submitted between 3/1/14–3/31/16. Patients were identified from medical claims submitted between 4/1/15–3/31/16. Physician surveys assessed OAC treatment decision approaches and referral management strategies while patient surveys classified respondents according to self-reported OAC use and assessed perceptions around NVAF diagnosis, treatment and setting. Of 426 physicians (137 C’s; 289 P’s), 57% were in practice >20 years. C’s and P’s differed in OAC treatment philosophies and perceptions of management strategies: 84% C’s and 62% P’s assessed stroke risk prior to recommending OACs; 54% C’s reported co-managing patients with P’s vs 89% P’s reporting co-management with C’s. Of 398 NVAF patients, 25 never used OACs, 49 were prior only users and 324 were current users. Current OAC nonusers (never and prior usersn=74) differed from current users (n=324) in terms of AF diagnosis setting; 46% of current nonusers vs 31% of current users reported diagnosis in an emergency room. Among OAC never users, 40% reported treatment was never discussed. C‘s and P’s had perceived differences related to co-management of NVAF patients. High rates of NVAF diagnosis in acute care settings could result in gaps in transitions of care, particularly related communication about disease state and medication management. Further, the lack of discussions about NVAF treatments between physicians and patients may impact treatment initiation. Opportunities exist to target quality improvement interventions in NVAF patient co-management and transitions of care.

Anticoagulation in the early phase of non-valvular atrial fibrillation-related acute ischemic stroke: where do we stand?

The balance between the risk of early stroke recurrence and hemorrhagic transformation represents the cornerstone of practical management of non-valvular atrial fibrillation (NVAF)-related acute ischemic stroke (AIS). Patients who receive antithrombotic therapy as secondary prevention in the early phase of NVAF-related AIS have a better prognosis compared with patients who do not receive antithrombotic treatment. Recently, the RAF study showed that the best efficacy/safety profile was associated with anticoagulation started between 4 and 14 days from stroke onset. Based on the RAF study, the 2018 American Heart Association/American Stroke Association (AHA/ASA) guidelines suggest starting anticoagulants between 4 and 14 days from stroke onset with a class of recommendation IIa. Strong evidence for the use of direct oral anticoagulants (DOACs) in the early phase of NVAF-related AIS is lacking, because this kind of patients were excluded from phase III randomized clinical trials (RCT) and ad hoc RCTs are ongoing. However, the real life evidence suggests that early starting time of DOACs in patients with NVAF-related AIS is safe and associated with low recurrence risk and all-cause mortality. In the present review the Authors provide an update on anticoagulation in the early phase of NVAF-related AIS with focus on DOACs.

El método AMFE (Análisis Modal de Fallos y Efectos) aplicado a la anticoagulación de pacientes con fibrilación auricular no valvular

ObjectivesTo contribute to the improvement of the process of anticoagulation in patients with nonvalvular atrial fibrillation (NVAF) through awareness and training activities for Primary Care Physicians. Materials and methodsA total of 38 focus groups, sequenced according to an adaptation of the Failure Mode and Effects Analysis (FMEA) method. Each meeting was driven by «brainstorming» methodology. The geographical representation was homogeneous, with a total of 482 national.physicians (444 Primary Care Physicians, and 38 cardiologists). The meetings were held between March 28 and June 20, 2017. ResultsThe main unsafe actions that can lead to a haemorrhagic or thrombotic event are incorrect anticoagulation or lack of patient follow-up. These events are mainly caused by training deficiencies in the management of NVAF, or by not taking into account possible interactions with vitamin K antagonist drugs. The main recommendations to alleviate these failures were focused on a good follow-up of patients with NVAF, on creating or updating the protocols or clinical practice guidelines, and on promoting the continuous training of physicians who usually manage patients with non-valvular AF treated with oral anticoagulants. ConclusionsA significant percentage of patients with NVAF are not correctly anticoagulated. Specific actions are required to alleviate this problem. Among them, the importance of a general anticoagulation training was emphasised, and particularly, the use of direct oral anticoagulants.