Stroke Prevention In Non-valvular Atrial Fibrillation Research Articles

Choosing Appropriate Candidates for Left Atrial Appendage Occlusion.

Atrial fibrillation (AF) is one the most prevalent arrhythmias globally and is associated with a significantly higher risk of morbidity and mortality, including an up to five-fold increase in risk of stroke. While oral anticoagulation therapy remains the standard approach for stroke prevention in nonvalvular AF, left atrial appendage occlusion (LAAO) has emerged as a viable alternative for patients who are intolerant to long-term oral anticoagulation therapy. However, selecting appropriate candidates for LAAO requires a comprehensive evaluation that considers various clinical factors, although this presents a challenge in clinical practice. This review aims to provide an overview of the current recommendations for patient selection in LAAO procedures and the key factors that need to be considered both before and after the procedure, as well as the ongoing advancements in this field that may facilitate the selection of patients for LAAO.

Comprehensive systematic review and meta-analysis on anticoagulants and aspirin for stroke prevention in non-valvular atrial fibrillation patients.

Non-valvular atrial fibrillation (NVAF) is a common manifestation of cardiac arrhythmia, whose significance is heightened in the context of an aging global population and changing lifestyles, leading to an increased incidence. Stroke prevention in NVAF is a complex challenge that requires a comprehensive exploration of interventions. The emergence of Direct Oral Anticoagulants (DOACs) is a potential treatment, necessitating a thorough evaluation of their safety and efficacy. As the quest for the best strategy for thrombotic risk in these patients continues, the interaction between DOAC and aspirin has become the focus of research. With a rigorous methodological approach, we conducted a thorough search of scientific databases up to August 2023. The methodology involved meticulous screening, careful data extraction, and rigorous assessment of trial quality, all conducted by two independent investigators. The results were synthesized through standardized mean differences, accompanied by 95% confidence intervals. DOACs demonstrated significant enhancements in stroke prevention for NVAF, which was indicated by favorable outcomes in bleeding (RR = 4.04, 95% CI: 3.96, 4.12), coronary artery disease (RR = 2.45, 95% CI: 2.42, 2.48), mortality (RR = 0.49, 95% CI: 0.43, 0.56), myocardial infarction (RR = 1.85, 95% CI: 1.81, 1.88), and stroke (RR = 1.50, 95% CI: 1.47, 1.54). Notably, DOACs demonstrated optimal efficacy for NVAF patients with stroke. DOACs may be potentially effective for preventing stroke after NVAF.

Edoxaban Anticoagulation in Atrial Fibrillation: Real-World Data and Evidence.

Atrial fibrillation (AF) and stroke are two prevalent health conditions with many shared risk factors. Over the past two decades, non-vitamin K antagonist oral anticoagulants (NOACs) have emerged as important alternatives to vitamin K antagonists, owing to their efficacy, safety profile, and the absence of a need for frequent international normalized ratio monitoring. Introduced as the most recent NOAC, edoxaban has been approved for stroke prevention in non-valvular AF in numerous countries since 2014. The pivotal phase III Effective Anticoagulation with Factor Xa Next Generation in Atrial Fibrillation-Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48) trial demonstrated that edoxaban is as efficacious as warfarin in preventing strokes and systemic embolic events. Furthermore, it is linked to reduced rates of major, life-threatening, intracranial, major, or clinically relevant non-major bleeding events and decreased cardiovascular mortality in AF when compared to warfarin. Growing data highlights the utilization of edoxaban in treating AF patients in clinical settings. This article provides an overview of real-world evidence regarding edoxaban's use in preventing stroke and systemic embolic events in AF patients, emphasizing the concerns that physicians factor into their clinical decision-making.

Oral Anticoagulants and the Risk of Dementia in Patients With Nonvalvular Atrial Fibrillation: A Population-Based Cohort Study.

Nonvalvular atrial fibrillation (NVAF) is associated with an increased risk of dementia. Oral anticoagulants (OACs) are essential for stroke prevention in NVAF, and studies have shown a possible protective effect on dementia. However, findings have been inconsistent and hampered by methodological limitations. Thus, we assessed whether the use of OACs is associated with a decreased incidence of dementia in patients with NVAF. In addition, we explored the impact of the cumulative duration of OAC use on the incidence of dementia. Using the UK Clinical Practice Research Datalink, we formed a cohort of all patients aged 50 years or older with an incident diagnosis of NVAF between 1988 and 2017 and no prior OAC use, with a follow-up until 2019. Patients were considered unexposed until 6 months after their first OAC prescription for latency considerations and exposed thereafter until the end of follow-up. We used time-dependent Cox regression models to estimate hazard ratios (HRs), adjusted for 54 covariates, with 95% CIs for dementia associated with OAC use, compared with nonuse. We also assessed whether the risk varied with the cumulative duration of OAC use, compared with nonuse, by comparing prespecified exposure categories defined in a time-varying manner and by modeling the HR using a restricted cubic spline. The cohort included 142,227 patients with NVAF, with 8,023 cases of dementia over 662,667 person-years of follow-up (incidence rate 12.1, 95% CI 11.9-12.4 per 1,000 person-years). OAC use was associated with a decreased risk of dementia (HR 0.88, 95% CI 0.84-0.92) compared with nonuse. A restricted cubic spline also indicated a decreased risk of dementia, reaching a low at approximately 1.5 years of cumulative OAC use and stabilizing thereafter. Moreover, OAC use decreased the risk in patients aged 75 years and older (HR 0.84, 95% CI 0.80-0.89), but not in younger patients (HR 0.99, 95% CI 0.90-1.10). In patients with incident NVAF, OACs were associated with a decreased risk of dementia, particularly in elderly individuals. This warrants consideration when weighing the risks and benefits of anticoagulation in this population. This study provides Class II evidence that in patients with NVAF, OAC use (vs nonuse) is associated with a decreased risk of dementia.

Tolerability and Efficacy of Rivaroxaban Versus Warfarin for Non Vulvular Atrial Fibrillation

Introduction: Atrial fibrillation (AF) is the most widespread chronic heart arrhythmia, affecting 1–2 % of the general population. Objectives: Patients with non-valvular atrioventricular fibrillation are the major focus of this research. Rivaroxaban is compared against warfarin in terms of tolerability and efficacy. Material and methods: This cross sectional comparative study was conducted in Pakistan Institute of Medical Sciences Islamabad during January 2020 till December 2020. A total of 120 OPD patients who satisfied the study's inclusion and exclusion criteria were included in the research after it was given the green light by the hospital's ethics committee. A complete medical history and physical examination were required to ensure that all participants met the criteria for inclusion. It was determined that obtaining express written consent was essential. Results: As indicated above, 15 individuals were removed from the study; six patients in the NOAC group refused to participate and departed the study; while four patients were lost to follow-up. In this study, rivaroxaban was administered to twenty-one participants, whereas warfarin was administered to the remaining twenty-four. Conclusion: Oral anticoagulants for stroke prevention in non-valvular AF have advanced in development, benefiting patients and clinicians alike with fewer medication and food interactions, no monitoring need, and a wider therapeutic index.

Minimally invasive thoracoscopic left atrial appendage occlusion compared with transcatheter left atrial appendage closure for stroke prevention in recurrent nonvalvular atrial fibrillation patients after radiofrequency ablation: a prospective cohort study.

BACKGROUNDTanscatheter left atrial appendage (LAA) closure and minimally invasive thoracoscopic LAA occlusion are local interventions of LAA for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF). However, the safety and efficacy of these methods have not been compared. This prospective cohort study aimed to assess the safety and efficacy of those two treatment approaches for stroke prevention in NVAF patients.METHODSTwo hundred and nine recurrent NVAF patients who received radiofrequency ablation were enrolled. These patients were treated with transcatheter LAA closure or thoracoscopic LAA occlusion. The patients were followed up from the first postoperative day and evaluated for efficacy endpoints (stroke/transient ischemic attack (TIA), systemic embolism (SE), and death) and a safety endpoint (bleeding events). Perioperative complications were recorded.RESULTSAfter a median follow-up of 1.8 years (383 patient-years), the overall rate of the composite efficacy endpoints was similar between the two groups (3.8 vs. 2.7 events per 100 patient-years; HR = 0.71; 95% CI: 0.225−2.237; P = 0.559). However, regarding primary safety endpoint, there were 1.5 bleeding events per 100 patient-years in the thoracoscopic LAA occlusion group, compared with 6.4 in transcatheter LAA closure group (HR = 0.246; 95% CI: 0.074−0.819; P = 0.022). The incidence of operative complications was 3/138 (2.17%) in thoracoscopic LAA occlusion group and 1/71 (1.41%) in transcatheter LAA closure group. CONCLUSIONSThoracoscopic LAA occlusion and transcatheter LAA closure have similar efficacy in preventing stroke in NVAF patients. However, the thoracoscopic group had fewer bleeding events than the transcatheter group, but the former group required a longer hospital stay.

From a DOAC to Warfarin: Reasons Why Patients Switch

1. IntroductionThe introduction of direct oral anticoagulants (DOACs) has led to their widespread use for stroke prevention in patients with non-valvular atrial fibrillation (AF) and as first-line treatment in acute venous thromboembolism (VTE), and also as secondary thromboprophylaxis in patients with a history of VTE. In addition, many patients previously taking vitamin K antagonists (VKAs) have switched to a DOAC for reasons including erratic international normalised ratio (INR) control, medication interactions, convenience, possible lower major bleeding risk and possible improved stroke prevention rates. Although DOACs are well tolerated, little is known about the numbers of patients switching from a DOAC to (or back to) a VKA or the reasons for doing so.2. MethodsThis study was an analysis of prospectively-collected data from a four-year period surveying a computer-based VKA (warfarin) dose adjustment clinic in a large city centre hospital. The primary objective was to identify the reasons for patients switching from a DOAC to warfarin. Secondary objectives included assessing indication for anticoagulant therapy and choice of DOAC. The time in therapeutic range (TTR) once switched back to VKA and clinical events following commencement of warfarin were also determined.3. ResultsIn our VKA clinic with 1791 patients annually under review, 39 patients were identified as having switched from a DOAC to warfarin. The mean age of the patients was 68.5 years +/- 13.8 and the majority (N=24) were female. AF was the most common condition necessitating anticoagulation (N=24); VTE accounted for 12 cases; arterial thromboembolism (N=2) and cardiac thrombus (N=1) were less common causes and one patient had been started on a DOAC in the setting of valvular replacement. Of the patients who were switched to warfarin, seven (17.9%) had originally been anticoagulated with a VKA prior commencing on a DOAC. In terms of anticoagulant choice, the majority of patients (N = 27) were taking rivaroxaban with 6 patients each on dabigatran and apixaban. The causes for switching in this cohort are outlined in table 1. Interesting cases of note include one patient who had a splenic infarction while taking rivaroxaban for atrial fibrillation and one patient who developed a new thumb arterial embolus while taking rivaroxaban for a PE.Following warfarin commencement, there was a total of eight clinical events reported (21.1% of patients). There were seven bleeding events recorded with two serious events necessitating hospital admission and five minor events; in five of these (71.4%), the original reason for switching back to warfarin had been a bleed while on a DOAC. One further patient had a high INR necessitating administration of vitamin K. The mean TTR of this cohort was 61.4% +/- 22.3. 33 patients (84.6%) of patients still attend the warfarin clinic, with cessation of anticoagulant therapy having occurred in three patients (7.7%) and death occurring in one patient (2.6%); two patients (5.1%) have been recommenced on a DOAC.4. DiscussionDOACs have several advantages over warfarin for many patients; they do not require monitoring and the dose remains stable. Index trials have demonstrated at least non-inferiority to warfarin in stroke prevention in non-valvular AF and treatment of VTE, with at least no significant difference in bleeding outcomes. However, warfarin can be an attractive option in complicated cases as it can be rapidly reversed, and there continues to be greater levels of clinician experience with its use. In the present study, we report data regarding the switch back to warfarin in a DOAC cohort, an area into which little research has been conducted. There were only 39 patients reported over a four-year period; this represents only a small minority of the full cohort. As expected, the majority of patients required a switch because of re-thrombosis or a bleeding event. Patients also required an appropriate switch in situations outside of the licence of the DOACs i.e. renal deterioration or valvular AF. The authors are not aware of any data regarding arterial embolisation in rivaroxaban users, and acute hepatitis has been rarely described in rivaroxaban use. These data confirm that switching from a DOAC to warfarin is seldom deemed necessary by clinicians. However, familiarity and experience may guide therapy in complicated cases, and vigilance is required to ensure adherence to the licence when prescribing a DOAC. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Direct oral anticoagulant use in special populations.

The pivotal phase III trials demonstrating efficacy and safety of direct oral anticoagulants (DOACs) in the treatment of venous thromboembolism (VTE) or nonvalvular atrial fibrillation (NVAF) excluded patients with important and common comorbidities, including obesity, advanced chronic kidney disease, cirrhosis, cancer and antiphospholipid antibody syndrome. Despite the lack of large prospective randomized control trials in these patient populations, the use of DOACs has led to a wealth of efficacy and safety data within these groups. Retrospective studies, meta-analyses, national databases and pharmacokinetic data have shed light on the efficacy and safety of DOACs in these patient populations. Although DOACs should be avoided in those with high-risk triple positive antiphospholipid antibody syndrome, advanced cirrhosis, advanced kidney disease and intact gastrointestinal cancers, and used with caution in genitourinary cancers, their use extends beyond the inclusion criteria of the initial randomized control trials. DOACs have revolutionized anticoagulant management and have become the cornerstone for VTE treatment and stroke prevention in NVAF. The decision to use DOACs must be individualized. Patient preference, underlying comorbidities and informed consent must always be considered when selecting the most appropriate anticoagulant.

Patients’ perspectives on factors affecting their involvement in decision-making on oral anticoagulant therapy for stroke prevention in non-valvular atrial fibrillation

Abstract Introduction Acknowledging patients’ preferences and addressing their concerns is thought to improve patients’ satisfaction with consultations, resulting in improved adherence and health benefits [1]. Adherence to oral anticoagulant (OA) therapy in non-valvular atrial fibrillation (NVAF) is crucial to prevent AF-related strokes. Previous research on anticoagulation in NVAF indicated that decision-making was dominated by prescribers, but patients offered several therapy options reported being involved [2]. Identifying the patient’s perspective on factors affecting their involvement could help to deliver more patient-centred care in the management of AF. Aim To explore patients’ perspectives and experiences concerning factors affecting their involvement in decision-making about OA therapy for stroke prevention in NVAF. Methods Semi-structured face-to-face interviews were conducted with patients in three health economies in the North of England between August 2018 and April 2019. An interview topic guide based on narrative review findings [2] was developed and refined by a Patient and Public Involvement (PPI) group to ensure clarity. Theoretical sampling was used to recruit adults (>18 years) diagnosed with NVAF, prescribed OA (vitamin K antagonist or direct oral anticoagulant (DOAC)), and able to give written consent. Up to 30 potential participants were approached by a member of their direct care team (nurse or pharmacist) in secondary and primary care anticoagulation or arrhythmia clinics. PPI members recruited patients from a local patient support group. Data collection continued until data saturation was achieved. Audio recorded interviews were transcribed verbatim and analysed using the Framework method. Results A total of 21 patient with median (IQR) age of 73 years (65–78 years) were interviewed. Eleven patients took DOACs. The median (IQR) time of taking OA was 3 years (4 weeks-7 years), warfarin 7 years (3–9 years) and DOAC 1 year (4 weeks-4 years). Interviews lasted between 15 and 48 minutes (average 27 minutes). Three themes were identified during analysis (Figure 1). Patients described therapy decisions being made by just the clinician, jointly with the clinician, and in few cases by the patient alone. The lack of involvement resulted from patients perceiving that there was only a choice between accepting and refusing the therapy, and clinician’s role was to make decisions. Limited consultation times, lack of continuous relationship with a clinician and knowledge about OAs options discouraged patients from being involved and some patients reported difficulties with the prescribed therapy. Patients that were involved considered safety of therapy options and impact on daily life. Conclusions Limited consultation time, patient’s perception of clinician’s role, quality of patient-clinician relationship, and patients’ awareness of therapy options were main factors influencing the level of patient involvement in the decision-making. Support from both organisation and clinicians (e.g., longer consultations, availability of different therapy options) is needed to facilitate greater patient involvement, which could prevent difficulties encountered by some patients. The main strength of this study was recruitment of participants from three health economies differing in anticoagulation service provision models, which enabled greater insight into potential barriers. However, the sample was lacking ethnic diversity and could have potential of recall bias.

ROLE OF NOVEL ORAL ANTICOAGULANTS (NOACS)IN PATIENTS WITH ATRIAL FIBRILLATION CARDIOVERSION- AN EXECUTIVE SUMMARY

In patients with non-valvular atrial fibrillation (NVAF), oral anticoagulation is necessary for prevention of stroke and systemic embolism especially during cardioversion. While Vitamin K antagonists (VKAs) have historically been the standard of care, these medications are limited by numerous food and drug interactions with requirements for frequent monitoring (INR) and dose adjustments. Over the past decade, several novel oral anticoagulants (NOACs) have been developed to directly inhibit factor IIa/thrombin (dabigatran) or activated factor X (apixaban, rivaroxaban, edoxaban). These medications have been shown to be at least as effective as warfarin for stroke prevention in NVAF with more favorable safety profiles. However, their advantages are underscored by a lack of specific antidotes and assays quantifying their anticoagulant effects. This review addresses how well do the Rivaroxaban prevents stroke and systemic embolism compare to VKAs in patients with NVAF, with a special focus on high-risk populations, including the elderly, those with renal disease, diabetes mellitus, coronary artery disease, and previous stroke.

ROLE OF NOVEL ORAL ANTICOAGULANTS (NOACS)IN PATIENTS WITH ATRIAL FIBRILLATION CARDIOVERSION- AN EXECUTIVE

In patients with non-valvular atrial fibrillation (NVAF), oral anticoagulation is necessary for prevention of stroke and systemic embolism especially during cardioversion. While Vitamin K antagonists (VKAs) have historically been the standard of care, these medications are limited by numerous food and drug interactions with requirements for frequent monitoring (INR) and dose adjustments. Over the past decade, several novel oral anticoagulants (NOACs) have been developed to directly inhibit factor IIa/thrombin (dabigatran) or activated factor X (apixaban, rivaroxaban, edoxaban). These medications have been shown to be at least as effective as warfarin for stroke prevention in NVAF with more favorable safety profiles. However, their advantages are underscored by a lack of specific antidotes and assays quantifying their anticoagulant effects. This review addresses how well do the Rivaroxaban prevents stroke and systemic embolism compare to VKAs in patients with NVAF, with a special focus on high-risk populations, including the elderly, those with renal disease, diabetes mellitus, coronary artery disease, and previous stroke.

Real-world study of direct oral anticoagulant dosing patterns in patients with atrial fibrillation

Direct oral anticoagulants (DOACs) are preferred for stroke prevention in atrial fibrillation (AF). However, off-label doses have been associated with increased risk of adverse events. The objective of this study was to compare the frequency and outcomes of labeled versus off-label DOAC dosing in patients with AF. This retrospective cohort study included adults diagnosed with nonvalvular AF (NVAF), discharged from University of Utah Health on DOAC therapy between 7/1/2017 and 9/30/2017. The primary outcome was off-label DOAC dosing frequency, defined as dosing inconsistent with manufacturer labeling. Secondary outcomes included variables associated with off-label dosing and a composite of adverse events (major bleeding, thromboembolism, and all-cause mortality) in the 90 days following the index hospital discharge. Of 249 included patients, 16.1% were discharged with off-label dosing. Factors associated with off-label dosing included advanced age, lower body mass index, decreased renal function, use of rivaroxaban, and hepatic impairment. The majority of off-label patients (70%) received lower-than-recommended DOAC dosing. Prescriber rationale for off-label prescribing was documented in 25% of patients and included anti-Xa guided dosing, high risk for bleeding or thromboembolism, and prior history of on-therapy adverse events. The rate of adverse events between labeled and off-label DOAC doses was not statistically different (10.0% vs. 6.7%, p=0.299), although this is likely due to small sample size. Off-label DOAC prescribing for stroke prevention in NVAF at University of Utah Health was consistent or lower than previously published studies. Off-label dosing most often involved under-dosing of rivaroxaban. Future research should investigate the role of provider rationale and insight in optimizing DOAC therapy outcomes.

PCV78 BURDEN OR ATRIAL FIBRILLATION AND BUDGET IMPACT OF DABIGATRAN IN ALGERIA

Atrial fibrillation (AF) is the most common cardiac arrhythmia. It is associated with an increased risk of thromboembolic and cerebral complications, significantly impacting public health. In Algeria for instance, where only vitamin-K agonists (VKA) are reimbursed, stroke is a leading cause of mortality, representing 15.6% of all deaths in 2012. The present study aimed to estimate the clinical and economic burden of non-valvular AF (NVAF) and whether dabigatran could help address it. We first reviewed literature to identify the epidemiological burden of the disease. Next, six hospital centres and one private clinic were surveyed on consumed resources and unit costs for treatment and management of stroke prevention in NVAF and associated complications. Results were then combined with event probabilities from the RE-LY trial in an economic model to estimate the annual cost of NVAF prevention and complications for the Algerian healthcare system, and the potential impact of introducing dabigatran. Epidemiology data suggest 187,686 patients suffer from NVAF in Algeria. 70% were treated with VKA, with an annual direct medical cost of €59.1M (€548 average per patient), distributed as: €1.12M drug costs (2.0%), €1.44M INR monitoring (2.4%), €38.7M hospitalisation costs (65.5%) and €17.8M 1-year post-discharge costs (30.1%). Even though only 47.6% of patients were uncontrolled, they represented 82.9% of clinical events (41,055) and 81.6% of costs (€48.2M). The introduction of dabigatran in this uncontrolled population could avoid 34,453 events (-83.9%), 5,867 deaths (-85.1%) per year, and despite a drug cost increase of €37.0M, it could decrease total costs by 7.7% to €44.5M. The absence of therapeutic alternatives in Algeria for uncontrolled patients places a significant clinical and economic burden on the healthcare system, mostly through hospital costs. Dabigatran showed a potential to reduce the number of clinical events and deaths, freeing up hospital resources and generating moderate savings on healthcare budgets.

458Real world persistence with direct oral anticoagulants in anticoagulation naive patients with atrial fibrillation

Abstract Introduction Anticoagulation therapy is central for the management of stroke in patients with non-valvular atrial fibrillation (NVAF). Persistence with oral anticoagulation is essential to prevent thromboembolic complications. Purpose To assess persistence levels of DOACs and look for possible predictors of treatment discontinuity in NVAF patients. Methods We performed a population-based retrospective cohort study in the Veneto Region (north-eastern Italy, about 5 million inhabitants) using the regional health system databases. Naïve patients initiating direct oral anticoagulants (DOACs) for stroke prevention in NVAF from July 2013 to September 2017 were included in the study. Patients were identified using Anatomical Therapeutic Chemical (ATC) codes, excluding other indications for anticoagulation therapy using ICD-9CM codes. Treatment persistence was defined as the time from initiation to discontinuation of the therapy. Baseline characteristics and comorbidities associated to the persistence of therapy with DOACs were explored by means of Kaplan-Meier curves and assessed through Cox regression. Results Overall, 17920 patients initiated anticoagulation with DOACs in the study period. Most patients were older than 74 years old, while gender was almost equally represented. Comorbidities included hypertension (72%), diabetes mellitus (17%), congestive heart failure (9%), previous stroke/TIA (20%), and prior myocardial infarction (2%). After one year, the persistence to anticoagulation treatment was 82.7%, while the persistence to DOAC treatment was 72.9% with about 10% of the discontinuations being due to switch to VKAs. On multivariate analysis, factors negatively affecting persistence were female gender, younger age (<65 years), renal disease and history of bleeding. Conversely, persistence was better in patients with hypertension, previous cerebral ischemic events, and previous acute myocardial infarction. Persistence to DOAC therapy Conclusion This real-world data show that within 12 months, one out of four anticoagulation-naïve patients stop DOACs, while one out of five patients stop anticoagulation. Efforts should be made to correct modifiable predictors and intensify patient education.

Real-world persistence with direct oral anticoagulants (DOACs) in naïve patients with non-valvular atrial fibrillation

BackgroundAnticoagulation therapy is central for the management of stroke in patients with non-valvular atrial fibrillation (NVAF). Persistence with oral anticoagulation is essential to prevent thromboembolic complications. MethodsWe performed a population-based retrospective cohort study in the Veneto Region (north-eastern Italy, about 5 million inhabitants) using the regional health system databases. Naïve patients initiating direct oral anticoagulants (DOACs) for stroke prevention in NVAF from July 2013 to September 2017 were included in the study. Patients were identified using Anatomical Therapeutic Chemical (ATC) codes, excluding other indications for anticoagulation therapy using ICD-9CM codes. Treatment persistence was defined as the time from initiation to discontinuation of the therapy, including any therapeutic switching among DOACs. Baseline characteristics and comorbidities associated to the persistence of therapy with DOACs were explored by means of Kaplan-Meier curves and assessed through Cox regression. ResultsNaïve patients initiating direct oral anticoagulants for stroke prevention in NVAF identified in a 4.25-year period are 17,920. After one year, the persistence to the DOACs is 72.9%. Approximately 9.8% of the discontinuations are due to switch to vitamin k antagonists (VKAs). On multivariate analysis, factors negatively affecting persistence were female gender, age <65 years, renal disease and history of bleeding. On the other hand, persistence was better in patients with hypertension, previous cerebral ischemic events, and previous acute myocardial infarction. ConclusionIn this study of real world data, one out four naive patients stopped treatment with DOACs within 12 months. Some characteristics may identify patients with poor persistence.

Cost of Anticoagulation for Non-Valvular Atrial Fibrillation in Australia

Objectives: Since 2013, non-vitamin K antagonist oral anticoagulants (NOACs) have surpassed Warfarin to become the mainstay treatment of non-valvular atrial fibrillation (AF) in Australia. We examine the analogous change in cost of anticoagulation over the past 5 years. Methods: Data were extrapolated from the Pharmaceutical Benefits Scheme (PBS) and Medicare Australia. We examined the total number of scripts and cost of Warfarin and all NOACs- Apixaban, Rivaroxaban, Dabigatran- that were available for non-valvular AF from September 2013 until October 2018. Month-to-month comparisons were made between the cost of all NOACs and Warfarin. INR testing cost was examined over the same period. Results: NOAC prescription in Australia has continued to rise with a 3530% increase from September 2013 to October 2018 corresponding to a 42.8% decline in Warfarin use. Our study further demonstrates a 31.9% decrease in INR testing. Apixaban has now exceeded Rivaroxaban as the most commonly prescribed NOAC (48.2% vs. 40.4%) for non-valvular AF. With the increasing use of NOACs, cost has also increased proportionately by 3400% from $790,569 in September 2013 to $26,902,194 in October 2018. This has corresponded with a 21.9% decrease in cost of Warfarin and INR testing from $7,493,898 to $5,855,804. Conclusions: NOACs have become the drugs of choice for stroke prevention in non-valvular AF in Australia. While use of NOACs has increased cost to the government, cost of Warfarin and INR testing has declined and costs are expected to decrease further when NOAC patents expire in 2020.

Underuse of Vitamin K Antagonist and Direct Oral Anticoagulants for Stroke Prevention in Patients With Atrial Fibrillation: A Contemporary Review.

Atrial fibrillation (AF) is a leading cause of stroke. Oral anticoagulant (OAC) therapy can significantly reduce the risk of stroke in patients with AF, but underuse of OACs for stroke prevention continues to be a serious clinical problem, with significant deleterious impact on outcomes. We review the studies demonstrating OAC underutilization and evaluating strategies for promoting the increased use of OAC therapy for stroke prevention in nonvalvular AF (NVAF) patients, including in special patient populations.

Role of rivaroxaban in the management of atrial fibrillation: insights from clinical practice.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, and it leads to significant morbidity and mortality, predominantly from ischemic stroke. Vitamin K antagonists, mainly warfarin, have been used for decades to prevent ischemic stroke in AF, but their use is limited due to interactions with food and other drugs, as well as the requirement for regular monitoring of the international normalized ratio. Rivaroxaban, a direct factor Xa inhibitor and the most commonly used non-vitamin K oral anticoagulant, avoids many of these challenges and is being prescribed with increasing frequency for stroke prevention in non-valvular AF. Randomized controlled trial (RCT) data from the ROCKET-AF(Rivaroxaban once daily oral direct Factor Xa inhibition compared with vitamin K antagonism for prevention of stroke and embolism trial in atrial fibrillation) trial have shown rivaroxaban to be non-inferior to warfarin in preventing ischemic stroke and systemic embolism and to have comparable overall bleeding rates. Applicability of the RCT data to real-world practice can sometimes be limited by complex clinical scenarios or multiple comorbidities not adequately represented in the trials. Available real-world evidence in non-valvular AF patients with comorbidities – including renal impairment, acute coronary syndrome, diabetes mellitus, malignancy, or old age – supports the use of rivaroxaban as safe and effective in preventing ischemic stroke in these subgroups, though with some important considerations required to reduce bleeding risk. Patient perspectives on rivaroxaban use are also considered. Real-world evidence indicates superior rates of drug adherence with rivaroxaban when compared with vitamin K antagonists and with alternative non-vitamin K oral anticoagulants – perhaps, in part, due to its once-daily dosing regimen. Furthermore, self-reported quality of life scores are highest among patients compliant with rivaroxaban therapy. The generally high levels of patient satisfaction with rivaroxaban therapy contribute to overall favorable clinical outcomes.

Two-year follow-up of patients treated with dabigatran for stroke prevention in atrial fibrillation: Global Registry on Long-Term Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF) registry

GLORIA-AF is a large, global, prospective registry program of newly diagnosed atrial fibrillation (AF) patients with ≥1 stroke risk factors. We describe the effectiveness and safety of dabigatran etexilate over 2 years from routine clinical practice in nearly 3000 patients from GLORIA-AF who are newly diagnosed with non-valvular AF and at risk of stroke. Consecutive enrollment into phase II of GLORIA-AF was initiated following approval of dabigatran for stroke prevention in non-valvular AF. Within this Phase II, 2937 dabigatran patients completed 2-year follow-up by May 2016 and were eligible for analysis. Patients who took at least 1 dose of dabigatran (n=2932) were used to estimate incidence rates. Overall incidence rates per 100 person-years of 0.63 (95% confidence interval [CI], 0.42-0.92) for stroke, 1.12 (0.83-1.49) for major bleeding, 0.47 (0.29-0.72) for myocardial infarction, and 2.69 (2.22-3.23) for all-cause death were observed. For patients taking 150 mg dabigatran twice daily (BID), corresponding rates (95% CI) were 0.56 (0.30-0.94), 1.00 (0.64-1.47), 0.48 (0.25-0.83), and 2.07 (1.55-2.72), respectively. For patients taking 110 mg dabigatran BID, event rates (95% CI) were 0.67 (0.33-1.20), 1.16 (0.70-1.80), 0.43 (0.17-0.88), and 3.16 (2.36-4.15). These global data confirm the sustained safety and effectiveness of dabigatran over 2 years of follow-up, consistent with the results from clinical trials as well as contemporary real-world studies. • Non-vitamin K antagonist (VKA) anticoagulants (NOACs) are the preferred therapy for prevention of ischemic stroke based on phase 3 trials, but there is insufficient information on their efficacy and safety in daily practice, based on prospectively collected data. • This study shows that in non-valvular AF patient population, with up to 2 years of follow-up, the use of dabigatran led to a low incidence of ischemic stroke, major bleeding, and myocardial infarction in routine clinical care, confirming the sustained safety and effectiveness of dabigatran in clinical practice over 2 years of follow-up.

Abstract 13225: Which Oral Anti-Coagulant Do Patients Prefer for Stroke Prevention in Non-Valvular Atrial Fibrillation?

Introduction: There are various oral anticoagulants available for stroke prevention in patients suffering from non-valvular atrial fibrillation (NVAF) with some drug-related variations in clinical profile and non-clinical attributes. Patient preferences should be taken into account in anticoagulant prescription decisions. Hypothesis: Patient valuation of different anticoagulant characteristics in stroke prevention allows for meaningful comparison of the non-VKA oral anticoagulants (NOACs; apixaban, dabigatran, edoxaban, rivaroxaban) and Vitamin K Antagonist (VKA, ie. warfarin). Methods: Multi-criteria decision analysis was developed with 5 clinical and 3 non-clinical criteria. Criteria weights were defined using results from two discrete choice experiments (DCEs). The evaluation model contained more fine-grained events than the DCEs, and therefore preference weights from DCEs needed to be distributed to the evaluation criteria. The weights were distributed according to event fatality rates, which were obtained from the RE-LY trial that compared dabigatran to warfarin. An additive model was used to combine treatment performance with the weights to estimate the overall value of each oral anticoagulant. Probabilistic and structural sensitivity analyses were performed. Results: Dabigatran obtained the highest overall value (see Figure: weighted contribution of different evaluation criteria to the overall value of five oral anticoagulants) and the highest first rank probability (88%) in the probabilistic sensitivity analysis. Rivaroxaban performed worse than the other NOACs, but better than VKA (both with 0% first rank probability). The results were insensitive to removing availability of reversal agent from the model. Conclusions: Patient preferences on treatment characteristics allows to discriminate oral anticoagulants for stroke prevention in NVAF, with dabigatran ranking highest and warfarin lowest.