Stroke Prevention In Atrial Fibrillation Research Articles

Abstract 4141454: Atrial Fibrillation in American Indians: Comparative Analysis of Characteristics and Anticoagulation Use for Stroke Prevention of Atrial Fibrillation

Background: Atrial fibrillation (AF) is the most common cardiac arrhythmia in the United States, affecting individuals of all races. Anticoagulation (AC) therapy is recommended by the guidelines to reduce the risk of stroke in AF patients. Previous reports indicate that American Indians (AI) have a higher risk of AF and an increased risk of stroke from AF. Aim: To describe the demographic and clinical characteristics of the AI population with AF and compare their AC status with other racial groups. Methods: We retrospectively analyzed AF patients age >18 years hospitalized between January 2022 and October 2023 in two hospitals serving a large Navajo Nation AI population in rural Northern Arizona. We compared baseline characteristics, AC status and direct oral anticoagulant (DOAC) use between AI and other races. Between group statistical analysis was completed using a chi-square for categorical variables and a Mann-whiney U test for continuous variables, with statistical significance defined as a p-value ≤ 0.05. Results: In total, 9255 patients were admitted with AF: 871 (9.4%) were AI, with 696 (79.9%) being Navajo Nation AI and 8284 (89.5%) from other non-AI races. AI patients with AF were younger (average age 65±15.9 vs 75±11.2; p <0.0001), had fewer female patients (30.5% vs 39.3%; p <0.0001), and were less likely to be treated with oral anticoagulation (40.5% vs 50.9%; p <0.0001; OR 0.66; 95% CI: 0.57 to 0.76) compared to non-AI races (table 1). Among those anticoagulated, AI patients were less likely to receive a DOAC (38.0% vs 44.7%; p = 0.0002; OR 0.76; 95% CI: 0.66 to 0.88) compared to non-AI races (table 2). Conclusions: Our analysis, with a significant number of AI pts, reveal that AI patients develop AF at a younger age and despite an increased risk of stroke, have significantly lower rates of anticoagulation use, particularly with DOACs. Our findings underscore the need for guideline-adherent AC use in this AI population.

Abstract 4136743: Current Oral Anticoagulation Use Among Patients With Atrial Fibrillation and Risk Factors Associated With Inadequate Treatments: A Report From a UK Population Cohort Study

Background: The worldwide prevalence of atrial fibrillation (AF) continues to grow with approximately 60 million cases each year. Aim: To understand demographic and clinical attributes of patients receiving adequate DOAC (direct oral anticoagulant) treatment, DOAC undertreatments, or no OAC (oral anticoagulant) treatments, thus providing valuable perspectives into the current landscape of stroke prevention in AF within the UK. Methods: We used the Clinical Practice Research Datalink (CPRD) Aurum database from January 2020 to March 2021 for this retrospective observational study. Patients’ characteristics from various cohorts (standard dose [SD], low dose [LD] per label, LD inconsistent per label prescribing, and untreated) were evaluated based on OAC treatment. Duration of index OAC treatment, time to discontinuation and incidence rates across OAC treated cohorts were assessed. A machine learning method (Elastic Net) identified factors associated with being undertreated or untreated. Results: The final sample included 13,341 patients (mean age 78.5 and female 47%). Within a 180-day timeframe post-diagnosis, 76% of patients received OAC treatment, while 24% did not receive any OAC therapy. Among those treated with DOAC (n=9947), 74% were administered SD (n=7238), 18% received LD per labels (n=1756) and 10% were inappropriately prescribed LD of DOACs (n=953). Both LD cohorts tended to have shorter duration of OAC therapy (figure) and higher discontinuation rates (per 100 person-years; LD per label: 42.97; LD not per label: 39.11) compared to the SD cohort (SD: 31.67). Patients who were untreated were associated with elevated bleeding risk factors such as renal disease and prior bleeding history; patients who received inappropriate LD were associated with age above 75, renal disease, GI conditions with PPI (proton pump inhibitor) concomitant treatments when compared to SD cohort. Conclusions: In our study, a considerable proportion of AF patients remained untreated/undertreated and were associated with bleeding risk factors, highlighting the unmet needs within this population. Exploring potential alternative treatment options with enhanced safety profiles could offer substantial benefits to patients in need.

From the INVICTUS Trial to Current Considerations: It’s Not Time to Retire Vitamin K Inhibitors Yet!

Atrial fibrillation (AF) is a common arrhythmia in clinical practice, and oral anticoagulation is the cornerstone of stroke prevention in AF. Direct oral anticoagulants (DOAC) significantly reduce the incidence of intracerebral hemorrhage with preserved efficacy for preventing stroke compared to vitamin K antagonists (VKA). However, the pivotal randomized controlled trials (RCTs) of DOAC excluded patients with valvular heart disease, especially mitral stenosis, which remains an exclusion criterion for DOAC use. The INVICTUS study was a large multicenter global RCT aimed at evaluating the role of DOAC compared to VKA in stroke prevention among patients with rheumatic valvular AF. In this study, rivaroxaban failed to prove superiority over VKA in preventing the composite primary efficacy endpoints of stroke, systemic embolism, myocardial infarction, and death. Unfortunately, the bleeding rates were not lower with rivaroxaban either. The death and drug discontinuation rates were higher in the DOAC arm. Close to the heels of the dismal results of INVICTUS, an apixaban trial in prosthetic heart valves, PROACT-Xa, was also prematurely terminated due to futility. Hence, for AF complicating moderate-to-severe mitral stenosis or prosthetic valve VKA remains the standard of care. However, DOAC can be used in patients with surgical bioprosthetic valve implantation, TAVR, and other native valve diseases with AF, except for moderate-to-severe mitral stenosis. Factor XI inhibitors represent a breakthrough in anticoagulation as they aim to dissociate thrombosis from hemostasis, thereby indicating a potential to cut down bleeding further. Multiple agents (monoclonal antibodies—e.g., osocimab, anti-sense oligonucleotides—e.g., fesomersen, and small molecule inhibitors—e.g., milvexian) have garnered positive data from phase II studies, and many have entered the phase III studies in AF/Venous thromboembolism. Future studies on conventional DOAC and new-generation DOAC will shed further light on whether DOAC can dethrone VKA in valvular heart disease.

Temporal trends of prescription rates, dosing of non-vitamin K antagonist oral anticoagulants and clinical outcomes in patients with atrial fibrillation

Abstract Background The launch of non-vitamin K antagonist oral anticoagulant (NOAC) has revolutionized the landscape of stroke prevention in atrial fibrillation (AF). We aimed to analyze the temporal trends of prescription rates of oral anticoagulants (OACs), NOAC dosing, clinical outcomes and in patients with AF. Methods This was a retrospective study using the Taiwan National Health Insurance Research Database. During 2011 to 2020, A total of 249,107 patients aged ≥30 years with newly diagnosed AF were identified. We analyzed the 1-year risks of ischemic stroke, intracranial hemorrhage (ICH), and all-cause mortality for overall population and specifically for NOAC users. Results The prescription rate of OAC increased from 22.1% in year 2011 to 57.7% in 2020 (P<0.001) with NOAC accounting for 91.0% of overall OAC prescriptions. Compared to patients with incident AF diagnosed in 2011, there were increasing trends for a greater decrease in the risks of ischemic stroke (adjusted hazard ratios [aHRs] 0.914 in 2012, 0.879 in 2013, 0.925 in 2014, 0.822 in 2015, 0.754 in 2016, 0.763 in 2017, 0.769 in 2018, 0.713 in 2019 and 0.707 in 2020; all P<0.05) and mortality (aHRs 0.903 in 2014, 0.899 in 2015, 0.830 in 2016, 0.808 in 2017, 0.788 in 2018, 0.810 in 2019, 0.788 in 2020; all P<0.05), while the risk of ICH did not change significantly (Figure 1). For NOAC users, the percentages of high-dose NOACs increased from 11.04% in year 2012 to 44.29% in year 2019 to 2020. The increasing trend in the use of high-dose NOACs was temporally associated with a lower risk of ischemic stroke observed for patients receiving NOACs in year 2015 to 2017 (aHR 0.794) and year 2018 to 2020 (aHR 0.688) compared to those in year 2012 to 2014 (Figure 2). Conclusion In this nationwide cohort study, there was an increasing trend of OAC prescription, temporally associated with a decline of the risk of ischemic stroke and mortality. Even among NOACs users, the risk of ischemic stroke declined gradually, partly explained by the increasing prescriptions of high-dose NOACs.

Factor XI/XIa Inhibitors: What We Now Know

The emerging class of agents targeting factor XI/XIa offers the paradigm-shifting possibility of ‘haemostasis-sparing anticoagulation’: protection from stroke and other thromboembolic events with a benign bleeding profile. With three investigational agents now into late-phase development, two presentations delivered at the European Society of Cardiology (ESC) Congress 2024, held in London, UK, have added to our knowledge of this innovative and diverse class. The first of these presentations shared the full data from the OCEANIC-AF Phase III trial, in which the small molecule factor XIa inhibitor asundexian was compared with the factor Xa inhibitor apixaban for stroke prevention in atrial fibrillation, and reviewed the probable reasons for the failure of this trial to meet its efficacy endpoint. The second presentation was a secondary analysis from the AZALEA-TIMI 71 Phase II trial, in which the safety of the monoclonal antibody factor XI inhibitor abelacimab was compared with that of the factor Xa inhibitor rivaroxaban in patients with atrial fibrillation undergoing invasive procedures. This article is based on a post-ESC interview with Jeffrey I. Weitz, Professor of Medicine and Biochemistry and Biomedical Sciences at McMaster University, Canada; Canada Research Chair (Tier 1) in Thrombosis and the Heart and Stroke Foundation; J.F. Mustard Chair in Cardiovascular Research; Executive Director of the Thrombosis and Atherosclerosis Research Institute (TaARI), in Hamilton, Canada; and Secretary General of the International Society on Thrombosis and Haemostasis (ISTH). It assesses the current status and future prospects of the factor XI/XIa inhibitor class in light of these recent developments.

Trends over time in oral anticoagulation and stroke rates in atrial fibrillation: A community-based study

ObjectivesOver the last decade, direct oral anticoagulants (DOAC) have become preferred over warfarin for stroke prevention in atrial fibrillation (AF). The objectives of this study were to quantify the shift over time from warfarin to DOACs and parallel changes in ischemic and hemorrhagic stroke rates in AF. Materials and methodsThis community-based retrospective study was undertaken within a single integrated health care network from 2011 to 2021. Changes over time in warfarin and DOAC use were quantified by year, both overall and stratified by CHA2DS2-VASc score. Ischemic and hemorrhagic stroke rate changes over time were evaluated by Poisson regression. Stroke rates were evaluated in different time eras: 2011–2015 and 2016–2021. ResultsAmong 31,978 AF patients followed an average of 5.5 years, any OAC use increased from 50.2 % (2011) to 59.4 % (2020) (p < 0.001). Warfarin use decreased from 49.3 % to 30.8 %, while DOAC use increased from 2.0 % to 30.8 % (both p < 0.001). In 2020, patients with CHA2DS2-VASc 0–1 and 2–5 were more likely to use DOACs than warfarin (18.6 % vs. 6.7 %; 33.0 % vs. 28.2 %), whereas in CHA2DS2-VASc 6–9 DOACs were used less frequently (30.0 % vs. 40.8 %). Ischemic stroke rates significantly increased by 19 % (95 % CI: 7 %, 32 %) from 2011 to 2015, but significantly decreased by 18 % (10 %, 26 %) from 2016 to 2021. Hemorrhagic stroke rates stabilized in 2016–2021 (+3 %; −18 %, 30 %) after increasing in 2011–2015 (+36 %; 4 %, 78 %). ConclusionImprovements in ischemic and hemorrhagic stroke rates coincided temporally with increased uptake of OACs and a shift toward increased uptake of DOACs relative to warfarin.

Comparison of Oral Anticoagulants vs. Warfarin for Stroke Prevention in Atrial Fibrillation: A Meta-Analysis

Background: Atrial fibrillation (AF) significantly increases the risk of ischemic stroke, necessitating effective anticoagulation therapy. Warfarin has been the standard treatment, but direct oral anticoagulants (DOACs) have emerged as a safer and more effective alternative.Objective: To compare the efficacy and safety of DOACs versus warfarin in stroke prevention among AF patients.Methods: A comprehensive literature search was conducted in PubMed, EMBASE, Cochrane Library, Web of Science, and Scopus following PRISMA guidelines. Randomized controlled trials and observational studies comparing DOACs (dabigatran, rivaroxaban, apixaban, edoxaban) with warfarin in AF patients were included. Primary outcomes were ischemic stroke or systemic embolism, and secondary outcomes included all-cause mortality, major bleeding, intracranial hemorrhage (ICH), and gastrointestinal bleeding. Hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated using a random-effects model.Results: A total of 35 studies involving 172,350 patients were analyzed. DOACs significantly reduced ischemic stroke or systemic embolism (HR: 0.78, 95% CI: 0.72–0.84, p &lt; 0.001) and all-cause mortality (HR: 0.85, 95% CI: 0.79–0.92, p = 0.002). Major bleeding risk was lower (HR: 0.88, 95% CI: 0.80–0.96, p = 0.005), but gastrointestinal bleeding was higher (HR: 1.20, 95% CI: 1.10–1.30, p &lt; 0.001).Conclusion: DOACs provide superior efficacy and safety in stroke prevention compared to warfarin, despite a higher risk of gastrointestinal bleeding.

Assessing methods to ascertain persistence and adherence of oral anticoagulants in patients with atrial fibrillation

BackgroundPersistence and adherence to oral anticoagulants (OACs) is crucial for its effectiveness in stroke prevention in atrial fibrillation (AF). We aimed to assess the impact of different ascertainment methods on estimated persistence rates. MethodsWe conducted a retrospective cohort study based on the Medicare claims data (01/01/2013-12/31/2019). We built an incident user cohort of OAC (apixaban, dabigatran, edoxaban, rivaroxaban, and warfarin) prescription filling. We measured OAC medication persistence and adherence using the following approaches: 1) treatment-anniversary based persistence: if there is an active prescription overlapping the 180th and 365th day with vs. without a 15-day buffer period (i.e., overlapping with 165th-195th and 350th-380th day); 2) dispensing-gap-based persistence: if there is OAC discontinuation defined as having gap between prescriptions more than a threshold (e.g., 5 to 60 days) and secondarily, 3) proportion of days covered (PDC) adherence: proportion of days in which patient had filled medication available over the 365-day interval. ResultsWe identified 1,398,692 patients who initiated OACs during the study interval. With the treatment-anniversary based approach, only 51.2 to 65.4% of the patients persisted with the medication for either warfarin or DOACs at 180 days, and the number dropped to 43.4 to 60.7% at one year. Adding a 15-day buffer period increased the treatment-anniversary based persistence rates by 6.5 to 10.5%. When the allowable gap increased from 5 to 60 days, the persistence rates increased by 36.3 to 42.4% for all OACs. Apixaban users had the highest PDC (74 to 75%) over the 365 days, compared to other OACs (60 to 69%). ConclusionsWe found that the estimated persistence rates are sensitive to the choice of ascertainment methods. When reporting and comparing persistence findings using the claims database, definitions of OAC discontinuation must be clearly delineated.

Will Factor XI Inhibitors Replace Current Anticoagulants for Stroke Prevention in Atrial Fibrillation?

This review provides an overview of the factor XI (FXI) inhibitor hypothesis for the development of novel anticoagulants which may be safer to those currently used in clinical practice and describes preliminary clinical data from phase 2 dose-ranging studies of patients with atrial fibrillation. Recent data from phase 2 dose ranging studies demonstrate substantial reductions in bleeding with FXI pathway inhibition compared with currently approved anticoagulants. However, larger studies are necessary to demonstrate efficacy of FXI inhibition for stroke prevention in atrial fibrillation. FXI pathway inhibition holds great promise for revolutionizing the landscape of anticoagulation for atrial fibrillation, primarily by reducing bleeding risk; however, further data are necessary to demonstrate efficacy.

Impact of shared decision-making in Taiwanese patients with atrial fibrillation eligible for novel oral anticoagulant therapy

Background/PurposeShared decision-making (SDM) promotes patient awareness about medical conditions and treatments, facilitating patient involvement in care decisions. This two-stage multicenter study evaluated impacts of SDM in Taiwanese adults with atrial fibrillation (AF) eligible for novel oral anticoagulant (NOAC) therapy. MethodsParticipants were NOAC-naïve (part I) or dabigatran-experienced (part II). During Stage I, part I participants (n = 124) completed a semi-structured survey (understanding evaluation sections only) before and after viewing SDM materials on stroke prevention for AF. Surveys collected data on anxiety about AF, confidence in healthcare professionals, usefulness of the SDM materials, and perception of different NOACs. During Stage II, part I participants after being prescribed NOACs, and part II participants completed another survey to compare impacts of SDM. ResultsDuring Stage I, dabigatran was the preferred NOAC after viewing the SDM materials among 90% of part I participants. During Stage II, both part I (n = 87) and part II participants (n = 104) completed another survey. Fewer part I participants were anxious about AF (p < 0.01), and more had confidence in healthcare professionals (p < 0.01) after viewing SDM materials than before. Most part I participants (≥90%) rated the SDM materials as “very helpful”. In Stage II, participants viewing SDM before initiating dabigatran had lower anxiety (part I, 43%; part II, 53%; p < 0.01) and a higher trust (part I, 92%; part II, 84%; p < 0.01). ConclusionIn conclusion, SDM reduced anxiety and improved trust in healthcare professionals among NOAC-naïve participants with AF.

Milvexian vs apixaban for stroke prevention in atrial fibrillation: The LIBREXIA atrial fibrillation trial rationale and design

Direct oral anticoagulants are the standard of care for stroke prevention in eligible patients with atrial fibrillation and atrial flutter; however, bleeding remains a significant concern, limiting their use. Milvexian is an oral Factor XIa inhibitor that may offer similar anticoagulant efficacy with less bleeding risk. LIBREXIA AF (NCT05757869) is a global phase III, randomized, double-blind, parallel-group, event-driven trial to compare milvexian with apixaban in participants with atrial fibrillation or atrial flutter. Participants are randomly assigned to milvexian 100 mg or apixaban (5 mg or 2.5 mg per label indication) twice daily. The primary efficacy objective is to evaluate if milvexian is noninferior to apixaban for the prevention of stroke and systemic embolism. The principal safety objective is to evaluate if milvexian is superior to apixaban in reducing the endpoint of International Society of Thrombosis and Hemostasis (ISTH) major bleeding events and the composite endpoint of ISTH major and clinically relevant nonmajor (CRNM) bleeding events. In total, 15,500 participants from approximately 1,000 sites in over 30 countries are planned to be enrolled. They will be followed until both 430 primary efficacy outcome events and 530 principal safety events are observed, which is estimated to take approximately 4 years. The LIBREXIA AF study will determine the efficacy and safety of the oral Factor XIa inhibitor milvexian compared with apixaban in participants with either atrial fibrillation or atrial flutter. ClinicalTrials.gov NCT05757869.

Cost-Effectiveness of Rivaroxaban Compared with Other Direct Oral Anticoagulants for Stroke Prevention in Atrial Fibrillation in Public Sector of Malaysia

Despite the amount of research performed, the cost-effectiveness of direct oral anticoagulants (DOACs) in subpopulations with different risk factors for stroke has been very little studied. This study aims to explore the cost-effectiveness of the DOACs available in Malaysia in preventing stroke in different subpopulations from a government perspective. An existing Markov model was adapted to assess the cost-effectiveness of the DOACs that are available in Malaysia namely, apixaban (AP), dabigatran (DA) and rivaroxaban (RV). Each was compared with vitamin K antagonists (VKA) in stroke prevention in different patient subpopulations including chronic kidney disease (CKD), high-age, diabetes (DM), and prolonged hospital stay. Cost-effectiveness was assessed by the incremental cost-effectiveness ratio (ICER) benchmarked against the local threshold for cost-effectiveness. The total cost of VKA, AP, DA and RV was Malaysian Ringit (RM) RM9,811 (1USD=RM4.76), RM16,858, RM18,318 and RM20,161 respectively. The quality adjusted life-years (QALYs) gained compared with VKA were 6.11, 6.09 and 6.15 respectively. The ICER when compared with VKA at base case was 57,539, -90,682 and 68,156 respectively. AP had the most favourable ICER at base case. RV had the best ICER compared to AP and DA in patients with CKD and DM at a willingness-to-pay threshold of 1-GDP. Probabilistic sensitivity analysis showed that RV was consistently the most favourable DOAC under a threshold of 2-GDP for all subpopulations. These findings suggested that rivaroxaban has the most favourable ICER in the CKD and DM patient subgroups for stroke prevention among the DOACs available in Malaysia at a threshold of 2-GDP.

Risk of gastrointestinal bleeding in Asian patients receiving oral anticoagulants for stroke prevention in atrial fibrillation.

Non-vitamin K antagonist oral anticoagulants (NOACs) are increasingly used for stroke prevention in atrial fibrillation. At the Asia Pacific Advancing Patient care with EdoXaban 2023 meeting, experts shared insights on gastrointestinal bleeding with NOACs for stroke prevention in atrial fibrillation in Asian clinical practice, where NOACs have gained widespread acceptance due to their favourable profiles. Gastrointestinal bleeding risk varies amongst NOACs, emphasizing the importance of diligent patient assessment, dosage selection and vigilant monitoring. Edoxaban emerged as a viable option with a low gastrointestinal bleeding risk profile in Asian compared with non-Asian patients, supporting its continued clinical utilization for appropriate patients.

Comparison of oral anticoagulants for stroke prevention in atrial fibrillation using the UK clinical practice research Datalink Aurum: A reference trial (ARISTOTLE) emulation study.

Stroke prevention guidance for patients with atrial fibrillation (AF) uses evidence generated from randomised controlled trials (RCTs). However, applicability to patient groups excluded from trials remains unknown. Real-world patient data provide an opportunity to evaluate outcomes in a trial analogous population of direct oral anticoagulants (DOACs) users and in patients otherwise excluded from RCTs; however, there remains uncertainty on the validity of methods and suitability of the data. Successful reference trial emulation can support the generation of evidence around treatment effects in groups excluded or underrepresented in trials. We used linked United Kingdom primary care data to investigate whether we could emulate the pivotal ARISTOTLE trial (apixaban versus warfarin) and extend the analysis to investigate the impact of warfarin time in therapeutic range (TTR) on results. Patients with AF in the UK Clinical Practice Research Datalink (CPRD Aurum) prescribed apixaban or warfarin from 1 January 2013 to 31 July 2019 were selected. ARISTOTLE eligibility criteria were applied to this population and matched to the RCT apixaban arm on baseline characteristics creating a trial-analogous apixaban cohort; this was propensity-score matched to warfarin users in the CPRD Aurum. ARISTOTLE outcomes were assessed using Cox proportional hazards regression stratified by prior warfarin exposure status during 2.5 years of patient follow-up and results benchmarked against the trial results before treatment effectiveness was further evaluated based on (warfarin) TTR. The dataset comprised 8,734 apixaban users and propensity-score matched 8,734 warfarin users. Results [hazard ratio (95% confidence interval)] confirmed apixaban noninferiority for stroke or systemic embolism (SE) [CPRD 0.98 (0.82,1.19) versus trial 0.79 (0.66,0.95)] and death from any cause [CPRD 1.03 (0.93,1.14) versus trial 0.89 (0.80,0.998)] but did not indicate apixaban superiority. Absolute event rates for stroke/SE were similar for apixaban in CPRD Aurum and ARISTOTLE (1.27%/year), whereas a lower event rate was observed for warfarin (CPRD Aurum 1.29%/year, ARISTOTLE 1.60%/year). Analysis by TTR suggested similar effectiveness of apixaban compared with poorly controlled warfarin (TTR < 0.75) for stroke/SE [0.91 (0.73, 1.14)], all-cause death [0.94 (0.84, 1.06)], and superiority for major bleeding [0.74 (0.63, 0.86)]. However, when compared with well-controlled warfarin (TTR ≥ 0.75), apixaban was associated with an increased hazard for all-cause death [1.20 (1.04, 1.37)], and there was no significant benefit for major bleeding [1.08 (0.90, 1.30)]. The main limitation of the study's methodology are the risk of residual confounding, channelling bias and attrition bias in the warfarin arm, and selection bias and misclassification in the analysis by TTR. Analysis of noninterventional data generated results demonstrating noninferiority of apixaban versus warfarin consistent with prespecified benchmarking criteria. Unlike in ARISTOTLE, superiority of apixaban versus warfarin was not seen, possible due to the lower proportion of Asian patients and higher proportion of patients with well-controlled warfarin compared to ARISTOTLE. This methodological template can be used to investigate treatment effects of oral anticoagulants in patient groups excluded from or underrepresented in trials and provides a framework that can be adapted to investigate treatment effects for other conditions.

Left atrial appendage closure for stroke prevention in atrial fibrillation: current status and perspectives.

Atrial fibrillation (AF) is associated with an increased risk of stroke and systemic embolism, and the left atrial appendage (LAA) has been identified as a principal source of thromboembolism in these patients. While oral anticoagulation is the current standard of care, LAA closure (LAAC) emerges as an alternative or complementary treatment approach to reduce the risk of stroke or systemic embolism in patients with AF. Moderate-sized randomized clinical studies have provided data for the efficacy and safety of catheter-based LAAC, largely compared with vitamin K antagonists. LAA device iterations, advances in pre- and peri-procedural imaging, and implantation techniques continue to increase the efficacy and safety of LAAC. More data about efficacy and safety of LAAC have been collected, and several randomized clinical trials are currently underway to compare LAAC with best medical care (including non-vitamin K antagonist oral anticoagulants) in different clinical settings. Surgical LAAC in patients with AF undergoing cardiac surgery reduced the risk of stroke on background of anticoagulation therapy in the LAAOS III study. In this review, we describe the rapidly evolving field of LAAC and discuss recent clinical data, ongoing studies, open questions, and current limitations of LAAC.

Exploring the therapeutic utility of the factor XIa inhibitor asundexian.

In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time. Factor XIa inhibitors are a promising novel class of anticoagulants that attenuate pathological thrombosis with minimal interference with hemostasis. These effects contrast with those of conventional anticoagulants, which may exhibit adverse events of untoward bleeding precluding treatment in some patients. A variety of investigational pharmacological modalities have been developed and studied to target factor XIa. Asundexian is a small molecule inhibitor of factor XIa that has been evaluated in several clinical studies. It has been studied as an oral, once-daily medication and found to inhibit approximately 90% of factor XIa activity at doses of 20 to 50mg. Phase 2 trials have demonstrated the potential for improved safety compared to standard of care in certain treatment settings, such as in atrial fibrillation. For other indications, such as noncardioembolic stroke and acute myocardial infarction, asundexian has been used in addition to background antiplatelet therapy. In these instances, asundexian did not show a difference in the incidence of bleeding events compared to placebo. Phase 3 trials have recently been launched; however, the OCEANIC-AF trial was prematurely discontinued due to inefficacy of asundexian vs apixaban for stroke prevention in atrial fibrillation. Another phase 3 trial, OCEANIC-AFINA, is planned to compare asundexian to placebo in patients with atrial fibrillation at high risk for stroke who are deemed ineligible for anticoagulation.

Uncovering the Role of Direct Oral Anticoagulants in Stroke Prevention for Atrial Fibrillation: A Review of the Literature.

Atrial fibrillation (AF) is a predominant contributor to morbidity and mortality, and stroke prevention remains the mainstay for the management of AF. The precise mechanism involved in thrombus formation remains unknown. However, factors such as stretch-induced fibrosis, endothelial dysfunction, disordered atrial contractions, and pro-thrombotic states have been postulated for the development of AF. Various risk assessment strategies have been acknowledged for determining the risk of stroke in AF, of which the congestive heart failure, hypertension, age ≥75, diabetes, stroke, vascular disease, age between 65-74, and female sex (CHA2DS2-VASc) score remains the ultimate risk stratification tool. For the longest time, vitamin K antagonists (VKA) were the only oral anticoagulants available but were associated with an increased risk of bleeding. Recently, direct oral anticoagulants (DOACs) were approved and considered more efficient and safer than or as secure as warfarin in stroke prevention and lowering intra-cranial bleeding events. The pharmacodynamics and pharmacokinetics of DOACs were also clarified in this article. This review article compiles current evidence-based data on the role of DOACs, uncovering their underlying mechanisms, and comparing their efficacy with warfarin in stroke prevention in AF.

Novel Anticoagulants for Stroke Prevention in Atrial Fibrillation: A Comprehensive Review.

Atrial fibrillation (AF) is a prevalent cardiac arrhythmia associated with an increased risk of stroke due to disrupted heart function and potential clot formation. This review examines current management strategies for stroke prevention in AF, focusing on the efficacy, safety, and long-term outcomes of anticoagulation therapies. Anticoagulants, including novel oral anticoagulants (NOACs) and vitamin K antagonists, play a crucial role in reducing stroke risk by preventing clot formation in the heart. Recent studies highlight NOACs as superior alternatives to traditional therapies, offering improved safety profiles and enhanced patient adherence. Despite the risk of bleeding complications, judicious use of anticoagulants significantly improves clinical outcomes in AF patients. The review synthesizes evidence from clinical trials and meta-analyses to underscore the pivotal role of NOACs in transforming stroke prevention strategies in AF. Moreover, it discusses emerging interventions such as left atrial appendage occlusion and emphasizes the importance of personalized, patient-centered care in optimizing treatment decisions for AF patients at risk of stroke.

Use of digital patient decision-support tools for atrial fibrillation treatments: a systematic review and meta-analysis

ObjectivesTo assess the effects of digital patient decision-support tools for atrial fibrillation (AF) treatment decisions in adults with AF.Study designSystematic review and meta-analysis.Eligibility criteriaEligible randomised controlled trials (RCTs) evaluated digital...

Direct oral anticoagulants versus vitamin K antagonists as stroke prevention in atrial fibrillation after cardiac surgery: a systematic review and meta-analysis

Abstract Background Cardiothoracic surgery guidelines advocate the use of vitamin K antagonists (VKAs) in patients with atrial fibrillation (AF) in the first days to months after major cardiac surgery. No recommendations on choice of anticoagulant in the first months after cardiac surgery have been issued since 2008, before the use of direct oral anticoagulants (DOACs). The basis for this is a lack of data on the safety and efficacy of DOACs after cardiac surgery. Purpose To systematically assess and meta-analyze the existing evidence on the effect of DOACs compared with VKAs on efficacy and safety after cardic surgery. We hypothesized that DOACs are non-inferior to VKAs in the setting of AF after cardiac surgery. Methods We searched Ovid MEDLINE, Ovid EMBASE, the Cochrane Central Register of Controlled trials and Clinicaltrials.gov from inception till 20 June 2023 and screened references in relevant reviews as grey literature search. Observational studies and randomized controlled trials comparing DOACs with VKAs for stroke prevention in patients with (postoperative) atrial fibrillation after cardiac surgery were included, focusing on procedures through thoracoscopy or thoracotomy. Outcomes of interest included thromboembolic events, all-cause stroke, major bleeding and mortality up to 6 months after cardiac surgery and admission duration. A random effects model was used to determine pooled treatment effects. The level of evidence was rated following the GRADE recommendations. Results We identified 4,146 records of which ten were included, together reporting on &amp;gt; 30,000 patients. There were no significant differences in thromboembolic events (OR 0.98; 95% CI 0.61-1.58; I^2 0%; GRADE: very low), all-cause stroke (OR 1.14; 95% CI 0.51-2.54; I^2 0%; GRADE: very low), major bleeding (OR 0.91; 95% CI 0.51-1.62; I^2 53%; GRADE: very low), all-cause mortality (OR 1.00; 95% CI 0.73-1.37; I^2 0%; GRADE: low), admission duration (MD -0.33; 95% CI -1.16 – 0.49; I^2 0%; GRADE: very low) between DOACs and VKAs in the first 6 months after cardiac surgery. Conclusion Efficacy and safety of DOACs as stroke prevention in AF following cardiac surgery were similar to that of VKAs in ten studies comprising more than 30,000 patients. Based on the existing literature, there is insufficient evidence to recommend one class of oral anticoagulants over another in the first months after cardiac surgery.Forest plot of primary outcomes