Stroke Prevention In Atrial Fibrillation Research Articles

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 < 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 < 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

Percutaneous left atrial appendage closure for stroke prevention in hypertrophic cardiomyopathy patients with atrial fibrillation

BackgroundPercutaneous left atrial appendage closure (LAAC) is an effective alternative strategy for stroke prevention in patients with atrial fibrillation (AF) at high risk for bleeding with anticoagulation (AC). Efficacy of this strategy in hypertrophic cardiomyopathy (HCM) remains uncertain. ObjectiveThe study aimed to compare risk of stroke in HCM-AF patients treated with LAAC with those treated with AC. MethodsBy use of the TriNetX Global Research Network, HCM-AF patients from 2015 to 2024 were assigned to categories of treatment with LAAC and treatment solely with AC and observed for 3 years for ischemic stroke, systemic embolism, and all-cause mortality. Propensity score matching was used to limit confounders. ResultsOf 14,867 HCM-AF patients identified, 364 (2.5%) were treated with LAAC vs 14,503 (97.5%) treated with AC. HCM LAAC patients were older (72 vs 67 years; P < .001) and had more comorbidities and more prior bleeding events, including higher rate of prior gastrointestinal bleeding (68% vs 18%; P < .001), compared with HCM patients treated solely with AC. After propensity score matching, there was no baseline difference between groups including prior bleeding events (P > .05). During follow-up, HCM patients treated with LAAC had higher rates of ischemic stroke (13% vs 8%; hazard ratio, 1.9; P = .006) and systemic embolism (14% vs 9%; hazard ratio, 1.8; P = .006) but no difference in mortality compared with matched HCM patients receiving AC. ConclusionThese real-world data do not support percutaneous LAAC in HCM-AF patients as the primary treatment strategy during long-term AC to reduce stroke risk. However, LAAC may remain a reasonable option for HCM-AF patients who are unable to tolerate AC because of prohibitive bleeding risk.

Acute haemodynamic changes during left atrial appendage closure

Abstract Purpose Left atrial appendage closure (LAAC) presents an alternative treatment for stroke prevention in atrial fibrillation (AF) in patients with contraindication for long-term anticoagulation. However, even in patients in AF, left atrial appendage plays an important role in reservoir function of left atrium. The purpose of this study was to assess acute hemodynamic effects during LAAC. Methods Consecutive patients indicated for LAAC from January 2022 to October 2023 were enrolled. The invasive hemodynamic measurements were done at the beginning of the procedure after transseptal puncture, and at the end from the procedure after device deployment. Following parameters were measured: systolic, and diastolic blood pressure, and pressure in left atrium (LA), all measurements were done at rest and after 3 minute isometric exercise (handgrip). Results Thirty-two patients were included (age 76,2+7,1 yrs, 22 (69%) males, 23 (72%) permanent AF, left ventricular ejection fraction 52+11,8%). No patients experienced moderate/severe mitral insufficiency, the saline intake during procedure was 738 ml. Isometric exercise significantly increased the LA pressure: the LA pressures (rest/exercise) were 13.7+6.7 mmHg/16.7+8.8 mmHg (p=0.003) at the beginning of the procedure, and 17.0+7.3mmHg/20.0+7.3 mmHg (p=0.005) after device deployment. The LA pressure obtained after device deployment (both rest/exercise) were significantly higher compared to values obtained at the beginning of the procedure. (p=0.003). Conclusions LAAC is associated acute increase of both rest and exercise LA pressure. Whether its acute negative effect remains over time needs further investigation.

One-year effectiveness and safety outcomes of edoxaban treatment in Chinese patients with atrial fibrillation: First snapshot of more than 4,800 patients from the ETNA-AF-China study

Abstract Background Direct oral anticoagulants (DOACs) have become the first-line therapy for ischaemic stroke prevention in atrial fibrillation (AF) patients. Data on the effectiveness and safety of single DOAC in large Chinese populations are scarce. Purpose We firstly present the one-year outcome data of edoxaban treatment in 5001 Chinese AF patients. Methods This is a multi-centre, prospective, observational study, ETNA-AF-China, conducted in 89 centres from four economic regions in Mainland of China with a follow-up of two years. Primary endpoint of safety [bleeding events including intracranial hemorrhage (ICH), all-cause and cardiovascular (CV) mortality] and efficacy endpoints [stroke, systemic embolic events (SEE), transient ischemic attack (TIA)] were adjudicated. Annualised event rates and Kaplan­Meier (KM) survival curves are given. Results A total of 4822 patients (57.1% male) using edoxaban (60 mg OD: n=2614, 30 mg OD: n=2208) who completed one-year follow-up were included in the full analysis set. The mean (SD) age of the overall patient population was 70.3 (9.5) years, CHA2DS2-VASc and HAS-BLED scores were 2.9 (1.4), 1.7 (1.0), with creatinine clearance (CrCl) of 71.2 (27.7) mL/min. Patients receiving 30 mg OD edoxaban at baseline were older (73.4 vs 67.7 years), with higher CHA2DS2-VASc score (3.3 vs 2.6), larger percentage of frail (9.9% vs 3.4%), and higher renal impairment (defined as CrCl ≤80 mL/min, 70.3% vs 42.9%). Annualised rates for all-cause and cardiovascular death in the overall population were very low with 2.22%/year and 0.41%/year, respectively. (Figure 1) The death rates were nearly three times lower in those receiving standard dose (60 mg) than reduction dose (30 mg) of edoxaban. Annualised event rates for all stroke/SEE (1.03%/year) and ischemic stroke (0.60%/year) were similar between two dose groups. Overall, annualised rates for major bleeding (1.03%/year), ICH (0.18%/year), major gastrointestinal (GI) bleeding (0.48%/year) events were relatively low, and those on 60 mg dose experienced less above bleeding events. Cumulative survival analysis demonstrated a slow increase in time-to-first event curve of all-cause death; and from baseline to 1-year follow-up, significant lower events of all-cause death (log-rank p&amp;lt;0.001), major bleeding (p=0.002) in 60 mg vs 30 mg edoxaban groups. (Figure 2). Conclusion Low incidences of major bleeding, notably ICH, major GI bleeding, and CV death were observed in unselected 4822 patients with AF during 1-year of edoxaban treatment. These findings confirm the effectiveness and safety of routine edoxaban use in China, consistent with other countries, and reinforce the results of the ENGAGE AF-TIMI 48 trial.Figure 1Figure 2

Assessment of Days Alive Out of Hospital as a Possible End Point in Trials of Stroke Prevention for Atrial Fibrillation: A ROCKET AF Analysis.

Days alive out of hospital (DAOH) is an objective and patient-centered net benefit end point. There are no assessments of DAOH in clinical trials of interventions for atrial fibrillation (AF), and it is not known whether this end point is of clinical utility in these populations. 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) was an international double-blind, double-dummy randomized clinical trial that compared rivaroxaban with warfarin in patients with atrial fibrillation at increased risk for stroke. We assessed DAOH using investigator-reported event data for up to 12 months after randomization in ROCKET AF. We assessed DAOH overall, by treatment group, and by subgroup, including age, sex, and comorbidities, using Poisson regression. The mean±SD number of days dead was 7.3±41.2, days hospitalized was 1.2±7.2, and mean DAOH was 350.7±56.2, with notable left skew. Patients with comorbidities had fewer DAOH overall. There were no differences in DAOH by treatment arm, with mean DAOH of 350.6±56.5 for those randomized to rivaroxaban and 350.7±55.8 for those randomized to warfarin (P=0.86). A sensitivity analysis found no difference in DAOH not disabled with rivaroxaban versus warfarin (DAOH not disabled, 349.2±59.5 days and 349.1 days±59.3 days, respectively, P=0.88). DAOH did not identify a treatment difference between patients randomized to rivaroxaban versus warfarin. This may be driven in part by the low overall event rates in atrial fibrillation anticoagulation trials, which leads to substantial left skew in measures of DAOH.

Stroke prevention in atrial fibrillation : The ARTESIA study in the light of current knowledge

Stroke prevention in atrial fibrillation : The ARTESIA study in the light of current knowledge

Dual Antithrombotic Therapy versus Anticoagulant Monotherapy for Major Adverse Limb Events in Patients with Concomitant Lower Extremity Arterial Disease and Atrial Fibrillation: A Propensity Score Weighted Analysis

Patients with symptomatic lower extremity arterial disease (LEAD) are recommended to receive antiplatelet therapy, while direct oral anticoagulants (DOACs) are standard for stroke prevention in patients with atrial fibrillation (AF). For patients with concomitant LEAD and AF, data comparing dual antithrombotic therapy (an antiplatelet agent used in conjunction with a DOAC) vs. DOAC monotherapy are scarce. This retrospective cohort study, based on data from the Taiwan National Health Insurance Research Database, aimed to compare the efficacy and safety of these antithrombotic strategies. Patients with AF who underwent revascularisation for LEAD between 2012 - 2020 and received any DOAC within 30 days of discharge were included. Patients were grouped by antiplatelet agent exposure into the dual antithrombotic therapy and DOAC monotherapy groups. Inverse probability of treatment weighting was used to mitigate selection bias. Major adverse limb events (MALEs), ischaemic stroke or systemic embolism, and bleeding outcomes were compared. Patients were followed until the occurrence of any study outcome, death, or up to two years. A total of 1 470 patients were identified, with 736 in the dual antithrombotic therapy group and 734 in the DOAC monotherapy group. Among them, 1 346 patients received endovascular therapy as the index revascularisation procedure and 124 underwent bypass surgery. At two years, dual antithrombotic therapy was associated with a higher risk of MALEs than DOAC monotherapy (subdistribution hazard ratio [SHR] 1.34, 95% confidence interval [CI] 1.15 - 1.56), primarily driven by increased repeat revascularisation. Dual antithrombotic therapy was also associated with a higher risk of major bleeding (SHR 1.43, 95% CI 1.05 - 1.94) and gastrointestinal bleeding (SHR 2.17, 95% CI 1.42 - 3.33) than DOAC monotherapy. In patients with concomitant LEAD and AF who underwent peripheral revascularisation, DOAC monotherapy was associated with a lower risk of MALEs and bleeding events than dual antithrombotic therapy.