Non-central Nervous System Embolism Research Articles

Rate control or rhythm control in patients with atrial fibrillation and acute coronary syndrome or percutaneous coronary intervention

BackgroundRestoring and maintaining sinus rhythm in patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI) has been studied in clinical trials to reduce symptoms and improve quality of life. Limited data exist on the effectiveness of rate or rhythm control therapy in these patients. MethodsConsecutive patients with AF and ACS or referred for PCI were prospectively recruited in Fuwai Hospital during 2017–2020. The primary endpoints were all-cause death and major adverse cardiovascular and cerebrovascular events (MACCEs), including cardiovascular mortality, myocardial infarction, ischemic stroke, non-central nervous system embolism and ischemia-driven revascularization. Kaplan–Meier curves and Cox regressions were performed to evaluate the association between rhythm/rate control and subsequent outcomes. For the primary endpoints, we used the Benjamini–Hochberg correction for multiple comparisons. ResultsA total of 1499 patients with AF and ACS or undergoing PCI were included, with a median follow-up of 34.7 months. Compared to non-rate control, rate control strategy reduced the risk of subsequent MACCEs (adjusted HR, 0.320; 95 % CI 0.220–0.466; p <0.001; *p <0.002) and all-cause death (adjusted HR, 0.148; 95 % CI 0.093–0.236; p <0.001; *p <0.002). Similar trends were observed across all predefined subgroups (p <0.001). In the final multivariate model, rhythm control was not associated with a lower subsequent MACCEs but significantly improved all-cause mortality compared to non-rhythm control (adjusted HR, 0.546; 95 % CI 0.313–0.951; p =0.033; *p =0.044). ConclusionsIn this real-world study, rate control strategy was associated with lower risk of MACCEs and all-cause death in AF and ACS or undergoing PCI. Besides, management with rhythm control strategy may improve all-cause mortality.

Baseline characteristics and risk of major bleeding in Taiwanese patients with atrial fibrillation and renal impairment receiving rivaroxaban: the prospective XARETO registry

Abstract Background Data about the use of direct oral anticoagulants (DOACs) in the prospective registry of Asian atrial fibrillation (AF) patients with renal dysfunction, especially those with a creatinine clearance (CCr) between 15 to 30 ml/min, are limited. This study aimed to investigate the safety of rivaroxaban in Taiwanese AF patients with renal impairment in the daily practice. Methods XARETO (Xarelto for the prevention of stroke and non-central nervous systemic embolism in non-valvular atrial fibrillation with REnal impairment in Taiwanese pOpulation) is a multi-center, non-interventional, single arm prospective observational cohort study performed in Taiwan. Subjects with non-valvular AF aged &amp;gt;=20 years with a documented CCr of 15-50 ml/min within 6 months before the enrollment were enrolled. All subjects were prescribed rivaroxaban for stroke prevention. The major bleeding was defined as a bleeding events with fall in Hgb of &amp;gt;=2 g/dL or a transfusion of &amp;gt;= 2 units of packed red blood cells or whole blood or occurrence of bleeding at a critical site or mortality. Results A total of 493 patients were enrolled. The mean age was 78.3 years old and 59.6% was male. The mean CHA2DS2-VASc and HAS-BLED scores were 4.4 and 2.9, respectively. Co-morbidities were as follows: 41.0% patients had chronic heart failure, 83.2% had hypertension, 40.8% had diabetes and 14.8% had prior stroke/transient ischemic attack/systemic embolic events. The mean CCr was 35.19 ml/min, and 159 (32.3%) of them has a CCr between 15-29 ml/min. During the follow up, there were 23 patients with 26 adjudicated major bleeding events with the incidence rate of 6.2 per 100 person-years (95% CI 3.9-9.3). Of these patients, there were 15 patients with 16 adjudicated major bleeding events considered as related to the rivaroxaban treatment with the incidence rate of 4.0 per 100 person-years (95% CI 2.2-6.6)(Figure) Conclusions In high-risk Taiwan AF patients (mean CHA2DS2-VASc score 4.4) with renal impairment (mean CCr 35.19 ml/min, 32.3% between 15-29 ml/min), the safety of rivaroxaban was confirmed in the prospective XARETO study.

Left atrial strain and risk of systemic embolic event in rheumatic mitral stenosis with sinus rhythm

Abstract Backgrounds Stroke and systemic embolism might be an important complication of rheumatic mitral stenosis (MS) even though patients are in sinus rhythm (SR), but the risk of embolic events in this population are not well studied. Purpose We aimed to evaluate the risk factors of embolic events in patients with rheumatic MS and SR. Methods From the multi-center retrospective registry of 2426 patients with rheumatic MS, we included patients with rheumatic MS and SR (n=583) between January 2000 and December 2021. After exclusion of patients who had history of systemic embolic events, taking the anticoagulants, combined significant aortic valve dysfunction, and a history of valve surgery. We finally analyzed 443 patients. The primary outcome was defined as composite of stroke, transient ischemic attack, noncentral nervous system embolism. Results Among 448 patients (77.1% female; mean age, 52.3 ± 10.1 years), systemic embolic events developed in 38 (8.4 %) patients with annual incidence rate of 4.6/100 person-year during mean follow-up period of 96.4 ± 61.1 months (median 94.2 months). Patients who had systemic embolic events were significantly older and had higher the prevalence of hypertension and diabetes than those who did not, without significant differences in left atrial (LA) dimensions, volumes, pulmonary artery systolic pressure. Instead, LA strain was significantly impaired in patients with systemic embolic events (19.1 ± 9.3 vs. 15.5 ± 8.07, p= 0.034). In the multivariate analysis, LA strain was independent predictors of systemic embolic events [HR 0.96, 95 % CI: 0.93-0.99; P = 0.021], after adjustment for confounding factors. The impaired LA strain (LA reservoir strain &amp;lt; 16.6 %) also had incremental prognostic value for development of systemic embolic events over clinical factors and traditional echocardiographic parameters (Figure). Conclusions Impaired LA strain is a predictor of stroke and systemic embolism in patients with rheumatic MS in SR. Considering the risk for embolism, oral anticoagulation might be considered in patients with rheumatic MS in SR and impaired LA strain.Figure

XaMINA: A Real-World, Prospective, Observational Study of Treatment-Naïve Patients Treated with Rivaroxaban for Stroke Prevention in Atrial Fibrillation in Asia.

The efficacy and safety of rivaroxaban for the prevention of stroke and systemic embolism have been demonstrated in Asian and non-Asian patients with non-valvular atrial fibrillation (NVAF) in multiple studies. However, limited published data exist on its use specifically in treatment-naïve patients from the Asia region. Patients in South Korea and Taiwan can now receive rivaroxaban as first-line therapy, allowing for data generation in this patient group. XaMINA was a prospective, real-world, multicenter, single-arm, observational cohort study of patients with NVAF in South Korea and Taiwan naïve to anticoagulation and initiating rivaroxaban. The primary outcome was major bleeding; secondary outcomes included all-cause mortality, symptomatic thromboembolic events, and treatment persistence. In total, 1094 patients were included and the follow-up was 1year. The baseline mean CHADS2 score was 1.63±0.98, mean CHA2DS2-VASc score was 2.92±1.42, and mean HAS-BLED score was 1.00±0.75. The primary outcome occurred in 20 (1.8%) patients [incidence rate 2.1 events per 100 patient-years (95% CI 1.35-3.25)]. Thromboembolic events occurred in 9 (0.8%) patients, of whom 5 (0.5%) had stroke, 3 (0.3%) myocardial infarction, and 1 (0.1%) a transient ischemic attack. There were no cases of non-central nervous system systemic embolism, and 735 (67.2%) patients persisted with rivaroxaban treatment for 1year. XaMINA demonstrated low incidence rates of major bleeding events and thromboembolic events in patients with NVAF newly initiating rivaroxaban in South Korea and Taiwan, consistent with previous real-world studies reconfirming the results of the ROCKET AF study. The trial was registered on ClinicalTrials.gov (identifier NCT03284762) on 15 September 2017.

Validation of the Academic Research Consortium for High Bleeding Risk criteria in Chinese patients with atrial fibrillation and acute coronary syndrome or undergoing percutaneous coronary intervention

BackgroundThis study aims to validate the Academic Research Consortium for High Bleeding Risk (ARC-HBR) criteria in Chinese patients with atrial fibrillation (AF) and acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI) who received both oral anticoagulants (OAC) and antiplatelet therapy (APT). Methods930 consecutive patients with AF and ACS or undergoing PCI receiving both OAC and APT were recruited and followed up for 1 year. The primary endpoint was BARC type 3 or 5 bleeding. The secondary endpoints included BARC type 2, 3, or 5 bleeding, TIMI major bleeding, TIMI major or minor bleeding, and major adverse cardiovascular events (a composite of all-cause death, stroke, non-central nervous system embolism, myocardial infarction, definite or probable stent thrombosis, and target vessel revascularization). Cox regressions were performed to evaluate the association between the ARC-HBR score and outcomes. Discrimination was evaluated through analysis of the receiver operating characteristic (ROC) curves, net reclassification improvement (NRI), and integrated discrimination improvement (IDI). ResultsCompared to patients with no HBR other than OAC, patients with HBR besides OAC tended to have more comorbidities and worse outcomes. The ARC-HBR score was significantly associated with the primary and secondary endpoints, both as a continuous variable and as a categorical variable. The ARC-HBR score performed better than the HAS-BLED score (c-statistic: 0.692 vs. 0.575, NRI = 0.313, IDI = 0.061) and the PRECISE-DAPT score (c-statistic: 0.692 vs. 0.616, NRI = 0.393, IDI = 0.049). ConclusionsIn patients with AF and ACS or undergoing PCI receiving both OAC and APT, the ARC-HBR score was a significant predictor of 1-year bleeding and ischemic endpoints. The ARC-HBR score performed better than the HAS-BLED score and the PRECISE-DAPT score in BARC type 3 or 5 bleeding prediction.

Real-world safety and effectiveness of rivaroxaban using Japan-specific dosage during long-term follow-up in patients with atrial fibrillation: XAPASS.

The Xarelto Post-Authorization Safety and Effectiveness Study in Japanese Patients with Atrial Fibrillation (XAPASS) was designed to investigate safety and effectiveness during long-term follow-up of rivaroxaban treatment, using reduced doses compared with other global regions, in Japanese patients with non-valvular atrial fibrillation in real-world clinical practice. In this prospective, open-label, single-arm, observational study, 11,308 patients with non-valvular atrial fibrillation newly prescribed rivaroxaban (15/10 mg once daily) at 1416 sites across Japan were enrolled and followed for a mean of 2.5 years. In total, 10,664 and 10,628 patients were included in the safety and effectiveness analyses, respectively. In the safety population, mean (standard deviation) age was 73.1 (9.8) years and Congestive heart failure, Hypertension, Age ≥75 years, Diabetes mellitus, previous Stroke/TIA (2 points) (CHADS2) score was 2.2 (1.3). Incidences (95% confidence intervals) of any and major bleeding were 3.77 (3.53-4.01) and 1.16 (1.03-1.29) events per 100 patient-years, respectively. Age ≥75 years, creatinine clearance <50 mL/min, diabetes mellitus, and vascular disease were independently associated with incidence of major bleeding. The primary composite effectiveness outcome of stroke, non-central nervous system systemic embolism, and myocardial infarction occurred at an incidence (95% confidence interval) of 1.32 (1.18-1.46) events per 100 patient-years. Age ≥75 years, hypertension, prior ischemic stroke/transient ischemic attack, and concomitant use of antiplatelets were independently associated with incidence of the composite outcome of stroke, non-central nervous system systemic embolism, and myocardial infarction. In the XAPASS, a large-scale study involving a broad range of patients with non-valvular atrial fibrillation newly prescribed rivaroxaban using Japan-specific dosage in real-world clinical practice, no unexpected safety or effectiveness concerns were detected during up to 5 years of follow-up.

Long-term outcomes of Japan-specific dosage of rivaroxaban in high-risk patients with non-valvular atrial fibrillation: analysis from the XAPASS

Abstract Background XAPASS is a real-world, prospective, single-arm, observational study conducted as a post-marketing surveillance mandated by the health authority in Japan. Nowadays, direct oral anticoagulant therapy using factor Xa or thrombin inhibitor has been the standard of care for patients with non-valvular atrial fibrillation (NVAF) to prevent ischemic stroke. However, the clinical impact of reduced dosage (approved dose of 15 or 10 mg once daily in Japan is relatively reduced compared to global dosage) factor Xa inhibitor rivaroxaban in high-risk patients remains unclear. Purpose The present sub-analysis of XAPASS was carried out to assess long-term safety and effectiveness of reduced-dose rivaroxaban in high-risk NVAF patients for bleeding and thromboembolism. Methods All patients with NVAF who were newly started on rivaroxaban were eligible for surveillance. The principal safety outcome was a composite of major and non-major bleeding events, and the primary effectiveness outcome was a composite of ischaemic stroke, haemorrhagic stroke, non-central nervous system systemic embolism (non-CNS SE), and myocardial infarction (MI). In this present sub-analysis, high-risk patients were defined as those who had two of the following three risk factors: elderly (≥75 years old), low body weight (≤50 kg), and renal impairment (CrCl &amp;lt;50 mL/min). Results In total, 11,308 patients were enrolled between April 2012 and June 2014 from 1,419 hospitals, and overall data were analysed from 10,664 patients from whom data were collected. Among them, 3,694 patients matched the criteria for the high-risk patients defined in this sub-analysis, and 6,970 patients did not match the criteria (non-high-risk patients). The mean treatment duration was 791±673 days in the high-risk patients and 944±709 days in the non-high-risk patients. Mean patient age was 80.9±5.5 years and 69.0±9.0 years at baseline, respectively. Mean CHADS2 score was 2.8 and 1.8, and CHA2DS2-VASc score was 4.4 and 2.9, respectively. The rates of CHADS2 component comorbidities were lower in the non-high-risk patients except for diabetes mellitus. The incidence rates of any bleeding, major bleeding, and the primary effectiveness outcomes were 4.8, 1.6, and 2.1%/patient-year in the high-risk patients. The incidence rates of these clinical events in the non-high-risk patients were 3.3, 0.9, and 1.0%/patient-year, respectively. Conclusions Incidence rates of long-term bleeding and thromboembolism were higher in the high-risk patients than in the non-high-risk patients. However, the rates of these outcomes using the Japan-specific reduced dose were not so high. Furthermore, the balance between safety and effectiveness outcomes was within an acceptable range. The present study provides useful information for physicians to stratify high-risk patients using the reduced dose in daily clinical practice. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Bayer Yakuhin Ltd.

A prospective, observational study of rivaroxaban for stroke prevention in atrial fibrillation: the XANAP Korea.

Background/AimsAtrial fibrillation (AF)-related stroke accounts for 20% of ischemic strokes. Rivaroxaban use in AF patients for preventing stroke and systemic embolism was approved in 2013 in Korea. This study was to investigate the safety and effectiveness of rivaroxaban use in Korean patients with non-valvular AF in a real-world setting.MethodsThis was an analysis of the Korean patients in Xarelto for Prevention of Stroke in Patients with Atrial Fibrillation in Asia-Pacific (XANAP), which was a prospective, observational cohort study including patients with non-valvular AF starting rivaroxaban treatment to prevent stroke or non-central nervous system systemic embolism (non-CNS SE), conducted in 10 Asian countries.ResultsA total of 844 patients were enrolled in the Korean portion of the XANAP study. In XANAP Korea, the mean age was 70.1 years and 62.6% were males. The mean CHADS2 score was 2.5 and the mean CHA2DS2-VASc score was 3.8. 47% of the patients had experienced prior stroke or non-CNS SE or transient ischemic attack. 73.6% of the patients had CHADS2 score ≥ 2. Incidence proportions of 0.8% of the patients (1.1 per 100 patient-years) developed adjudicated treatment-emergent major bleeding. Death was observed in 1.2% of the patients. The incidence of non-major bleeding as well as thromboembolic event were 8.4% (11.6 per 100 patient-years) and 1.5% (2.0 per 100 patient-years), respectively.ConclusionsThis study reaffirmed the consistent safety profile of rivaroxaban. We found consistent results with overall XANAP population for rivaroxaban in terms of safety in non-valvular AF patients for the prevention of stroke and non-CNS SE.

Factor Xa inhibitors in patients with continuous-flow left ventricular assist devices.

Warfarin is standard anticoagulation therapy for patients with a continuous-flow left ventricular assist device (CF-LVAD). However, warfarin requires regular monitoring and dosage adjustments and fails for many patients, causing thromboembolic and bleeding events. Factor Xa inhibitors have been shown to be noninferior to warfarin in preventing strokes and are associated with less intracranial hemorrhage in patients with atrial fibrillation. We evaluated treatment safety and effectiveness in CF-LVAD patients who switched from warfarin to a factor Xa inhibitor (apixaban or rivaroxaban) after warfarin failure. This was a retrospective, single-center study of patients treated between 2008 and 2018. We assessed the occurrence of stroke, non-central nervous system (CNS) embolism, pump thrombosis, and major gastrointestinal bleeding and intracranial hemorrhage during therapy. We identified seven patients: five were male, the average body mass index was 30kg/m2, and average age was 56years. Preimplantation comorbidities included hypertension (all patients) and diabetes mellitus, ischemic cardiomyopathy, atrial fibrillation, and previous myocardial infarction (fourpatients each). Overall, patients received warfarin for 3968days and apixaban/rivaroxaban for 1459days. The warfarin group was within the therapeutic INR range (2.0-3.0) 30% of the time. Complication rates did not differ between warfarin and apixaban/rivaroxaban: strokes, 0.20 vs none, non-CNS embolism, 0.54 vs none; pump thrombosis, 0.27 vs none; major gastrointestinal bleeding, 0.20 vs 0.50; intracranial hemorrhage, 0.13 vs none. Factor Xa inhibitors may be viable treatment options for CF-LVAD patients for whom warfarin therapy has failed. Large prospective studies are necessary to confirm these results.

Association of frailty and cognitive impairment with benefits of oral anticoagulation in patients with atrial fibrillation

The incidence of cognitive impairment and frailty increase with age and may impact both therapy and outcomes in atrial fibrillation (AF). We examined the prevalence of clinically recognized cognitive impairment and frailty (as defined by the American Geriatric Society Criteria) in the Outcomes Registry for Better Informed Care in AF (ORBIT AF) and associated adjusted outcomes via multivariable Cox regression. The interaction between cognitive impairment and frailty and oral anticoagulation (OAC) in determining outcomes was examined. Among 9749 patients with AF [median (IQR) age 75 (67-82) y, 57% male], cognitive impairment and frailty was identified in 293 (3.0%) and 575 (5.9%) patients respectively. Frail patients (68 vs 77%, P < .001) and those with cognitive impairment (70 vs 77%, P = .006) were both less likely to receive an OAC. Both cognitive impairment [HR (95% CI) 1.34 (1.05-1.72), P = .0198] and frailty [HR 1.29 (1.08-1.55), P = .0060] were associated with increased risk of death. Cognitive impairment and frailty were not associated with stroke/transient ischemic attack (TIA) or major bleeding. In multivariable analysis, there was no interaction between OAC use and cognitive impairment or frailty in their associations with mortality, major bleeding and a composite end point of stroke, non-central nervous system systemic embolism, TIA, myocardial infarction or cardiovascular death. Those with cognitive impairment or frailty in AF had higher predicted risk for stroke and higher observed mortality, yet were less likely to be treated with OAC. Despite this, the benefits of OAC were similar in patients with and without cognitive impairment or frailty.

XANTUS-EL: A real-world, prospective, observational study of patients treated with rivaroxaban for stroke prevention in atrial fibrillation in Eastern Europe, Middle East, Africa and Latin America.

BackgroundThe prospective, observational XANTUS study demonstrated low rates of stroke and major bleeding in real-world rivaroxaban-treated patients with non-valvular atrial fibrillation (NVAF) from Western Europe, Canada and Israel. XANTUS-EL is a component of the overall XANTUS programme and enrolled patients with NVAF treated with rivaroxaban from Eastern Europe, the Middle East and Africa (EEMEA) and Latin America.MethodsPatients with NVAF starting rivaroxaban for stroke prevention were consecutively recruited and followed for 1 year, at approximately 3-month intervals, or for ≥30 days after permanent rivaroxaban discontinuation. Primary outcomes were major bleeding, adverse events (AEs), serious AEs and all-cause mortality. Secondary outcomes included stroke, non-central nervous system systemic embolism (non-CNS SE), transient ischaemic attack (TIA), myocardial infarction (MI) and non-major bleeding. All major outcomes were centrally adjudicated.ResultsOverall, 2064 patients were enrolled; mean age ± standard deviation was 67.1 ± 11.32 years; 49.3% were male. Co-morbidities included heart failure (30.9%), hypertension (84.2%), diabetes mellitus (26.5%), prior stroke/non-CNS SE/TIA (16.2%) and prior MI (10.7%). Mean CHADS2, CHA2DS2-VASc and HAS-BLED scores were 2.0, 3.6 and 1.6, respectively. Treatment-emergent event rates were (events/100 patient-years, [95% confidence interval]): major bleeding 0.9 (0.5–1.4); all-cause mortality 1.7 (1.2–2.4); stroke/non-CNS SE 0.7 (0.4–1.2); any AE 18.1 (16.2–20.1) and any serious AE 8.3 (7.0–9.7). One-year treatment persistence was 81.9%.ConclusionsXANTUS-EL confirmed low stroke and major bleeding rates in patients with NVAF from EEMEA and Latin America. The population was younger but with more heart failure and hypertension than XANTUS; stroke/SE rate was similar but major bleeding lower.

Embolic and Other Adverse Outcomes in Symptomatic Versus Asymptomatic Patients With Atrial Fibrillation (from the ORBIT-AF Registry)

Asymptomatic atrial fibrillation (AF) is being increasingly diagnosed via implantable devices, screening, and inpatient telemetry. Management of asymptomatic AF is controversial, in part, because the associated risks have not been well described. We examined the incidence of major adverse outcomes in patients with asymptomatic versus symptomatic AF using Outcomes Registry for Better Informed Treatment of Atrial, a nationwide US registry of AF patients. We compared stroke and/or non-central nervous system (CNS) embolism, major adverse cardiovascular and neurologic events, bleeding, and death in 9,319 asymptomatic (defined by European Heart Rhythm Association score = 1 or "no symptoms") versus symptomatic patients. Overall, median (interquartile) age was 75 (67 to 82) years, 3,944 (42%) were women, and 38% versus 37% were asymptomatic based on physician versus patient-reported symptoms. Compared with those with symptoms, physician-defined asymptomatic patients were less likely to be woman (35%/47%) or be on an antiarrhythmic agent (22%/33%), but were more likely to have permanent and/or persistent AF (51%/40%). CHA2DS2-VASc scores did not vary by symptom status. After adjustment, risk of first stroke and/or non-CNS embolism (hazard ratio [HR] 0.85 [95% confidence interval {CI} 0.63 to 1.16], p = 0.32), major adverse cardiovascular and neurologic events (HR 0.88 [95% CI 0.76 to 1.03], p = 0.11), bleeding (HR 0.85 [95% CI 0.72 to 1.00], p = 0.05), and death (HR 0.99 [95% CI 0.87 to 1.13], p = 0.88) were similar in asymptomatic (European Heart Rhythm Association = 1) and symptomatic AF, respectively. Prospective, randomized studies are needed to further define associated adverse events and delineate optimal prophylactic therapies in patients with asymptomatic AF.

Atrial fibrillation and ischemic events with rivaroxaban in patients with stable coronary artery disease (AFIRE): Protocol for a multicenter, prospective, randomized, open-label, parallel group study

BackgroundIn atrial fibrillation (AF) patients with coronary artery disease (CAD), anticoagulants are commonly used in combination with antiplatelet drugs. However, dual therapy can increase the risk of bleeding, and the potential therapeutic benefits must be weighed against this. Therefore, it is recommended that dual therapy is only used for a limited time, and that monotherapy with anticoagulants should start from 1 year after percutaneous coronary intervention (PCI). However, there is a lack of evidence on the use of monotherapy, in particular with direct oral anticoagulants, in this group of patients. MethodsThe AFIRE Study is a multicenter, prospective, randomized, open-label, parallel group study conducted in patients aged ≥20 years with non-valvular AF (NVAF) and CAD. Patients who have undergone PCI or coronary artery bypass graft at least 1 year prior to enrollment, or those without significant coronary lesions requiring PCI (≥50% stenosis), will be included. Approximately 2200 participants will be randomized to receive either rivaroxaban monotherapy or rivaroxaban plus an antiplatelet drug (aspirin, clopidogrel, or prasugrel). The primary efficacy endpoints are the composite of cardiovascular events (stroke, non-central nervous system embolism, myocardial infarction, and unstable angina pectoris requiring revascularizations) and all-cause mortality. The primary safety endpoint is major bleeding as defined by the International Society on Thrombosis and Haemostasis criteria. ConclusionsThis study will be the first to assess the efficacy and safety of rivaroxaban monotherapy in NVAF patients with stable CAD.

Understanding the Value of Real-World Evidence: Focus on Stroke Prevention in Atrial Fibrillation with Rivaroxaban.

Real-world data are a well-recognized component within the drug lifecycle, and such data are generated from a range of sources and study designs, including claims databases, electronic health records, non-interventional studies (NIS) and registries. While this information can be of vital clinical importance, there may be challenges in understanding the relevance of the differing study designs, endpoints and populations. Here, we summarize the value of real-world evidence and considerations pertinent to their use in clinical research. Owing to the variety of analyses being conducted using real-world data, it is important for researchers and clinicians to have a clear understanding of the nature and origin of those data, and to ensure they are valid, reliable and robust in terms of extrapolating meaningful findings. There are crucial questions to address when evaluating real-world studies, and we introduce a checklist to meet these objectives. In addition to advice for appraising data quality and study designs, several updates will be covered from real-world studies of rivaroxaban for stroke prevention in patients with atrial fibrillation (AF): the nationwide Danish cohort study, U.S. Department of Defense Military Health System database, retrospective claim database study REAFFIRM and a pooled analysis from the global NIS XArelto on preveNtion of sTroke and non-central nervoUS system systemic embolism in patients with non-valvular atrial fibrillation (XANTUS). Real-world studies consistently show that rivaroxaban is an effective treatment option with acceptable safety when used for stroke prevention in a large number of patients with AF across the globe.

Design and baseline characteristics of the Xarelto Post-Authorization Safety & Effectiveness Study in Japanese Patients with Atrial Fibrillation (XAPASS).

BackgroundThe phase III Japanese Rivaroxaban Once‐Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (J‐ROCKET AF) showed that the rivaroxaban group had a lower event rate of intracranial bleeding than the warfarin group and that rivaroxaban was noninferior to warfarin for the principal safety outcome. However, safety and effectiveness data from unselected patients with AF in everyday clinical practice in Japan are lacking.MethodsThe Xarelto Post‐Authorization Safety & Effectiveness Study in Japanese Patients with Atrial Fibrillation (XAPASS) is a real‐world, prospective, single‐arm, observational study mandated by the Japanese authority as postmarketing surveillance. XAPASS involves patients with nonvalvular AF prescribed rivaroxaban. The principal safety outcome is a composite of major and nonmajor bleeding events, and the primary effectiveness outcome is the incidence of ischemic stroke, hemorrhagic stroke, noncentral nervous system systemic embolism, and myocardial infarction.ResultsIn total, 11 308 patients were enrolled from April 2012 to June 2014. Their age was 73.1 ± 9.9 years, and their CHADS 2 score was 2.2 ± 1.3. Female patients, patients aged ≥75 years, patients with a body weight of ≤50 kg, and patients with a creatinine clearance of <50 mL/min constituted 38.1%, 48.7%, 19.5%, and 23.9% of all patients, respectively. Almost half (53.2%) of patients were prescribed other anticoagulants before starting rivaroxaban.ConclusionsData from this study will supplement those from the J‐ROCKET AF and provide practical information for the optimal use of rivaroxaban for stroke prevention in Japanese patients with AF (Clinicaltrials.gov: NCT01582737).

Abstract 12462: Improved Treatment Satisfaction Independent of Stroke and Bleeding Risk Among Patients Transitioned From a Vitamin K Antagonist to Rivaroxaban: A XANTUS-ACTS Analysis

Introduction: The effectiveness, safety and ease of use of rivaroxaban may reduce anticoagulation treatment burden and improve nonvalvular atrial fibrillation (NVAF) patient satisfaction compared to vitamin K antagonists (VKAs). Objective: To assess consistency in changes in treatment satisfaction among patients transitioned from a VKA to rivaroxaban in routine practice across stroke and bleeding risk subgroups. Methods: Xarelto on Prevention of Stroke and Non-Central Nervous System Systemic Embolism in Patients with Nonvalvular Atrial Fibrillation (XANTUS) was a prospective, non-interventional study in patients prescribed rivaroxaban for prevention of stroke in routine practice within 7 European countries and Canada. Patients receiving a VKA 4-weeks prior to the initial XANTUS study visit and switched to rivaroxaban were asked to complete the Anti-Clot Treatment Scale (ACTS). Changes in scores, as recorded during the initial and first follow-up visit at ~3-months (corresponding to a comparison of rivaroxaban vs. prior VKA) for the ACTS Burdens and Benefits scores, were calculated and reported as least squares (LS)-mean differences with standard errors. Results: After ~3-months’ rivaroxaban treatment, both Burdens and Benefits scores were significantly improved in NVAF patients with prior VKA treatment ( Table ). Improvements in Burden scores across subgroups were generally consistent (LS-mean difference range, 2.68 to 3.46) with the overall cohort findings. The Benefit score improved in the overall cohort, but was not found to significantly differ in any subgroup (LS-mean difference range, -0.26 to 0.58). Conclusions: In XANTUS, patients switching from a VKA to rivaroxaban for stroke prevention reported significant improvements in treatment satisfaction. Independent of stroke or bleeding risk, switching to rivaroxaban appears to improve patient treatment satisfaction; mainly due to a perceived lower treatment burden

The Efficacy and Safety of Edoxaban for VTE Prophylaxis Post-Orthopedic Surgery: A Systematic Review.

Venous thromboembolism (VTE) is a common complication that manifests during and/or after hospitalization, as well as postsurgeries including orthopedic surgeries. Edoxaban is a new oral direct factor Xa inhibitor that has been recently approved for treating VTE in patients who have already been treated with a parenteral anticoagulant and for the prevention of stroke and non-central nervous system systemic embolism in patients with nonvalvular atrial fibrillation. The purpose of this systematic review was to evaluate the safety and efficacy of edoxaban for VTE prophylaxis after lower limb orthopedic surgery. A comprehensive search was conducted in Google Scholar, PubMed, MEDLINE, and ScienceDirect to identify potential records, then titles, abstracts, and full texts were screened using the inclusion criteria to filter out irrelevant studies. Moreover, the data extraction and quality assessment were undertaken using standardized tools, and the results were narratively synthesized and presented in tables. Six studies were included in this systematic review after screening 2989 records. The majority of studies demonstrated a statistically significant reduction in VTE events in the edoxaban group(s) compared to the dalteparin, placebo, or enoxaparin groups (P < .05). The differences in VTE cases in some studies reached to approximately 50% favoring edoxaban 30 mg over the comparator (P < .05). However, other studies uncovered a statistically insignificant difference between edoxaban and the comparator "enoxaparin" when used for VTE prophylaxis (P > .05). On the other hand, although edoxaban found to cause more bleeding, the differences between edoxaban and the comparator are statistically insignificant (P > .05). This study helped to amalgamate evidence with regard to the use of edoxaban for VTE prophylaxis post-lower limb orthopedic surgery. In line with the results of the reviewed studies, edoxaban seems to be highly effective in reducing VTE post-lower limb orthopedic surgery.

Clinical characteristics and one year outcomes in Chinese atrial fibrillation patients with stable coronary artery disease: a population-based study.

BackgroundAtrial fibrillation (AF) and coronary artery disease (CAD) often coexist, however, the clinical characteristics and the impact of stable CAD on the outcomes in Chinese patients with AF has not been well understood.MethodsConsecutive AF patients in 20 hospitals in China from November 2008 to October 2011 were enrolled. The primary endpoints included 1-year all-cause mortality, stroke, non-central nervous system (non-CNS) embolism, and major bleeding.ResultsA total of 1947 AF patients were analyzed, of whom 40.5% had stable CAD. The mean CHADS2 scores in CAD patients were significantly higher than that of non-CAD patients (2.4 ± 1.4 vs. 1.4 ± 1.2, P < 0.001). During follow-up period, warfarin use is low in both groups, with relatively higher proportion in non-CAD patients compared with CAD patients (22.3% vs. 10.7%, P < 0.001). Compared with non-CAD patients, CAD patients had higher one-year all-cause mortality (16.8% vs. 12.9%, P = 0.017) and incidence of stroke (9.0% vs. 6.4%, P = 0.030), while the non-CNS embolism and major bleeding rates were comparable between the two groups. After multivariate adjustment, stable CAD was independently associated with increased risk of 1-year all-cause mortality (HR = 1.35, 95% CI: 1.01−1 .80, P = 0.040), but not associated with stroke (HR = 1.07, 95% CI: 0.72–1.58, P = 0.736).ConclusionsStable CAD was prevalent in Chinese AF patients and was independently associated with increased risk of 1-year all-cause mortality. Chinese AF patients with stable CAD received inadequate antithrombotic therapy and this grim status of antithrombotic therapy needed to be improved urgently.

Direct oral factor Xa inhibitors for the prevention of non-central nervous systemic embolism patients with non-valvular atrial fibrillation - a systematic review and meta-analysis.

The aim of this systematic review and meta-analysis was to evaluate the efficacy of direct oral factor Xa inhibitors for preventing non-central nervous systemic embolism in patients with non-valvular atrial fibrillation. We conducted a systematic review of the following databases: Ovid MEDLINE, EUROPUBMED, EMBASE, and the Cochrane Central Register of Controlled Trials, from July 1st 1990 to April 1st, 2015. Randomised controlled trials were included if they reported the outcomes of patients with non-valvular atrial fibrillation treated with a direct oral factor Xa inhibitors compared to a vitamin K antagonist. The primary outcome was objectively confirmed as non-central nervous systemic embolism and ischaemic stroke was the secondary outcome. The random-effects model odds ratio was used as the outcome measure. Our initial search identified 987 relevant articles, of which three satisfied our inclusion criteria and were included. Compared to vitamin K antagonists targeting an INR between 2 and 3, direct oral factor Xa inhibitors alone did not reduce the incidence of non-central nervous systemic embolism [OR 0.63 (95 % CI 0.30 - 1.35)] or ischaemic stroke [OR 1.06 (95 % CI 0.86 - 1.32)]. As a drug class, direct oral factor Xa inhibitors do not reduce the incidence of non-central nervous systemic embolism (or ischaemic stroke) in patients with non-valvular atrial fibrillation. Selecting drugs for the prevention of non-central nervous systemic embolism in patients with non-valvular atrial fibrillation should be based on individual drug efficacy data, rather than class data.

Differences in Clinical and Functional Outcomes of Atrial Fibrillation in Women and Men: Two-Year Results From the ORBIT-AF Registry.

Despite the frequency of atrial fibrillation (AF) in clinical practice, relatively little is known about sex differences in symptoms and quality of life and how they may affect treatment and outcomes. To determine whether symptoms, quality of life, treatment, and outcomes differ between women and men with AF. This observational cohort study included 10 135 patients with AF. The Outcomes Registry for Better Informed Treatment of Atrial Fibrillation is a prospective, nationwide, multicenter outpatient registry of patients with incident and prevalent AF enrolled at 176 sites between June 2010 and August 2011. Symptoms, quality of life as measured by Atrial Fibrillation Effects on Quality of Life scores, AF treatment, cardiovascular outcomes, stroke or non-central nervous system embolism, and all-cause mortality. Overall, 4293 of the cohort (42%) were female. Compared with men, women were older (77 years; interquartile range [IQR], 69-83, vs 73 years; IQR, 65-80; P < .001) and had higher median CHA2DS2-VASc scores (5; IQR, 4-6, vs 3; IQR, 2-5; P < .001), but less sleep apnea (578 [13.5%] vs 1264 [21.6%]; P < .001). Only 32.1% of women (n = 1378) were asymptomatic (European Heart Rhythm Association class I) compared with 42.5% of men (n = 2483) in unadjusted analyses (P < .001). Women had lower (more severe) unadjusted baseline overall Atrial Fibrillation Effects on Quality of Life scores (n = 2007; 80; IQR, 62-92 vs 83; IQR, 69-94; P < .001). Women had similar rates of anticoagulation and similar time in therapeutic range. In follow-up, women experienced lower risk-adjusted all-cause mortality (adjusted hazard ratio, 0.57; 95% CI, 0.49-0.67) and cardiovascular death (adjusted hazard ratio, 0.56; 95% CI, 0.44-0.72); however, they had a higher risk for stroke or non-central nervous system embolism (adjusted hazard ratio, 1.39; 95% CI, 1.05-1.84; P = .02) compared with men. Women with AF have more symptoms and worse quality of life. Despite higher risk, women have lower risk-adjusted all-cause and cardiovascular death compared with men, but higher stroke rates. Future studies should focus on how treatment and interventions specifically affect AF-related quality of life and cardiovascular outcomes in women. clinicaltrials.gov Identifier: NCT01165710.