The impact of ABCB1, CYP3A4/5 and ABCG2 gene polymorphisms on rivaroxaban trough concentrations and bleeding events in patients with non-valvular atrial fibrillation.

BACKGROUND: The influence of genetic factors on the pharmacokinetics and clinical outcomes of rivaroxaban in patients with non-valvular atrial fibrillation (NVAF) is poorly understood. This study aimed to explore the effects of CYP3A4/5, ABCB1, and ABCG2 gene polymorphisms on the trough concentrations and the bleeding risk of rivaroxaban in NVAF patients. PATIENTS AND METHODS: This study is a prospective multicenter study. The patient's blood samples were collected to detect the steady-state trough concentrations of rivaroxaban and gene polymorphisms. We visited the patients regularly at month 1, 3, 6, and 12 to record bleeding events and medications. RESULTS: A total of 95 patients were enrolled in this study, and 9 gene loci were detected. For the dose-adjusted trough concentration ratio (Ctrough/D) of rivaroxaban, the homozygous mutant type was significantly lower than wild type at ABCB1 rs4148738 locus (TT vs. CC, P = 0.033), and the mutant type was significantly lower than the wild type at ABCB1 rs4728709 locus (AA + GA vs. GG, P = 0.008). ABCB1 (rs1045642, rs1128503), CYP3A4 (rs2242480, rs4646437), CYP3A5 (rs776746), and ABCG2 (rs2231137, rs2231142) gene polymorphisms had no significant effect on the Ctrough/D of rivaroxaban. For the bleeding events, we found that there were no significant differences among genotypes of all gene loci. CONCLUSION: This study found for the first time that ABCB1 rs4148738 and rs4728709 gene polymorphisms had a significant impact on the Ctrough/D of rivaroxaban in NVAF patients. CYP3A4/5, ABCB1, and ABCG2 gene polymorphisms were not associated with the bleeding risk of rivaroxaban.

Asymmetric Dimethylarginine Is Associated with the Phenomenon of Coronary Slow Flow in Patients with Nonvalvular Atrial Fibrillation.

INTRODUCTION: Coronary slow flow phenomena (CSFP) are associated with endothelial and blood component abnormalities in coronary arteries. Asymmetric dimethylarginine (ADMA) can damage the endothelium of the heart or blood vessels in patients with non-valvular atrial fibrillation (NVAF), causing changes in levels of biological indicators. Our aim was to analyze the relationship between ADMA and CSFP in NVAF patients. METHODS: We consecutively enrolled 134 patients diagnosed with NVAF and underwent coronary angiography, 50 control patients without a history of atrial fibrillation and with normal coronary angiographic flow were included at the same time. Based on the corrected TIMI frame count (CTFC), the NVAF patients were categorized into two groups, CTFC ≤27 frames and CTFC >27 frames. Plasma ADMA, P-selectin (p-sel), von Willebrand factor (vWF), D-dimer (D-Di), plasminogen activator inhibitor 1 (PAI-1), and nitric oxide (NO) were detected by ELISA in the different groups. RESULTS: We found that plasma ADMA levels were significantly higher among NVAF patients in the CTFC >27 grade group compared with the control or CTFC ≤27 group. In addition, the levels of blood cells and endothelium-related biomarkers (NO, P-selectin, vWF, D-Di, and PAI-1) were significantly altered and correlated with ADMA levels. Multifactorial analysis showed that plasma ADMA (odd ratio [OR; 95% CI]: 1.65 [1.21-2.43], p < 0.001) and left atrial internal diameter (OR [95% CI]: 1.04 [1.02, 1.1], p < 0.001) could be used as independent risk factors for the development of CSFP in patients with NVAF. The ROC curves of ADMA can predict the development of CSFP in NVAF patients. The minimum diagnostic concentration for the development of CSFP in patients was 2.31 µmol/L. CONCLUSION: Our study demonstrated that CSFP in NVAF patients was associated with high levels of ADMA and left atrial internal diameter. Therefore, aggressive preoperative detection and evaluation of ADMA and left atrial internal diameter can help deal with the intraoperative presence of CSFP.

Effectiveness and safety in non-valvular atrial fibrillation patients switching from warfarin to direct oral anticoagulants in US healthcare claims.

INTRODUCTION: There is a paucity of real-world studies examining the risks of stroke/systemic embolism (SE) and major bleeding (MB) among non-valvular atrial fibrillation (NVAF) patients switching from warfarin to a direct oral anticoagulant (DOAC). This retrospective study was conducted to compare the stroke/SE and MB risks between patients switched from warfarin to apixaban, dabigatran, or rivaroxaban in real-world clinical practice. MATERIALS AND METHODS: This study used data from four United States commercial claims databases from January 1, 2012 to June 30, 2019. The study population included NVAF patients initially treated with warfarin and switched to apixaban, dabigatran, or rivaroxaban within 90 days of their warfarin prescription ending. Patients were matched 1:1 between the DOACs in each database using propensity scores and then pooled for the final analysis. Cox proportional hazards models were used to calculate the risk of stroke/SE and MB. RESULTS AND CONCLUSIONS: The final population consisted of 2,611 apixaban-dabigatran, 12,165 apixaban-rivaroxaban, and 2,672 dabigatran-rivaroxaban pairs. Apixaban vs. dabigatran was associated with a lower risk of stroke/SE (hazard ratio [HR]: 0.61; 95% confidence interval [CI]: 0.39-0.96) and MB (HR: 0.67; 95% CI: 0.50-0.91). Apixaban vs. rivaroxaban was associated with a similar risk of stroke/SE (HR: 0.88; 95% CI: 0.73-1.07) and a lower risk of MB (HR: 0.60; 95% CI: 0.52-0.68). There was no significant difference in either risk between dabigatran and rivaroxaban. These results provide important insights into how the risks of stroke/SE and MB for NVAF patients vary when switching from warfarin to different DOACs.

Left atrial volume index as a predictor for left atrial appendage thrombus in patients with non-valvular atrial fibrillation receiving appropriate oral anticoagulation therapy: A prospective multi-center study.

OBJECTIVES: We previously reported a higher left atrial volume index (LAVI) was independently associated with left atrial (LA) appendage (LAA) thrombus formation in 737 patients with non-valvular atrial fibrillation (NVAF) receiving appropriate oral anticoagulation therapy. Since our previous study was a retrospective single-center study, we designed and conducted a prospective multi-center study to verify our findings for LAVI as a predictor of LAA thrombus in patients with NVAF receiving appropriate oral anticoagulation therapy. METHODS: This prospective multi-center study comprised 746 consecutive patients with NVAF recruited between December 2021 and March 2023 from eight institutions in Japan, who were receiving appropriate oral anticoagulation therapy, had undergone transthoracic echocardiography and transesophageal echocardiography (TEE). RESULTS: LAA thrombi were observed in 21 patients (2.8%). The prevalence of LAA thrombus formation in patients with paroxysmal AF (PAF) was significantly lower than that in patients with non-PAF (0.7% vs. 4.1%, p = .006). LAA thrombus formation was detected in none (0/171) of the patients with normal size LA (LAVI ≤ 34 mL/m2 ). The prevalence of LAA thrombus formation in patients with mildly dilated LA (LAVI: 34-49.9 mL/m2 ) was 2.1% (6/283), but that in PAF patients was low at 1.0% (1/104). Furthermore, this prevalence in patients with severely dilated LA (LAVI ≥ 50 mL/m2 ) was high at 5.1% (15/292). CONCLUSIONS: The findings of this prospective multi-center study are consistent with those of our previous study. Thus, the need for TEE prior to catheter ablation or electrical cardioversion can be determined by the level of LAVI.

The value of combined detection D-dimer and NLR in judging the severity and short-term prognosis of acute cardiogenic cerebral embolism in elderly patients.

OBJECTIVE: To assess the utility of combined neutrophil-to-lymphocyte ratio (NLR) and D-dimer detection in determining the severity and short-term prognosis of acute cardiogenic cerebral embolism (ACCE) in older adults. METHODS: We selected 202 elderly non-valvular atrial fibrillation patients hospitalized at the Third Affiliated Hospital of Anhui Medical University from April 1, 2020, to April 1, 2023. They were divided into an observation group (69 cases combined with ACCE) and a control group (133 cases with non-valvular atrial fibrillation alone) based on whether acute cardioembolic cerebral embolism occurred. According to the National Institutes of Health Stroke Scale (NIHSS), the observation group was divided into a mild cerebral infarction group (MICI group), a moderate cerebral infarction group (MOCI group), and a severe cerebral infarction group (SCI group), with 26 cases, 29 cases, and 14 cases, respectively. According to the modified Rankin scale (mRS), after 3 months, 30 cases were divided into the good prognosis group and 39 cases were divided into the poor prognosis group. We detected and compared the differences in D-dimer and NLR levels among different groups of patients, as well as differences in some important laboratory indicators. Logistic regression analysis was used to identify factors influencing the short-term prognosis of patients with acute cardioembolic cerebral infarction, and ROC curves were plotted to evaluate the value of D-dimer and NLR in predicting the short-term prognosis of patients with acute cardioembolic cerebral infarction. RESULTS: The levels of D-dimer and NLR in peripheral blood in SCI group [1.82 (0.58-6.71) mg/l, 4.55 (3.14,7.21)] were higher than those in MOCI group [1.16 (0.65-1.90) mg/l, 3.84 (2.31,6.68)] and MICI group [0.53 (0.32-0.90) mg/l, 2.46 (2.09-3.79)]. The difference between groups was statistically significant (P < 0.05). Logistic regression analysis showed that D-dimer and NLR were independent risk factors for poor prognosis in patients with acute cardiogenic cerebral embolism (OR values were 1.772 and 1.603, and 95 %CI were 1.060-2.963 and 1.100-2.338, respectively, both P < 0.05). The AUC for the prediction of poor prognosis in acute cardioembolic stroke by combining D-dimer and NLR was 0.812 [95 % CI: 0.710-0.914], higher than the individual detections of D-dimer at 0.756 [95% CI: 0.642-0.869] and NLR at 0.733 [95 % CI: 0.613-0.854]. CONCLUSION: Peripheral blood D-dimer combined with NLR detection is helpful for the risk stratification and short-term prognosis assessment of patients with acute cardiogenic cerebral embolism. Clinical detection is of great significance for the prevention and monitoring of disease development.

Causes of Death in Elderly Patients With Non-Valvular Atrial Fibrillation　- Results From the ANAFIE Registry.

BACKGROUND: Previous studies on mortality in atrial fibrillation (AF) included a limited number of elderly patients receiving direct oral anticoagulants (DOACs). This subanalysis of the ANAFIE Registry evaluated 2-year mortality according to causes of death of elderly non-valvular AF (NVAF) patients in the DOAC era.Methods and Results: The ANAFIE Registry was a multicenter prospective observational study. Mean patient age was 81.5 years and 57.3% of patients were male. Of the 32,275 patients completing the study, 2,242 died. The most frequent causes of death were cardiovascular (CV) death (32.4%), followed by infection (17.1%) and malignancy (16.1%). Incidence rates of CV-, malignancy-, and infection-related death were 1.20, 0.60, and 0.63 per 100 person-years, respectively. Patients aged ≥85 years showed increased proportions of non-CV and non-malignancy deaths and a decreased proportion of malignancy deaths compared with patients aged <85 years. The incidence of death due to congestive heart failure/cardiogenic shock, infection, and renal disease was higher in patients aged ≥85 than those aged <85 years. Compared with warfarin, DOACs were associated with a significantly lower risk of death by intracranial hemorrhage, ischemic stroke, and renal disease. CONCLUSIONS: This subanalysis described the mortality according to causes of death of Japanese elderly NVAF patients in the DOAC era. Our results imply that a more holistic approach to comorbid conditions and stroke prevention are required in these patients.

Relationship Between Direct Oral Anticoagulant Doses and Clinical Outcomes in Elderly Patients With Non-Valvular Atrial Fibrillation　- ANAFIE Registry Sub-Analysis.

BACKGROUND: This sub-analysis of the ANAFIE Registry, a prospective, observational study of >30,000 Japanese non-valvular atrial fibrillation (NVAF) patients aged ≥75 years, assessed the prevalence of direct oral anticoagulant (DOAC) under-dose prevalence, identified the factors of under-dose prescriptions, and examined the relationship between DOAC dose and clinical outcomes.Methods and Results: Patients, divided into 5 groups by DOAC dose (standard, over-, reduced, under-, and off-label), were analyzed for background factors, cumulative incidences, and clinical outcome risk. Endpoints were stroke/systemic embolic events (SEE), major bleeding, and all-cause death during the 2-year follow-up. Of 18,497 patients taking DOACs, 20.7%, 3.8%, 51.6%, 19.6%, and 4.3%, were prescribed standard, over-, reduced, under-, and off-label doses. Factors associated with under-dose use were female sex, age ≥85 years, reduced creatinine clearance, history of major bleeding, polypharmacy, antiplatelet agents, heart failure, dementia, and no history of catheter ablation or cerebrovascular disease. After confounder adjustment, under-dose vs. standard dose was not associated with the incidence of stroke/SEE or major bleeding but was associated with a higher mortality rate. Patients receiving an off-label dose showed similar tendencies to those receiving an under-dose; that is, they showed the highest mortality rates for stroke/SEE, major bleeding, and all-cause death. CONCLUSIONS: Inappropriate low DOAC doses (under- or off-label dose) were not associated with stroke/SEE or major bleeding but were associated with all-cause death.

Safety and efficacy of direct oral anticoagulation in patients with and without radiofrequency ablation of non-valvular atrial fibrillation: a multicenter retrospective cohort study.

BACKGROUND: Based on the few available studies on the prognostic benefit of using direct oral anticoagulants (DOACs) after atrial fibrillation (AF) ablation. Therefore, this study aimed to evaluate the prognostic differences between patients who underwent radiofrequency ablation (RFA) and those without RFA taking DOACs. METHODS: This is a multicenter retrospective cohort study enrolling 6137 patients with non-valvular AF (NVAF) at 15 hospitals in China. Patient information was collected through a mean follow-up of 10 months and medical record queries. Clinical outcomes included major bleeding, total bleeding, thrombosis, all-cause death, and a composite endpoint of bleeding, thrombosis, and all-cause death. RESULTS: After adjusting for confounders and propensity score matching (PSM), patients with RFA of NVAF had a significantly lower risk of major bleeding [OR 0.278 (95% CI, 0.150-0.515), P<0.001], thrombosis [OR 0.535 (95% CI, 0.316-0.908), P=0.020] and the composite endpoint [ OR 0.835 (95% CI, 0.710-0.982), P=0.029]. In the RFA PSM cohort, dabigatran was associated with reduced all-cause death in patients with RFA of NVAF [OR 0.420 (95% CI, 0.212-0.831), P=0.010]. In the no RFA PSM cohort, rivaroxaban was associated with a reduction in major bleeding [OR 0.521 (95% CI, 0.403-0.673), P<0.001], total bleeding [OR 0.114 (95% CI, 0.049-0.266), P<0.001], and the composite endpoint [OR 0.659 ( 95% CI, 0.535-0.811), P<0.001]. CONCLUSION: Among patients with NVAF treated with DOACs, RFA was a negative correlate of major bleeding, thrombosis, and composite endpoints but was not associated with total bleeding or all-cause mortality.

3-Year outcomes after left atrial appendage closure in patients with nonvalvular atrial fibrillation: cardiomyopathy related with increased death and stroke rate.

INTRODUCTION: Left atrial appendage closure (LAAC) is a novel treatment for stroke prevention in high-risk patients with non-valvular atrial fibrillation (NVAF). However, the long-term outcomes after LAAC in Chinese NVAF patients are still lacking. METHODS: This was a single-center, bidirectional, nonrandomized registered study. Patients who underwent LAAC implantation from May 2014 to April 2021 in a large Chinese center were enrolled. The primary endpoint was combined all-cause death and stroke. RESULTS: From May 2014 to April 2021, a total of 673 NVAF patients were enrolled. The overall successful implantation rate was 97.62% (657 of 673). The rate of perioperative adverse events was 1.19% (8 of 673), including 3 cardiac tamponades, 2 ischemic strokes, one device-related thrombus (DRT) and 2 device dislocations. 604 (92.24%) patients completed the follow-up, the median follow-up period was 36.9 months (IQR 24.8-56.5 months). 16 stroke events occurred in 15 patients (one patient suffered from both hemorrhagic and ischemic strokes). 13 patients (2.15%) had ischemic stroke, and the fatal rate was 0.33% (2 of 604). 3 patients (0.15%) suffered from hemorrhagic stroke, and the fatal rate was 0.17% (1 of 604). The overall stroke rate was 0.74% per-year. The combined death and stroke rate was 1.93% per-year. In the multivariate Cox regression analysis, age ≥ 75 (hazard ratio 2.264, 95% CI 1.074-4.772, P = 0.032) and ventricular cardiomyopathy (hazard ratio 2.738, 95% CI 1.060-7.071, P = 0.037) were independent predictors of combined mortality and stroke. CONCLUSION: The overall successful implantation rate of LAAC was 97.62% and the rate of perioperative adverse events was 1.19% in this study, and the stroke rate was 0.74% per year during the long-term follow-up. Age ≥ 75 years and ventricular cardiomyopathy were independent predictors of the primary endpoint. Trial registration This study was retrospectively registered.

Predicting a decrease in left atrial appendage flow velocity using left atrial diameter and CHA2DS2-VASc score in patients with non-valvular atrial fibrillation.

BACKGROUND: Left atrial (LA) appendage flow velocity (LAAFV) is a classic but invasive predictor of thromboembolic events in patients with atrial fibrillation (AF). We aimed to explore the usefulness of LA diameter (LAD) combined with CHA2DS2-VASc score, which is easily available and non-invasive, as a novel score for predicting a decrease in LAAFV in non-valvular AF (NVAF). METHODS: In total, 716 consecutive NVAF patients who underwent transesophageal echocardiography were divided into the decreased LAAFV (< 0.4 m/s) and preserved LAAFV (≥ 0.4 m/s) groups. RESULTS: The decreased LAAFV group had a larger LAD and a higher CHA2DS2-VASc score than the preserved LAAFV group (P < 0.001). Multivariate linear regression indicated that brain natriuretic peptide (BNP) concentration, persistent AF, LAD, and CHA2DS2-VASc score were remained inversely associated with LAAFV. Moreover, multivariate logistic regression revealed that BNP concentration (odds ratio [OR] 1.003, 95% confidence interval [CI] 1.001-1.005, P = 0.003), persistent AF (OR 0.159, 95% CI 0.102-0.247, P < 0.001), and LAD (OR 1.098, 95% CI 1.049-1.149, P < 0.001) were independent factors for a decrease in LAAFV. A novel score, LAD combined with CHA2DS2-VASc score, was more accurate for predicting a decrease in LAAFV among NVAF patients (area under the curve was 0.733). CONCLUSION: Enlarged LAD was independent risk factor for a decrease in LAAFV among NVAF patients. LAD combined with CHA2DS2-VASc score enhanced the predictive ability for a decrease in LAAFV among NVAF patients.

The novel left atrial appendage strain parameters are associated with thrombosis risk in patients with non-valvular atrial fibrillation.

OBJECTIVES: We sought to explore a novel left atrial appendage (LAA) strain parameter which could represent the cumulative adverse impact of chronic Atrial fibrillation (AF) on the LAA function, and the relationship between the LAA strain parameter and thrombosis risk in patients with non-valvular AF. METHODS: We enrolled 268 patients with non-valvular AF and 58 sinus rhythm subjects who underwent transesophageal echocardiography in the study. LAA longitudinal strain amplitude (LAA LSA) was defined as the sum of the value of the maximum positive peak strain (LAA PLS) and the absolute value of the minimum negative peak strain (LAA NLS). Dense spontaneous echo contrast (SEC) was defined as grade 3 or 4 SEC. RESULTS: Compared to sinus rhythm group, the global LAA strain parameters were significantly lower in paroxysmal AF (n = 148), and the lowest of them were found in persistent AF (n = 120), which suggested that the global LAA strain parameters could evaluate LAA function in sinus rhythm, paroxysmal AF and persistent AF. Compared with patients in AF without SEC/thrombus (n = 113), the regional and global LAA strain parameters were significantly depressed in AF with SEC/thrombus (n = 155). Multivariate logistic regression analyses showed that LAA global LSA (OR 0.768; 95% CI:0.569, 0.970; p = 0.027) was an independent predicter of the SEC/thrombus. Compared with patients in AF without dense SEC or thrombus (n = 210), the regional and global LAA strain parameters were significantly impaired in the patients with dense SEC/thrombus(n = 58). LAA global LSA (AUC 0.884) had the best predictable accuracy for dense SEC or thrombus, and outperformed LAA PLS, LAA NLS, CHA2DS2-VASc score and conventional LAA functional parameters that have been used in the evaluation blood flow stasis in LAA. LAA LSA showed excellent interobserver and intra-observer agreement beyond LAA PLS and LAA NLS. CONCLUSION: The novel LAA strain parameters, which were feasible and reproducible parameters for evaluation LAA mechanic function, had good predictive accuracy for blood flow stasis in LAA beyond conventional LAA functional parameters.

Changing trends and factors influencing anticoagulant use in patients with acute ischemic stroke and NVAF at discharge in the NOACs era.

OBJECTIVES: We sought to explore the trends and influencing factors of the use of anticoagulants in patients with acute ischemic stroke and non-valvular atrial fibrillation (NVAF) at discharge in the era of novel oral anticoagulants (NOACs). METHODS: We recruited consecutive inpatients with acute ischemic stroke and NVAF in a registered study (NCT04080830) from January 2016 to December 2021. The relevant data of patients were collected. We compared the proportions of anticoagulant treatment at discharge before and after NOACs entered China's medical insurance system. The proportion of each antithrombotic status as well as anticoagulant agents at discharge in every year were calculated, and the trends during the study period were analyzed. The relevant factors affecting anticoagulant use at discharge were further analyzed. RESULTS: The proportion of anticoagulation at discharge increased significantly after NOACs entered China's medical insurance system in 2018 versus before (χ2 = 42.828, P < 0.001). There were statistically significant differences in antithrombotic status (χ2 = 69.954, P < 0.001) and in the proportion of different anticoagulant drugs (χ2 = 63.049, P<0.001) by year. Anticoagulant therapy (χ2 = 1.55, P = 0.671) and NOACs (χ2 = .178, P = 0.243) increased over 2016-2018 but was relatively stable during 2018-2021. Multivariate logistic regression analysis showed that age ≥75 years, coexisting cerebral artery stenosis, massive cerebral infarction and hemorrhagic transformation were independent risk factors affecting anticoagulants use (all P < 0.05). CONCLUSION: NOACs have indeed improved anticoagulants use in patients with acute ischemic stroke and NVAF at discharge. However, some specific factors affect anticoagulation therapy use at discharge and hinder further improvement even in the NOACs era.

Comparative Bleeding Risk in Patients with Atrial Fibrillation with Cancer versus Without Cancer from Nationwide Prospective Cohort.

Comparison of the bleeding risk for long-term oral anticoagulation (OAC) in patients with nonvalvular atrial fibrillation (AF) with and without cancers has been inconsistent. This study aimed to clarify the differences in the bleeding risk in patients with AF with cancers and those without cancers during the long-term OAC.The CODE-AF prospective registry enrolled 5,902 consecutive patients treated for AF at 10 tertiary referral centers in Korea. Of the enrolled patients, 464 (7.8%) were diagnosed with cancers and were followed for all stroke and bleeding events (net composite events).The age, CHA2DS2-VASC, and HAS-BLED scores were similar between AF patients with and without cancers. Male population greatly comprised patients with AF with cancers. They were equally prescribed with direct OAC compared to those without cancers. The incidence rate for clinically relevant nonmajor (CRNM) bleeding events was higher in the patients with AF with cancers than in those without cancers (4.4 per 100 person-years versus 2.8 per 100 person-years, P = 0.023), and net composite events were also more frequent in patients with AF with cancers than in those without cancers (6.4 per 100 person-years versus 4.0 per 100 person-years, P = 0.004). Patients with AF with cancers showed a significantly higher rate of CRNM bleeding (hazard ratio [HR] 1.54, confidence interval [CI] 1.05-2.25, P = 0.002) than those without cancers.Based on the AF cohort, AF with cancers could face a significantly higher risk for CRNM bleeding events in the long-term OAC than those without cancers.

Effects of the theory of planned behavior and nudge strategy-based intervention on the adherence to anticoagulation treatment in patients with non-valvular atrial fibrillation.

BACKGROUND: Non-valvular atrial fibrillation is associated with the incidence of thromboembolism. Current guidelines recommend preferential use of novel oral anticoagulants (NOAC) in patients with nonvalvular atrial fibrillation. Oral anticoagulation medication adherence rate was relatively low among discharged patients with non-valvular atrial fibrillation. AIM: To investigate the effects of the anticoagulation programs based on the theory of planned behavior and nudge strategy among patients with non-valvular atrial fibrillation. METHODS: 130 patients with non-valvular atrial fibrillation were randomized to the intervention group or control group, 72 patients in the intervention group, and 58 patients in the control group with a 6-month follow-up. Medication adherence, intention, attitude, perceived behavioral control and subjective norm and quality of life were assessed. RESULTS: There were significantly differences in the intention, attitude and subjective norm between the two groups at one month, three months and six months follow-up (P <0.01). There were significantly differences in the perceived behavioral control between the two groups at three months and six months follow-up (P <0.01). The medication adherence scale score was higher in the intervention group than in the control group at three months and six months follow-up. However, there were no differences in quality of life between the two groups at one month, three months and six months follow-up. CONCLUSIONS: The program based on the theory of planned behavior and nudge strategy can improve medication adherence in patients with non-valvular atrial fibrillation.

Major Hemorrhage Risk Associated with Direct Oral Anticoagulants in Non-Valvular Atrial Fibrillation: A Systematic Review and Meta-Analysis.

Background: Real-world, observational studies have investigated the safety profile of Direct Oral Anticoagulants (DOACs) on Major Hemorrhage (MH) used for stroke prevention in Non-Valvular Atrial Fibrillation (NVAF). We performed a systematic review and meta-analysis to investigate the comparative safety of DOACs versus other DOACs and versus Vitamin K Antagonists (VKAs) adhering to PRISMA guidelines. We defined MH according to the International Society on Thrombosis and Haemostasis statement or as the composite outcome of intracranial, gastrointestinal, genitourinary, respiratory, cavitary and musculoskeletal bleeding in case of studies using International Statistical Classification of Diseases codes for patient selection. Methods: We systematically investigated two databases (Medline, Embase) until April of 2021, gathered observational studies and extracted hazard ratios (HRs) with 95% confidence intervals (CI) on our outcome of interest. Additional subgroup analyses according to DOAC dosing, prior diagnosis of chronic kidney disease, prior diagnosis of stroke, history of previous use of VKA, the users' age, the users' gender and study population geographic region were conducted. All analyses were performed with a random-effects model. Results: From this search, 55 studies were included and 76 comparisons were performed. The MH risk associated with Rivaroxaban use was higher than the risk with Dabigatran use (HR: 1.32, 95% CI: 1.21-1.45, I 2 : 12.39%) but similar to VKA use (HR: 0.94, 95% CI: 0.87-1.02, I 2 : 76.57%). The MH risk associated with Dabigatran use was lower than the risk with VKA use (HR: 0.75, 95% CI: 0.64-0.90, I 2 : 87.57%). The MH risk associated with Apixaban use was lower than the risk with Dabigatran use (HR: 0.75, 95% CI: 0.64-0.88, I 2 : 58.66%), with Rivaroxaban use (HR: 0.58, 95% CI: 0.50-0.68, I 2 : 74.16%) and with VKA use (HR: 0.60, 95% CI: 0.55-0.65, I 2 : 58.83%). Our aforementioned subgroup analyses revealed similar results. Conclusions: All in all, Apixaban was associated with a reduced MH risk compared to Dabigatran, Rivaroxaban and VKA. Dabigatran was associated with a reduced MH risk compared to both Rivaroxaban and VKA.

Catheter Ablation Energy Sources and Myocardial Injury and Coagulation Biomarkers During Uninterrupted Periprocedural Edoxaban Use　- A Subanalysis of KYU-RABLE.

BACKGROUND: The effects of catheter ablation (CA) energy sources on myocardial injury and coagulation biomarkers among Japanese non-valvular atrial fibrillation patients receiving uninterrupted periprocedural edoxaban are unclear. This KYU-RABLE exploratory subanalysis compared the effects of CA using radiofrequency energy vs. cryoballoon on: (1) myocardial injury; and (2) plasma edoxaban and coagulation biomarker concentrations measured before and after CA.Methods and Results:Plasma creatine kinase (CK), edoxaban, D-dimer, and prothrombin fragment 1+2 (F1+2) concentrations within 1 h before CA were compared with concentrations the day after. All biomarkers increased after CA, regardless of the energy source, but especially with cryoballoon. Significantly higher increases in CK concentrations from before to the day after CA were seen with cryoballoon compared with radiofrequency energy (P<0.0001). Edoxaban concentrations were similar in both groups. Concentrations of D-dimer and F1+2 increased in both groups, but were significantly higher in the cryoballoon group (P<0.0001 and P=0.006, respectively). There were no significant between-group differences in the incidence of thrombotic or bleeding events. CONCLUSIONS: Uninterrupted edoxaban concentrations were similar in both groups. Both myocardial injury and coagulation biomarkers increased after CA, especially with cryoballoon, but there was no difference in the incidence of thrombotic or bleeding events. These findings suggest the efficacy of uninterrupted edoxaban, regardless of the CA energy source. Periprocedural anticoagulation, particularly with cryoballoon, should be undertaken with care.

A nomogram to predict left atrial appendage thrombus and spontaneous echo contrast in non-valvular atrial fibrillation patients.

BACKGROUND: Non-valvular atrial fibrillation (NVAF) significantly increases the risk of stroke. Although there is availability of prediction models, their ability to predict the risk of stroke in NVAF patients remains suboptimal. Therefore, there is need to improve prediction of high-risk individuals, which is critical for efficient management of patients with NVAF. OBJECTIVE: The objective of our paper is to develop a nomogram for predicting the risk of left atrial appendage thrombus (LAAT) and spontaneous echo contrast (SEC), thereby replacing the risk of stroke in NVAF patients. DESIGN: This was a retrospective cohort study that analyzed clinical data and echocardiographic indices of 387 patients with NVAF from October 2018 to June 2021. Multivariable logistic regression was used to evaluate independent factors that were used to construct the prediction nomogram. ANALYSIS: The discriminative ability and calibration of the nomogram to predict LAAT/SEC were tested using C-statistic and calibration plot. The performance of the nomogram was assessed against the CHA2DS2 score, CHA2DS2-VASc score and ATRIA score using the receiver operating characteristic curve (ROC), decision curve analysis (DCA), integrated discrimination index (IDI) and net reclassification index (NRI). RESULT: Out of the total 387 patients enrolled in this study, 232 had LAAT/SEC. Multivariable analyses demonstrated that N-terminal pro-B-type natriuretic peptide (NT-proBNP), albumin (ALB), LAA ejection fraction (LAAEF) and LAA global peak longitudinal strain (LAA GPLS) were independent predictors of LAAT/SEC. The constructed nomogram had good discriminative (C = 0.886) and calibration (0.876) abilities after bias correction by the C-index. Compared with other models, the decision curve analyses demonstrated that the nomogram had greater net benefits. Besides, the nomogram had significant improvement in predictive performance, sensitivity and reclassification for LAAT/SEC compared with the CHA2DS2 [(c-index: 0.886 vs. 0.576, p < 0.05), (NRI: 0.539, p < 0.05), (IDI: 0.432, p < 0.05)], CHA2DS2-VASc [(c-index: 0.886 vs0.579, p < 0.05), (NRI: 0.513, p < 0.05), (IDI: 0.432, p < 0.05)] or ATRIA [(c-index: 0.886 vs0.583, p < 0.05), (NRI: 0.546, p < 0.05), (IDI: 0.432, p < 0.05)]. CONCLUSION: Taken together, our data demonstrated that the developed nomogram was effective and had potential clinical application in the prediction of LAAT/SEC in patients with NVAF.

Risk factors for left atrial thrombus or spontaneous echo contrast in non-valvular atrial fibrillation patients with low CHA2DS2-VASc score.

OBJECTIVE: Risk factors of left atrial thrombus (LAT) or spontaneous echo contrast (LASEC) in non-valvular atrial fibrillation (NVAF) had been reported. However, information in the subgroup of NVAF patients with low CHA2DS2-VASc scores was limited. Here, we evaluated the risk factors of LAT/LASEC in NVAF patients with low CHA2DS2-VASc scores. METHODS: Transesophageal echocardiography (TEE) file of NVAF patients with low CHA2DS2-VASc scores was reviewed (between June 2009 and Feb 2019) in this retrospective observational study. Binary logistic regression analysis was performed to identify risk factors other than the CHA2DS2-VASc score. Propensity score matching (PSM) was used to further evaluate independent risk markers for LAT/LASEC. The newly discovered factors were added to the CHA2DS2-VASc score, and receiver operating characteristic analysis was used to evaluate the ability of the model to predict LAT/LASEC. RESULTS: TEE files of 3056 NVAF patients with low CHA2DS2-VASc scores were reviewed. Regression analysis revealed elevated fibrinogen and enlarged left atrium (LA) were risk factors for LAT/LASEC. Further PSM analysis confirmed that elevated fibrinogen and enlarged LA were independent risk factors for LAT/LASEC. After including fibrinogen and left atrial diameter (LAD), the CHA2DS2-VASc score was more accurate for LAT/LASEC prediction in NVAF patients with low CHA2DS2-VASc scores (area under the curve difference is 0.241, 95% confidence interval (CI) 0.188-0.294, Z = 8.890, P < 0.0001). CONCLUSIONS: Elevated fibrinogen and enlarged LA were independent risk factors for LAT/LASEC in NVAF patients with low CHA2DS2-VASc scores. Taking fibrinogen and LAD into consideration may help improve LAT/LASEC risk evaluation, which warrants further validation studies.

Differences in oral anticoagulant prescriptions between specialists and non-specialists in patients with cardioembolic stroke caused by non-valvular atrial fibrillation.

Atrial fibrillation (AF) is a common disease encountered in daily practice; however, few patients with AF received oral anticoagulant (OAC) therapy. This study focused on differences in OAC prescriptions and influencing factors between specialists (neurological and cardiovascular) and non-specialists. A retrospective comparative analysis was conducted on 480 patients with acute cardioembolic stroke caused by non-valvular AF who were admitted to our hospital between January 1, 2015, and December 31, 2020. All patients had visited our hospital or other hospitals for their underlying diseases. Overall, 232 (specialist group SG) and 248 patients (non-specialist group NSG) were examined by specialists and non-specialists, respectively. The NSG had a significantly lower percentage of OAC prescriptions on admission than the SG (P < 0.01), even after propensity score matching. Factors influencing OAC prescription in the SG were age, hypertension, paroxysmal AF, dementia, CHADS2 score, and antiplatelet drug use, while those in the NSG were a history of cerebral infarction, paroxysmal AF, dementia, and antiplatelet drug use [SG: age, odds ratio (OR) 0.919, 95% confidence interval (CI) 0.865-0.976; hypertension, OR 0.266, 95% CI 0.099-0.713; paroxysmal AF, OR 0.189, 95% CI 0.055-0.658; dementia, OR 0.253, 95% CI 0.085-0.758; CHADS2 score, OR 2.833, 95% CI 1.682-4.942; and antiplatelet drug use, OR 0.072, 95% CI 0.025-0.206; NSG: cerebral infarction, OR 5.940, 95% CI 1.581-22.309; paroxysmal AF, OR 0.077, 95% CI 0.010-0.623; dementia, OR 0.077, 95% CI 0.014-0.438; and antiplatelet drug use, OR 0.024, 95% CI 0.004-0.152]. In conclusion, the OAC prescription rate was higher in patients with non-valvular AF whose family physicians were specialists at the time of cerebral infarction onset. In addition, in the SG, advanced age and hypertension were associated with not prescribing OAC, whereas a higher CHADS2 score was associated with the prescription of OACs. In the NSG, a history of cerebral infarction was associated with the prescription of OACs. Further, paroxysmal AF, antiplatelet drug use, and dementia were associated with non-OAC therapy in both the groups.

Dabigatran plasma concentration indicated the risk of patients with non-valvular atrial fibrillation.

This study aimed to evaluate the variability of dabigatran plasma concentration and the association with clinical events in Chinese patients treated with dabigatran etexilate (DE) for non-valvular atrial fibrillation (NVAF). The steady-state concentration of dabigatran (the active metabolite of DE) was determined at trough and peak. The effect of dabigatran concentration variability and related factors on clinical outcomes were explored. Data from 86 patients receiving a fixed dose of 110 mg showed that dabigatran trough concentration varied remarkably. Age, BMI and history of heart failure were identified as important covariates for dabigatran trough concentration. Dabigatran trough concentration (P = 0.002) and history of hypertension (P = 0.012) scores were identified as key factors for predicting the risk of bleeding events. Dabigatran trough concentration, affected by Age, BMI and history of heart failure, may serve as an independent risk factor for bleeding events in Chinese patients treated with DE for NVAF.