Non-valvular Atrial Fibrillation Patients Research Articles

Abstract 14063: Eight Pharmacokinetic-Related Genetic Variants Were Not Associated With Bleeding From Direct Oral Anticoagulants in Non-Valvular Atrial Fibrillation Patients

Background. Atrial fibrillation (AF) is the leading cause of ischemic stroke and treatment has focused on reducing stroke risk through anticoagulation. Direct Oral Anticoagulants (DOACs) are the first-line guideline-recommended therapy in non-valvular AF since they are as effective and safer than warfarin. Although patients bleed less overall from DOACs, bleeding still is the main safety concern with this therapy. Previous studies have shown that genetic variants modify the function of metabolic enzymes or transporters involved in the pharmacokinetics (PK) of DOACs, which then affect DOAC plasma concentrations. However, whether those functional PK genetic variants are significantly associated with the risk of bleeding on DOACs is unknown. Aim. Assess the association of PK-related single nucleotide variants (SNVs) with the risk of bleeding from DOACs in non-valvular AF patients. Methods. A retrospective cohort study was carried out with 2,364 Caucasians with non-valvular AF and treated with rivaroxaban or apixaban. Patients were genotyped as part of the genomic biobank at the University of Michigan Health System. The primary endpoint was a composite of major and clinically relevant non-major (CRNM) bleeding. Cox proportional hazards regression with time-varying analysis assessed the association of 8 SNVs in 5 PK genes ( ABCB1 , ABCG2 , CYP3A4 , CYP3A5 , CYP2J2 ) with the risk of bleeding from DOACs in unadjusted and covariate-adjusted models. Six tests were performed as 3 of the SNVs are in the same haplotype. P-values below the Bonferroni-corrected level of 8.33e-3 were considered statistically significant. Results. A total of 412 (17.4%) major and CRNM bleeding events occurred over 2.27 ± 2.03 years of follow-up. None of the PK SNVs were significantly associated with bleeding risk on DOACs (Table 1). Conclusion. SNVs that affect the function of PK genes were not significantly associated with major and CRNM bleeding from rivaroxaban or apixaban in 2,364 AF patients.

Abstract 12102: Concomitance of Diabetes Mellitus and Prior Myocardial Infarction Associated With Poor Clinical Outcomes in Patients With Atrial Fibrillation: The Fushimi AF Registry

Background : Patients with diabetes mellitus (DM) have high risk of cardiovascular events such as cardiovascular death, stroke, heart failure and so on. Patients with history of myocardial infarction (MI) are also at high risk. The outcomes of patients with nonvalvular atrial fibrillation (NVAF) who have both DM and history of MI are unclear. Methods : From the Fushimi AF registry, we obtained NVAF patients who had both DM and history of MI (DM+MI+: N=107), either DM or history of MI (DM-MI+: N=156, and DM+MI-: (N=935), and neither DM nor history of MI (DM-MI-: N=3,197). Major adverse cardiovascular and cerebrovascular events (MACCE) and all-cause mortality were evaluated. MACCE was defined as composite events of cardiovascular death, myocardial infarction, stroke, and admission for heart failure. Results: The median follow-up period was 1,851 (interquartile range: 790-2,924) days. DM+MI+ patients were often male and had more heart failure, chronic renal disease, dyslipidemia, hypertension, and paroxysmal AF than other patients. DM+MI+patients had also higher risk scores (CHADS 2 , CHA 2 DS 2 -VASc and HAS-BLED scores). DM+MI+ patients had significantly higher incidence (% per patient-year) of MACCE and all-cause mortality than others (Figure A and B. MACCE: DM+MI+ 18.8%, DM-MI+ 8.0%, DM+MI- 6.1%, DM-/MI- 4.9%, log rank P<0.001, all-cause mortality: 10.2%, 6.1%, 5.2%, 4.5%, respectively, log rank P<0.001). In multivariate analysis, DM+MI+ was significantly associated with the incidence of MACCE compared with DM-/MI- (adjusted hazard ratio [95% confidence interval], 1.97 [1.36-2.87], P<0.001), although DM-MI+ and DM+MI had no association with it. In addition, DM+MI+ had no significant association with the incidence of all-cause mortality after multivariate adjustment. Conclusion: Patients with NVAF who have both DM and history of MI had more comorbidities and had significant association with adverse cardiovascular events.

Abstract 10015: Predictors of Primary Non-Adherence in Patients With Nonvalvular Atrial Fibrillation Prescribed Oral Anticoagulants in the US

Introduction: Primary non-adherence (PMN) is defined as the failure to fill an initial prescription for a medication or an appropriate alternative. This study assessed the rates and predictors of PMN among patients with non-valvular atrial fibrillation (NVAF) who were newly prescribed an oral anticoagulant (OAC). Methods: A retrospective database analysis of linked claims and electronic health record data was conducted using the Optum ® Market Clarity Dataset. Adult NVAF patients with a first written prescription for an OAC (apixaban, rivaroxaban, dabigatran, or warfarin) from 1/2016-6/2019 were identified (date of first prescription = index date). Patients had a 1-year pre-index period to describe baseline characteristics and a 6-month post-index period to assess rates of PMN, defined as having a written OAC prescription but not having a paid claim for any OAC within 30 days following the index date. Sensitivity analyses explored 60-, 90- and 180-day PMN thresholds. Logistic regression models were used to examine predictors of PMN. Results: The study sample comprised 20,393 patients (mean [SD] age 70.5 [11.3], 59.3% male, 90.0% Caucasian, 53.9% with Medicare only, 30.9% Commercial only, 54.5% in the Midwest). Apixaban (55.4%) was the most commonly prescribed OAC. The overall OAC 30-day PMN rate was 28.4%. Compared to warfarin, direct oral anticoagulants were associated with significantly higher odds of PMN (Figure 1). A CHA2DS2-VASc score of ≥3, Commercial insurance, and African American race were also associated with higher odds of PMN. Sensitivity analyses revealed decreasing PMN over time with a 180-day PMN rate of 17.0%. Conclusions: More than a quarter of patients experienced PMN within 30 days of an initial written OAC prescription; however, this rate decreases over a 180-day period, suggesting a delay in fills. Understanding the factors associated with no fills or delayed fills is warranted to guide interventions for improving OAC treatment rates in NVAF.

Comparison of primary and secondary stroke prevention in patients with nonvalvular atrial fibrillation: Results from the RAFFINE registry

ObjectivesClinical outcome data of primary and secondary prevention in patients with nonvalvular atrial fibrillation (NVAF) after the introduction of direct oral anticoagulant (DOAC) therapy are limited. Materials and MethodsA subgroup analysis of the RAFFINE registry, an observational, multicenter, prospective registry of Japanese patients with AF, was performed. Incidence rates of stroke or systemic embolism, all-cause death, major bleeding, and intracranial hemorrhage were compared between patients with and without a history of stroke or transient ischemic attack (TIA). ResultsOf 3,706 NVAF patients at baseline, 557 (15.0%) had a history of ischemic stroke or TIA (secondary prevention group), and 3,149 (85.0%) had no history of ischemic stroke or TIA (primary prevention group). The proportion of patients receiving oral anticoagulants was 87.2% (42.5% warfarin, 44.7% DOACs). The secondary prevention group had higher rates of stroke or systemic embolism (2.6% vs 1.0%/year, p<0.001), all-cause death (3.6% vs 2.4%/year, p<0.01), and major bleeding (2.0% vs 1.3%/year, p<0.01), and similar rates of intracranial hemorrhage (0.6% vs 0.5%/year, p=0.66) compared with the primary prevention group. A Cox proportional hazards model showed that a history of ischemic stroke or TIA was independently associated with an increased risk of stroke or systemic embolism (adjusted hazard ratio, 2.22; 95% confidence interval, 1.57 – 3.15; p<0.001). ConclusionsIn a contemporary cohort of NVAF patients, a history of ischemic stroke or TIA was still an independent predictor of stroke or systemic embolism, despite advances in anticoagulation therapy.

Left atrial strain for predicting recurrence in patients with non-valvular atrial fibrillation after catheter ablation: a single-center two-dimensional speckle tracking retrospective study

BackgroundAlthough catheter ablation (CA) is an effective treatment for non-valvular atrial fibrillation (AF), a good many of patients still have a recurrence following post-operation. Prediction of AF recurrence by evaluating left atrial (LA) phase function with speckle tracking echocardiography (STE) may be helpful for risk stratification and clinical management for AF patients. Therefore, the current study aimed to assess the prognostic value of LA strains in non-valvular AF patients after CA.MethodsA total of 95 non-valvular AF patients (70.5% paroxysmal AF, 56.8% males, mean age 63.2 ± 9.7 years) were included in this retrospective study between October 2019 and August 2020. Transthoracic echocardiography was performed in all the subjects and STE was used to analyze the LA reservoir strain (LASr), LA conduit strain (LAScd) and LA contractile strain (LASct) during different phases before CA. Patients were followed up with until January 2022. The endpoint was AF recurrence.ResultsOver a median follow-up period of 26.0 months (interquartile range, 24.7–26.7 months), 26 patients experienced recurrence and 69 stayed in sinus rhythm. Compared with no-recurrence group, maximum volume of LA (LAVmax), minimum volume of LA (LAVmin) and LA volume index (LAVI) were increased in the recurrence group, while LAEF, LASr and LASct were worsened (P < 0.05). Multivariable logistic regression analysis revealed that LASct was an independent predictor of AF recurrence (odds ratio, 0.89; 95% confidence interval (CI), 0.82–0.97; P = 0.007) and receiver operating characteristic (ROC) curve analysis showed an area under the curve of LASct<8% was 0.70 (95% CI, 0.59–0.79; P = 0.0008).ConclusionsLASct was of independent predictive value of AF recurrence. LA function assessed by STE may contribute to the risk stratification for AF patients and selection of suitable patients for CA.

Association between body mass index and long-term clinical outcomes in patients with non-valvular atrial fibrillation taking oral anticoagulants.

The association between body mass index (BMI) and clinical outcomes of patients with non-valvular atrial fibrillation (NVAF) taking oral anticoagulants (OACs) are controversial, and we thus analyzed the large registry data to elucidate them. We conducted a historical cohort study at 71 centers in Japan and included outpatients with NVAF taking vitamin K antagonists (VKAs). Physicians in charge could change VKAs to direct OACs based on their judgement during follow-up period. We categorized patients into four BMI groups (kg/m2): underweight (BMI < 18.5), normal weight (18.5 ≤ BMI < 25), overweight (25 ≤ BMI < 30), and obese (30 ≤ BMI). The effects of each BMI group relative to the normal weight group on clinical outcomes consisting of all-cause death, ischemic events, and bleeding events were estimated using Cox proportional hazard models adjusting for potential confounders. We also constructed restricted cubic spline regression model adjusted by multivariable Cox proportional hazard models. We included 6927 patients consisting of an underweight (n = 386), normal weight (n = 3785), overweight (n = 2174), and obese (n = 582) groups. The median follow-up period was 3.9years. In the underweight group, the adjusted hazard ratios (HRs) for all-cause death and ischemic events were 1.75 (1.30-2.34) and 1.61 (1.04-2.50). The HR for all-cause death was 0.63 (0.49-0.82) in the overweight group. Restricted cubic spline regression models confirmed that lower BMI showed significantly higher risks for all-cause death and ischemic events. Among NVAF patients taking OACs, underweight patients had higher risks of all-cause death and ischemic events than other patients. Overweight patients had lower risk of all-cause death.

Correlation Between Serum Albumin and D-Dimer Levels in 909 Patients with Non-Valvular Atrial Fibrillation: A Retrospective Study from a Single Center in China.

BACKGROUND D-dimer level can reflect the hypercoagulable state of atrial fibrillation (AF) and predict thromboembolic events. However, no effective indicator associated with D-dimer of AF patients has been found to prevent thromboembolic events in AF. This retrospective study from a single center aimed to investigate the correlation between serum albumin and D-dimer levels in 909 patients with non-valvular AF (NVAF) and 653 subjects in sinus rhythm. MATERIAL AND METHODS A total of 909 NVAF patients and 653 sex- and age-matched sinus rhythm participants were used to compare serum albumin and D-dimer levels. Serum albumin was determined by colorimetry, and D-dimer level was determined by latex-enhanced photoimmunoassay. We analyzed the correlation of serum albumin and D-dimer with NVAF by correlation analysis, logistic regression analysis, and receiver operating characteristic (ROC) curve. RESULTS Albumin (P<0.001) and D-dimer (P<0.001) were significantly associated with NVAF. Among NVAF patients, D-dimer level was negatively correlated with albumin levels (P<0.001), and albumin level was an independent risk factor of abnormal D-dimer level (>0.5 ug/mL), which was also an effective predictor of abnormal D-dimer level (the area under the ROC curve was 0.77, P<0.001), and the optimal cutoff value was 36.95 g/L. CONCLUSIONS Serum albumin and D-dimer levels were significantly associated with NVAF. In NVAF patients, D-dimer level was inversely correlated with albumin levels, and albumin level was an independent risk factor and effective predictor of abnormal D-dimer level. Close examination and supplementation of serum albumin can prevent thromboembolic events, but further clinical research and confirmation are needed.

Predictors of dementia amongst newly diagnosed non-valvular atrial fibrillation patients

Atrial fibrillation (AF) confers a 2-to-3-fold increased risk of developing cognitive dysfunction and dementia, independent of age and past stroke. The purpose of study was to identify risk factors for developing dementia amongst AF patients in India. This was a single-centre, prospective, observational study wherein recently diagnosed, treatment naïve, persistent non-valvular AF patients were enrolled. All patients were screened for dementia using the Mini-Mental state exam. Amongst a total of 108 patients enrolled, 40 (37%) had dementia. The most common cognitive deficits were in attention and calculation followed by memory deficits. Factors independently contributing to dementia were advanced age, female sex, presence of diabetes, elevated pulmonary artery pressures and a lower serum albumin.

Oral Anticoagulants in Very Elderly Nonvalvular Atrial Fibrillation PatientsWith High Bleeding Risks: ANAFIE Registry.

Data on the effectiveness and safety of oral anticoagulant (OAC) agents in very elderly nonvalvular atrial fibrillation patients with high bleeding risk are lacking. This study examined 2-year outcomes and effects of OAC agents among these patients using the ANAFIE (All Nippon Atrial Fibrillation in the Elderly) registry (N=32,275) data. Patients were classified into high-risk (age:≥80 years; CHADS2 score:≥2; and presence of≥1 bleeding risk factor: creatinine clearance of 15-30mL/minute, prior bleeding at critical sites, body weight of≤45kg, or continuous antiplatelet use) and reference groups. In the high-risk (n=7,104) and reference (n=25,171) group patients, 89.0% and 93.4%, respectively, used OAC agents. Of these, respectively, 30.1% and 24.2% used warfarin, and 58.9% and 69.1% used direct-acting OAC (DOAC) agents. Compared with the reference group, the high-risk group had higher incidences of stroke/systemic embolism, major bleeding, intracranial hemorrhage, gastrointestinal bleeding, cardiovascular events, and all-cause death. In the high-risk group, DOAC agent use vs nonuse of OAC agents was associated with reduced incidences of stroke/systemic embolism (HR: 0.53; 95%CI: 0.36-0.79) and all-cause death (HR: 0.65; 95%CI: 0.52-0.81) but not with major bleeding (HR: 1.09; 95%CI: 0.63-1.89). DOAC agents were superior to warfarin in effectiveness and safety. For high-risk patients, history of major bleeding, severe liver dysfunction, and falls within 1 year were independent risk factors for major bleeding. High-risk elderly nonvalvular atrial fibrillation patients had higher event incidences. DOAC agents were associated with reduced risk of stroke/systemic embolism and all-cause death vs nonuse of OAC agents or warfarin. (Prospective Observational Study in Late-Stage Elderly Patients With Nonvalvular Atrial Fibrillation [ANAFIE registry]; UMIN000024006).

Dementia amongst newly diagnosed non-valvular atrial fibrillation patients in India: Prevalence and its predictors

Dementia amongst newly diagnosed non-valvular atrial fibrillation patients in India: Prevalence and its predictors

Performing transcatheter left atrial appendage closure: Techniques and challenges.

The left atrial appendage (LAA) has been demonstrated to be the major source of thromboemboli in patients with atrial fibrillation.1 The rationale of LAA closure is based on eliminating LAA continuity with the left atrium (LA), thereby reducing stroke risk. Indeed, left atrial appendage occlusion (LAAO) procedures play an important role in anticoagulation-intolerant patients who are at risk for atrial fibrillation–related stroke. Based on the PROTECT AF (Watchman Left Atrial Appendage System for Embolic PROTECTion in Patients With Atrial Fibrillation)2 and PREVAIL (Prospective Randomized Evaluation of the WATCHMAN LAA Closure Device in Patients With Atrial Fibrillation [AF] Versus Long Term Warfarin Therapy)3 studies, the Food and Drug Administration (FDA) approved use of the Watchman (Boston Scientific, Marlborough, MA) device in 2015, with an updated generation of device subsequently ratified in 2020 following the PINNACLE-FLX (Protection Against Embolism for Nonvalvular AF Patients: Investigational Device Evaluation of the Watchman FLX LAA Closure Technology) study.

Population pharmacokinetic analysis for dabigatran etexilate in Chinese patients with non-valvular atrial fibrillation.

We aimed to develop a pharmacokinetic (PK) and pharmacodynamic (PD) model from healthy Chinese subjects and real-world non-valvular atrial fibrillation (NVAF) patients. We also investigated meaningful intrinsic and extrinsic factors and related biomarkers for bleeding events. We characterized the integrated PK/PD models based on rich PK/PD data [dabigatran concentration, activated partial thromboplastin time (APTT), prothrombin time (PT), and anti-factor IIa (anti-FIIa) activity] from 118 healthy volunteers and sparse PD data [APTT, PT, and anti-FIIa] from 167 patients with NVAF after verifying the model extrapolation performance. We also documented the correlations between PD biomarkers and clinically relevant bleeding events over one year. Next, we used the final integrated PK/PD model (a two-compartment, linear model with first-order absorption) to evaluate the influence of dosage and individual covariates on PD parameters. The age, high-density liptein cholesterol (HDL-C), and creatinine clearance (CrCL) improved the PK model fit. The linear direct-effects PD model described the correlation between APTT, PT, and anti-FIIa and plasma concentration. CrCL improved the PD model fit. Anti-FIIa was more sensitive to the increase in dabigatran exposure than APTT and PT in the PD model. Therefore, fixed dabigatran doses could be prescribed for patients with NVAF without adjusting for age and HDL-C. We observed an elevated bleeding tendency with higher peak and trough values of APTT, PT, and anti-FIIa. Randomized studies should be performed to evaluate the efficacy and safety of low-dose dabigatran in Chinese patients with NVAF.

Does types of atrial fibrillation matter in the impairment of global and regional left ventricular mechanics and intra-ventricular dyssynchrony?

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia, which is associated with cardiac dysfunction. This study aimed to compare the impairment severity of left ventricular strain and intra-ventricular dyssynchrony using echocardiography-derived velocity vector imaging in patients with different types of AF without heart failure. 168 non-valvular AF patients with normal left ventricular ejection fraction (98 paroxysmal AF patients and 70 persistent AF patients) and 86 healthy control subjects were included in this study. Regional and global left ventricular longitudinal and circumferential strain were measured. Time to regional peak longitudinal strain was measured and the standard deviation of all 12 segments (SDT-S) was used as a measure of intra-ventricular dyssynchrony. Significantly lower GLS (-18.71 ± 3.00% in controls vs. -17.10 ± 3.01% in paroxysmal AF vs. -12.23 ± 3.25% in persistent AF, P < 0.05) and GCS (-28.75 ± 6.34% in controls vs. -24.43 ± 6.86% in paroxysmal AF vs. -18.46 ± 6.42% in persistent AF, P < 0.01) were observed in either persistent AF subjects or paroxysmal AF subjects compared with healthy control subjects (P < 0.05). The impairment was much worse in persistent AF subjects compared with paroxysmal AF subjects (P < 0.001). Intraventricular dyssynchrony was found in both persistent AF patients and paroxysmal AF patients, and it's worse in persistent AF patients (52 ± 18 ms in controls, 61 ± 17 ms in paroxysmal AF, and 70 ± 28 ms in persistent AF, P < 0.05). Multivariate regression analysis revealed AF types were independent risk factors of GLS, GCS, and intraventricular dyssynchrony. AF types were not only associated with impaired longitudinal and circumferential left ventricle mechanics but also intra-ventricular mechanical dyssynchrony. Worse systolic mechanics and intra-ventricular dyssynchrony were found in patients with persistent AF compared with these in patients with paroxysmal AF.

Characterization of baseline clinical factors associated with incident worsening kidney function in patients with non-valvular atrial fibrillation: the Hokuriku-Plus AF Registry.

Evidence suggests that atrial fibrillation (AF) could increase the risk of worsening kidney function (WKF) which is linked to an increased risk of stroke, bleeding, and death in AF patients. However, limited data exist regarding the factors that could lead to WKF in these patients. Therefore, we sought to identify the potential factors associated with the development of WKF in patients with non-valvular AF (NVAF). We analyzed prospectively recruited 1122 NVAF patients [men 71.9%, median age 73.0years (interquartile range: 66.0-79.0)] with a baseline estimated glomerular filtration rate (eGFR) ≥ 15mL/min/1.73 m2 from the Hokuriku-Plus AF Registry. The primary outcome was incident WKF, defined as the %eGFR change from the baseline ≥ 30% during the follow-up period. We evaluated the association between baseline variables and incident WKF using univariate and multivariate Cox proportional hazard models. We also evaluated the non-linear association between the identified factors and incident WKF. During a median follow-up period of 3.0years (interquartile range: 2.7-3.3), incident WKF was observed in 108 patients (32.6 per 1000 person-years). Compared to the patients without incident WKF, the patients with incident WKF were older and had a higher prevalence of heart failure (HF), diabetes mellitus (DM), and vascular disease at baseline. Those who experienced incident WKF also had higher diastolic blood pressure, lower hemoglobin, lower eGFR, higher B-type natriuretic peptide (BNP) and used warfarin more frequently. Upon multivariate analysis, age ≥ 75years, HF, DM, and anemia were independently associated with incident WKF. Additionally, age and hemoglobin were linearly associated with the risk of incident WKF, whereas a J- or U-shaped association was observed for HbA1c and BNP. Age ≥ 75years, HF, DM, and anemia were associated with the development of WKF in Japanese patients with NVAF. In patients with these risk factors, a careful monitoring of the kidney function and appropriate interventions may be important when possible.

Oral anticoagulation use in non-valvular atrial fibrillation patients in rural setting

BackgroundThe 2019 ACC/AHA/HRS guidelines established direct oral anticoagulants (DOACs) as first line therapy over warfarin for non-valvular atrial fibrillation (AF). MethodsAmbulatory clinic patients with non-valvular AF or atrial flutter seen between 10/1/2019-7/12/2020 included. High-risk AF defined as males CHA2DS2-VASc score ≥2 and females ≥3. Patients were separated into: warfarin, DOAC, or no oral anticoagulation (OAC). ATRIA bleed score calculated. A provider survey assessing knowledge and barriers to anticoagulation completed via REDCap between 3/5-4/16/2020. ResultsOf 12,014 subjects with AF, 8,032 were high risk (mean age 75.9 ± 9.8 years; 57.5% male). There were 4,619 (57.1%) ≥ 75 years and 63.4% were rural dwelling. There was no significant difference between the number of subjects on anticoagulation before and after the guideline publication (75.6% vs. 75.7%, p = 0.79). Warfarin use decreased 2.3% over 1 year (39.3% to 37.0%), while DOACs increased 2.4% (36.2% to 38.7%, p < 0.001 for both). At 1-year, age, male gender, CHA2DS2-VASc score 4-6, hypertension, stroke and cardiology consult increased prescription of OAC (p<0.05). Vascular disease, high risk ATRIA bleed, renal disease, prior hemorrhage, and left atrial appendage occlusion were associated with decreased OAC use (p < 0.05). Left atrial appendage occlusion device use was low (<1%). In a survey, majority of providers noted bleeding risk (35.1%) and cost (25.0%) to be the biggest barriers to DOAC use. ConclusionsThe new guidelines caused a slight increase in DOACs over time. Significant barriers to DOAC use exist in rural areas; one in four high risk AF patient remains without OAC therapy.

Safety of Apixaban Monotherapy for Non-Valvular Atrial Fibrillation-Related Acute Stroke with Intra-/Extracranial Artery Stenosis

Introduction: We investigated whether apixaban is safe for the prevention of further adverse events in non-valvular atrial fibrillation (NVAF) patients with intra-/extracranial artery stenosis (Stenosis group) compared with acute large vessel occlusion without intra-/extracranial artery stenosis (No stenosis group). We also examined whether combination therapy using apixaban and antiplatelet is safe. Methods: ALVO (Apixaban on clinical outcome of patients with Large Vessel Occlusion [LVO] or stenosis) was a historical and prospective multicenter registry at 38 centers in Japan. Patients with NVAF and acute LVO or stenosis who received apixaban within 14 days after onset were included. We conducted the post hoc analysis using the ALVO dataset. We compared patients with stenosis versus those without stenosis in terms of the primary outcome, which was defined as a composite of all-cause death, major bleeding events, and ischemic events 365 days after onset. Results: Of the 662 patients, 54 (8.2%) patients were classified into the Stenosis group, and 104 patients of the total (16%) reached the primary outcome. The cumulative incidence of primary outcome was not significantly different between the No stenosis and the Stenosis groups (hazard ratio [HR] 1.2, 95% confidence interval [CI]: 0.64–2.4; p = 0.52). Even after adjustment for predictive clinical variates, no significant difference in the primary endpoint between the No stenosis and the Stenosis groups was shown (adjusted HR 1.2, 95% CI: 0.59–2.5; p = 0.60). Fifty patients (7.6%) used an antiplatelet with apixaban. Among the Stenosis group patients, the cumulative incidence of the primary outcome was significantly higher among patients treated with an antiplatelet and apixaban (HR 3.5, 95% CI: 1.0–12; p = 0.048). Conclusion: Apixaban monotherapy appears safe for the prevention of further adverse events in the Stenosis group patients similar to the No stenosis group patients. Concomitant use of an antiplatelet might not be favorable in patients with stenosis.

N-terminal pro-B-type natriuretic peptide and D-dimer combined with left atrial diameter to predict the risk of ischemic stroke in nonvalvular atrial fibrillation.

We aimed to explore the potential role of N-terminal pro-B-type natriuretic peptide (NT-proBNP), d-dimer, and the echocardiographic parameter left atrial diameter (LAD) in identifying and predicting the occurrence of ischemic stroke (IS) in patients with nonvalvular atrial fibrillation (NVAF). We conducted a retrospective study of 445 patients with NVAF in the First Affiliated Hospital of Nanchang University. They were divided into the NVAF (309 cases) and NVAF with stroke (136 cases) groups according to whether acute ischemic stroke (AIS) occurred at admission. Multivariate logistic regression was used to analyze the odds ratio (OR) of NT-proBNP, d-dimer, and LAD for IS. The predictive value of NT-proBNP, d-dimer, and LAD in identifying the occurrence of IS in NVAF was determined by plotting the receiver operating characteristic (ROC) curves. NT-proBNP, d-dimer, and LAD levels were significantly higher in the NVAF with stroke group than in the NVAF group (p < .05). NT-ProBNP, d-dimer, and LAD were independently associated with IS in NVAF patients (odds ratio [OR] = 1.12, 95% confidence interval [CI]: 1.08-1.16; OR = 1.87, 95% CI: 1.37-2.55; OR = 1.21, 95% CI: 1.13-1.28, p < .01). The optimal cutoff points for NT-ProBNP, d-dimer, and LAD levels to distinguish the NVAF group from the NVAF with stroke group were 715.0 pg/ml, 0.515 ng/ml, and 38.5 mm, respectively, with the area under the curve (AUC) being [0.801 (95% CI: 0.76-0.84); 0.770 (95% CI: 0.72-0.85); 0.752 (95% CI: 0.71-0.80), p < .01]. The combined score of NT-proBNP, d-dimer, and LAD improved the predictive efficacy of the single index, with an AUC of 0.846 (95% CI: 0.81-0.88, p < .01), sensitivity of 77.2%, and specificity of 76.4%. NT-proBNP, d-dimer, and the echocardiographic parameter LAD have outstanding value in predicting the risk of IS in patients with NVAF.

A descriptive cross-sectional study of self-management in patients with nonvalvular atrial fibrillation.

Self-management of non-valvular atrial fibrillation (NVAF) is characterized by complexity and diversity of content. Inadequate self-management exposes patients to the risk for complications such as stroke and bleeding. To assess the status and predictors of self-management in NVAF patients, a descriptive cross-sectional study was conducted. The self-management scales for atrial fibrillation were used to assess the status of self-management of patients who received Warfarin, NOAC, Aspirin, or No anticoagulant therapy. The general situation questionnaire was used to collect socio-demographic and clinical data from patients. A total of 555 participants completed the survey, with self-management score of 71.21 ± 12.33, 69.59 ± 13.37, 69.03 ± 12.20 and 66.12 ± 11.36 in Warfarin group, NOAC group, Aspirin group and No anticoagulant group, respectively. In Warfarin group lower educational status was associated with poor self-management; in Aspirin group, comorbidities and age < 65 years (P = .001) were associated with poor self-management; in No anticoagulant group, age < 65 years, single, poor sleep quality, and permanent AF were associated with poor self-management. Self-management was inadequate in patients with NVAF. Poor self-management might be related with the occurrence of cerebral embolism. For NVAF patients receiving anti-thrombotic therapy, relatively young age, comorbidities, and age can have a substantial impact on self-management performance; while age, type of AF, quality of sleep, married status are associated with self-management in patients with no anticoagulants.

Effect of congestive heart failure on safety and efficacy of left atrial appendage closure in patients with non-valvular atrial fibrillation

ABSTRACT Objectives To evaluate the influence of congestive heart failure (CHF) on safety and efficacy of left atrial appendage closure (LAAC) in non-valvular atrial fibrillation (NVAF) patients. Methods A total of 401 patients who consecutively underwent LAAC with Watchman and LAmbre devices were divided into CHF (85 cases) and non-CHF (316 cases) groups. Comparisons between groups were performed against data. Results No significant differences were found in implantation success and periprocedural complication rates between the two groups. During a mean 2.2 years of follow-up, the incidence rate of thromboembolism, major bleeding, device-related thrombus, and non-cardiovascular death was comparable. However, patients with CHF had significantly increased risk of all-cause death (P = 0.015), cardiovascular death (P = 0.014), and combined efficacy endpoints (P = 0.02). After performing propensity score matching, the risk of all-cause death (P = 0.01), cardiovascular death (P = 0.01), and combined efficacy endpoints (P = 0.006) was still higher. The logistic regression analyses identified CHF (OR: 3.642, 95% CI: 1.296–10.232, P = 0.014) as an independent predictor of cardiovascular death. Conclusions Implantation of atrial appendage occluder is effective and safe in NVAF patients with CHF. The increased risk of mortality and combined efficacy endpoints in patients with CHF versus non-CHF after LAAC may be associated with the high risk of CHF itself.

Usefulness of echocardiographic parameters in predicting the incidence of ischemic stroke in Japanese patients with non-valvular atrial fibrillation

Abstract Background Atrial fibrillation (AF) is a risk factor for ischemic stroke (IS). We developed a novel risk score of IS (HELT-E2S2 score) in non-valvular atrial fibrillation (NVAF) patients from the combined database of 5 major AF registries in Japan. However, this score does not include echocardiographic (Echo) parameters that have been reported to be risk factors of IS, such as left atrial diameter (LAD) enlargement or increased relative wall thickness (RWT) of left ventricle (LV). Purpose To investigate the predictive value of Echo parameters in Japanese patients with NVAF. Methods After excluding patients without the Echo data, 6,032 NVAF patients were analyzed in the present study. LAD was measured in the parasternal long axis view at the end-ventricular systole. RWT was calculated as (2x posterior wall thickness)/ LV end-diastolic dimension. We compared clinical characteristics and the incidence of IS between NVAF patients divided by LAD level (High/Low LAD group) and RWT level (High/Low RWT group). To balance the follow-up period among the registries, event data from individuals whose follow-up period exceeded 730 days were excluded from the analysis. Results The optimal cut-off value of LAD and RWT to predict the incidence of IS with the receiver operating characteristic analysis was 43.3 mm and 0.4167, respectively. Between the High/Low LAD groups (High LAD: n=2,640 vs. Low LAD: n=3,392), age (70.3±12.1 vs. 68.3±12.5 years; p&amp;lt;0.001), CHA2DS2-VASc score (3.02±1.84 vs. 2.57±1.78; p&amp;lt;0.001), HELT-E2S2 score (2.20±1.31 vs. 1.55±1.33; p&amp;lt;0.001), the prescription of oral anticoagulants (OACs) (69.5 vs. 51.5%; p&amp;lt;0.001), LV ejection fraction (60.4±13.4 vs. 64.4±10.7%; p&amp;lt;0.001) and RWT (0.401±0.091 vs. 0.396±0.082; p=0.02) were significantly different. Between the High/Low RWT groups (High RWT: n=2,293 vs. Low RWT: n=3,739), percentage of female (35.6 vs. 27.8%; p&amp;lt;0.001), age (71.2±12.1 vs. 68.0±12.4 years; p&amp;lt;0.001), CHA2DS2-VASc score (3.08±1.82 vs. 2.58±1.79; p&amp;lt;0.001), HELT-E2S2 score (2.10±1.39 vs. 1.67±1.31; p&amp;lt;0.001), the prescription of OACs (62.6 vs. 57.4%; p&amp;lt;0.001), LV ejection fraction (65.5±9.9 vs. 60.9±13.0%; p&amp;lt;0.001) and LAD (43.0±8.1 vs. 42.4±8.3; p=0.004) were significantly different. In Kaplan-Meier analysis, the incidence of IS was different between the groups during the median follow-up period of 730 days (High LAD vs. Low LAD; 1.82 vs. 1.00 per 100 person-years; p&amp;lt;0.001, by log-rank test, High RWT vs. Low RWT; 1.86 vs. 1.06; p&amp;lt;0.001) (Figure). Both High LAD (hazard ratio: 1.65, 95% CI: 1.12–2.46; p=0.01) and High RWT (hazard ratio: 1.43, 95% CI: 1.01–2.04; p=0.045) were independent predictors of the incidence of IS after adjustment by the components of the HELT-E2S2 score and other clinically relevant variables including co-existing diseases, gender, and the prescription of OACs (Table). Conclusion Echo parameters, LAD and RWT, were independently associated with the incidence of IS among Japanese patients with NVAF. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Japan Agency for Medical Research and Development