Non-valvular Atrial Fibrillation Risk Research Articles

Left Atrial Appendage Occlusion as a Strategy for Reducing Stroke Risk in Nonvalvular Atrial Fibrillation.

Nonvalvular atrial fibrillation (AF) is a common rhythm disorder of middle-aged to older adults that can cause ischemic strokes and systemic embolism. Stroke prevention is a crucial aspect of management, considering the increasing AF population and the associated morbidity and mortality. The left atrial appendage (LAA) has been identified as a predominant source of AF-associated thrombus and stroke, with at least 90% of the thrombi originating from this anatomical structure. Lifelong use of oral anticoagulants reduces the risk of these ischemic events but increases the risk of major and clinically relevant hemorrhages. In addition, these medications also require strict compliance for efficacy and have high failure rates in higher-risk patients. LAA occlusion (LAAO) has emerged as an alternative strategy for stroke prevention with encompassing various percutaneous and surgical techniques. Randomized controlled trials evaluating this intervention have shown promising results in stroke reduction replacing anticoagulation therapy. In this review, we aim to provide a comprehensive overview on the anatomy of the LAA and its role in thrombus formation, the emergence of various LAAO techniques and devices, and provide evidence on the role of LAAO in the reduction of stroke risk among patients with nonvalvular AF.

Interatrial block and abnormal P-wave electrocardiographic parameters as non-invasive predictors of atrial fibrillation

Aim. To identify noninvasive markers of atrial electrical dysfunction and risk of nonvalvular atrial fibrillation (AF) and to develop a predictive mathematical model to estimate the AF risk based on electrocardiographic (ECG) P-wave parameters during sinus rhythm.Methods. The study included 211 patients with cardiovascular pathology (aged median 62 [52; 71] years, 67.8% male, NYHA heart failure class I-III). All patients (follow-up median 45 [26; 67] months) underwent a complex of studies: 12-lead ECG, echocardiography, 24-hour ECG monitoring. Based on surface ECG data during sinus rhythm, parameters of atrial electrical activation were assessed such as Morphology, Voltage and P waves duration (MVP) according to integral analysis by MVP score.Results. During 3.7-year period, 44 (20.8%) patients experienced new-onset sustained AF and 12 (5.69%) patients developed ischemic stroke. As a result of ROC analysis and univariate Cox regression, independent predictors of AF were identified: P-wave prolongation in the DII lead, 3rd degree or advanced interatrial block (aIAB), an increase P-wave terminal force in lead V1 (PTFV1), low-voltage P-wave in the DI lead and сalculated level of abnormal P-wave ≥3 points on the MVP score. Data from multivariate Cox proportional hazards regression analysis confirmed the prognostic significance for three independent predictors of AF: aIAB (hazard ratio (HR) 5.92; 95% confidence interval (CI) [2.48-4.12]; p=0.0001); PTFV1 (HR 1.14; 95% CI [1.04-1.24], p=0.003); low-voltage P-wave in lead DI <0.1 mV (HR 1.03; 95% CI [1.02-1.05]; p=0.0001); and as a result a mathematical model was created to predict AF risk (-2LL =258; χ2=105; p=0.0001). Predictors such as PTFV1 (HR 1.41; 95% CI [1.17-1.72], p=0.0001) and MVP score of abnormal P-waves (HR 1.85; 95% CI [1.27-1.72] 2.70], p=0.001) were associated with a high risk of stroke according to Cox regression model (-2LL= 62.5; χ2=38.4; p <0.001).Conclusion. Complex of ECG markers of atrial electrical dysfunction such as aIAB, PTFV1, level MVP score of abnormal P-wave and low P-wave voltage allows identifying patients at high risk of AF and ischemic stroke.

Effectiveness and Safety of Edoxaban Compared With Apixaban in Elderly Patients With Nonvalvular Atrial Fibrillation: A Real-World Population-Based Cohort Study.

The very elderly (≥80 years) are at high risk of nonvalvular atrial fibrillation and thromboembolism. Given its recent approval, the comparative effectiveness and safety of edoxaban in this population, relative to the commonly used apixaban, remain unknown. Using the United Kingdom Clinical Practice Research Datalink, we identified a cohort of patients aged ≥80 with incident nonvalvular atrial fibrillation and newly treated with edoxaban or apixaban between 2015 and 2021. Cohort entry was defined as the first prescription for one of the 2 drugs. We used propensity score fine stratification and weighting for confounding adjustment. A weighted Cox proportional hazards model was used to estimate the hazard ratios (HR) with 95% CI of ischemic stroke/transient ischemic attack/systemic embolism (primary effectiveness outcome) and of major bleeding (primary safety outcome) associated with edoxaban compared with apixaban. We also assessed the risk of all-cause mortality and a composite outcome of ischemic stroke/transient ischemic attack, systemic embolism, gastrointestinal bleeding, and intracranial hemorrhage as secondary outcomes. The cohort included 7251 new-users of edoxaban and 39 991 of apixaban. Edoxaban and apixaban had similar incidence rates of thromboembolism (adjusted rates, 20.38 versus 19.22 per 1000 person-years; adjusted HR, 1.06 [95% CI, 0.89-1.26]), although the rates of major bleeding were higher with edoxaban (adjusted rates, 45.57 versus 31.21 per 1000 person-years; adjusted HR, 1.42 [95% CI, 1.26-1.61]). The risk of the composite outcome was 21% higher with edoxaban (adjusted HR, 1.21 [95% CI, 1.07-1.38]). All-cause mortality was similar between edoxaban and apixaban (adjusted HR, 1.04 [95% CI, 0.96-1.12]). In very elderly patients with nonvalvular atrial fibrillation, edoxaban resulted in similar thromboembolism prevention as apixaban, although it was associated with a higher risk of major bleeding. These findings may improve the management of nonvalvular atrial fibrillation by informing physicians on the choice of anticoagulant for this vulnerable population.

Abstract TMP76: Left Atrial Appendage Closure In Atrial Fibrillation Patients At High Intracranial Hemorrhage Risk

Background: Lifelong oral anticoagulant (OAC) use is associated with higher intracranial hemorrhage (ICH) risk in nonvalvular atrial fibrillation (NVAF) patients. We aimed to assess the long-term outcomes of left atrial appendage closure (LAAC) in NVAF patients at high baseline ICH risk, as LAAC was FDA-approved for NVAF patients who have a reasonable rationale to seek a nonpharmacological alternative to lifelong OAC use. Methods: We collected baseline and follow up data from consecutive NVAF patients who had LAAC because of either past ICH or finding cerebral microbleeds (CMB) on MRI without ICH (CMB-only). The outcome measures were the occurrence of ICH or acute ischemic stroke (AIS) after LAAC. Results: Out of a total of 644 LAAC performed in a single hospital system between 2015-2022, 142 NVAF patients had LAAC with WATCHMAN because of past ICH or CMB-only. Their mean age was 75.8± 7.6, 41 were female (29%). Mean CHA 2 DS 2 -VASc score was 5.24±1.4. Of the 142 patients, 67 (47.2%) had intraparenchymal hemorrhage (IPH, 52% related to cerebral amyloid angiopathy [CAA]), 19 (13.4%) had non-traumatic subdural hemorrhage (SDH), 36 (25.3%) had traumatic ICH (T-ICH), and 20 (14.08%) were CMB-only (65% with CAA pattern). Eighty-one patients were discharged on OAC (57%) and 133 patients were not taking OAC at 1 year (94%). Over a mean 1.98 years follow up, one patient had recurrent non-traumatic IPH (incidence rate [IR] 0.36 per 100 patient-years), four had traumatic ICH/SDH due to severe falls (IR 1.4%/year), and five had AIS (IR 1.78%/year). Conclusions: In NVAF patients at high ICH risk, our results show a 74% decrease in AIS risk (actual 1.76%/year vs expected 6.8%/year based on CHA 2 DS 2 -VASc). Despite the very high ICH risk population studied including at least 48 CAA patients, only one patient had a recurrent IPH after LAAC. LAAC should be considered in NVAF patients at high ICH risk and studied in RCTs in this cohort.

Severe Left Atrial Spontaneous Echo Contrast in Nonvalvular Atrial Fibrillation: Clinical Characteristics and Impact on Ischemic Risk Postablation.

Spontaneous echo contrast (SEC) is an important precursor for intracardiac thrombus and stroke. There are very limited data on characteristics of severe SEC and its impact on ischemic risk of nonvalvular atrial fibrillation (NVAF) patients after radiofrequency catheter ablation. Transesophageal echocardiography files were reviewed between March 2009 and March 2021 in this monocentric retrospective study. SEC was classified into four levels. The primary endpoint was thromboembolic event (stroke, myocardial infarction, systemic embolism, and ensuing death), and the secondary endpoint included nonischemic mortality and recurrent atrial arrhythmia. Six hundred SEC cases were enrolled and classified into mild SEC group (Grade 1-2, n = 515) and severe SEC group (Grade 3-4, n = 85). Independent risk factors for severe SEC included higher brain natriuretic peptide (BNP), erythrocyte sedimentation rate (ESR), and LAd/∆LVED (LAd = left atrial diameter; ∆LVED = left ventricular end-diastolic diameter - left ventricular end-systolic diameter). The severe SEC group had a higher peri-procedural ischemic event occurrence (7.1 vs. 1.9%, p = 0.007). At a median follow-up of 55 months, the severe SEC group had a lower freedom rate from ischemic events (90.1 vs. 75.3%, p < 0.001); older age and severe SEC were independent risk factors for ischemic events. In patients undergoing redo-procedure (n = 100), a remarkably reduced ESR (17.8 ± 12.0 vs. 28.2 ± 19.0 mm/h, p < 0.001) was observed in patients whose SEC disappeared. Higher BNP, ESR, and LAd/∆LVED were the independent predictors for severe SEC. Severe SEC was associated with higher peri-procedural and long-term ischemic risks. ESR and LAd/∆LVED, as indicators of hematological and hemodynamic change, seemed helpful in identifying NVAF patients prone to developing severe SEC.

Delaying clinical events among patients with non-valvular atrial fibrillation treated with oral anticoagulants: Insights from the ARISTOPHANES study

BackgroundOral anticoagulants (OACs) mitigate stroke and systemic embolism (SE) risk in non-valvular atrial fibrillation (AF) patients but can increase the risk of major bleeding (MB). This study analyzed the gains in event-free time for these outcomes among OAC treatment options represented in the ARISTOPHANES study. MethodsThis sub-analysis consisted of NVAF patients who initiated warfarin, apixaban, dabigatran, or rivaroxaban from 01JAN2013-30SEP2015, with data pooled from Medicare and 4 US commercial claims databases. Propensity score matching was conducted between non-vitamin K antagonist OAC (NOAC) and warfarin cohorts in each database and results were pooled. Laplace regression was used to evaluate the delay in time to stroke/SE and MB events between NOACs and warfarin and between NOACs after the first 12-months of follow-up. ResultsThe population included 466,991 patients (167,413 warfarin; 108,852 apixaban; 37,724 dabigatran; and 153,002 rivaroxaban). Event-free time gain (95% confidence interval) for apixaban versus warfarin was 101 days (78- 124) for stroke/SE and 116 (103- 130) days for MB. The gain in event-free time for dabigatran versus warfarin was 45 days (3- 87) for stroke/SE and 92 (68- 116) days for MB. The gain in event-free time for rivaroxaban versus warfarin was 63 days (42- 84) for stroke/SE but event-free time decreased by 18 (-31–6) days for MB. ConclusionsOver 12 months after initiation, apixaban and dabigatran conferred progressive increases in event free time for stroke/SE and MB vs warfarin, whereas rivaroxaban conferred an increase in stroke/SE-free time but a loss in MB-free time vs warfarin.

Anticoagulation Holiday: Resumption of Direct Oral Anticoagulants for Atrial Fibrillation in Patients with Index Traumatic Intracranial Hemorrhage

The optimal time to restart direct oral anticoagulants (DOACs) for nonvalvular atrial fibrillation (NVAF) after traumatic intracranial hemorrhage (tICH) is unknown. Physicians must weigh the risk of recurrent hemorrhage against ischemic stroke. We investigated rates of stroke while holding anticoagulation, hemorrhage after anticoagulation resumption, and factors associated with the decision to restart anticoagulation. Patients presenting to our level I trauma center for tICH while on a DOAC for NVAF were retrospectively reviewed over 2 years. Age, sex, DOAC use, antiplatelet use, congestive heart failure, hypertension, age, diabetes, previous stroke, vascular disease, sex score for stroke risk in NVAF, injury mechanism, bleeding pattern, Injury Severity Score, use of a reversal agent, Glasgow Coma Scale at 24 hours, hemorrhage expansion, neurosurgical intervention, Morse Fall Risk, DOAC restart date, rebleed events, and ischemic stroke were recorded to study rates of recurrent hemorrhage and stroke, and factors that influenced the decision to restart anticoagulation. Twenty-eight patients sustained tICH while on a DOAC. Fall was the most common mechanism (89.3%), and subdural hematoma was the predominant bleeding pattern (60.7%). Of the 25 surviving patients, 16 patients (64%) restarted a DOAC a median 29.5 days after tICH. One patient had recurrent hemorrhage after resuming anticoagulation. One patient had an embolic stroke after 118 days off anticoagulation. Age >80, Injury Severity Score ≥16, and expansion of tICH influenced the decision to indefinitely hold anticoagulation. The low stroke rate observed in this study suggests that holding DOACs for NVAF for 1 month is sufficient to reduce the risk of stroke after tICH. Additional data are required to determine optimal restart timing.

Use of anticoagulant drugs in patients with atrial fibrillation. Does adherence to therapy have a prognostic impact?

Anticoagulant therapy represents a pivotal element that strongly influences the thromboembolic risk of non-valvular atrial fibrillation (NVAF) subjects. The main purpose of this review was to identify issues and suggest strategies to improve the oral anticoagulants (OACs) treatment adherence, which is the most important predictor of NVAF outcome. Advantages, efficacy, and impact of these drugs on patients' prognosis were revealed in important clinical trials on large cohorts of patients and are often prescribed nowadays. A real-life data registry, the Global Anticoagulant Registry in the Field-Atrial Fibrillation (GARFIELD-AF) analyzed the profile and outcome of patients diagnosed with NVAF receiving oral antithrombotic treatment. The observations gathered in the registry were crucial for identifying relevant elements that clinicians must improve, such as adherence strategies and predisposing factors that correlated with stroke. Adherence to OACs in AF patients is essential from the viewpoint of clinical efficacy and safety. Major adverse events and negative outcome are correlated with a weak anticoagulation control caused by an ineffective treatment adherence strategy. Solving the issue of oral anticoagulation adherence is possible using new technologies, but future directions should be explored. Mobile phone applications centered on patients' needs, telemedicine programs that evaluate patients' evolution and detect adverse reactions or events, encouraging an adequate management of the event without interruption of OACs, represent perspectives with a major impact on treatment adherence.

Abstract 13849: Association of Optimal Blood Pressure and Risk of Atrial Fibrillation in Aged Type 2 Diabetes Mellitus Patients: From the JPAD Cohort Study

Introduction: Even, both type 2 diabetes (T2DM) and hypertension are important risk factors for nonvalvular atrial fibrillation (NVAF), the efficacy of strict blood pressure control for prevention of NVAF have not been established. Hypothesis: We assessed the hypothesis that optimal blood pressure is associated with lower risk of NVAF among T2DM patients in long term cohort of aged Japanese T2DM patients, JPAD cohort study. Methods: The JPAD cohort study was a follow-up cohort study of the JPAD trial, which was a randomized, standard-care controlled trial examining whether low-dose aspirin prevented cardiovascular disease (CVD) events in 2535 Japanese patients with T2DM from 2002. After that trial ended in 2008, we followed up the patients until 2019. Optimal blood pressured was defined as systolic blood pressure &lt; 120 mm Hg at baseline regardless of use of antihypertensive drugs. The association of optimal blood pressure and risk of NVAF was evaluated by Cox proportional hazard model adjusted for conventional risk factors for CVD. We also performed subgroup analysis by use of antihypertensive drugs. Results: Mean age of participants was 65 ± 10 years. During the median follow up of 10.9 years, 132 patients developed NVAF. The adjusted hazard ratio (HR) and its 95% confidence interval (CI) of NVAF of T2DM patients with optimal blood pressure comparing to those with higher blood pressure was 0.89 (0.45-1.75). In subgroup analysis by use of antihypertensive drugs, the results were not altered. The risk of NVAF among patients with optimal blood pressure comparing to those with higher blood pressure among patients using antihypertensive drugs and those not using antihypertensive drugs were 1.08 (0.34-3.45) and 0.78 (0.34-1.79), respectively. Conclusions: Optimal blood pressure was not associated with lower risk of NVAF among aged T2DM patients. However, due to high risk profile of NVAF among aged T2DM patents, careful follow up may be still necessary for prevention of CVD.

Prediction of left atrial thrombus in patients with nonvalvular atrial fibrillation referred to catheter ablation or cardioversion: comparison of different risk scores

Abstract Funding Acknowledgements Type of funding sources: None. Background. Left atrial thrombus (LAT) is the main source of cardiac emboly in patients with non-valvular atrial fibrillation (NAF). Several risk scores – mostly modified CHADS2 and CHA2DS2-VASc – were offered to predict LAT in patients with NAF. However, their relative predictive value requires further evaluation. Purpose. Compare the ability of different risk scores to predict LAT before catheter ablation or cardioversion in patients with NAF. Methods. In a retrospective single-center study, medical records of 1994 patients with NAF who underwent transesophageal echocardiography before catheter ablation or cardioversion were analyzed. LAT was identified in 33 (1.6%) of them. For the control group 167 patients without LAT were randomly selected from this database. Logistic regression analysis and C-statistic were used for evaluation and comparison of predictive values of CHADS2, R2CHADS2, CHA2DS2-VASc, R-CHA2DS2-VASc, R2CHA2DS2-VASc, CHA2DS2-VASc-RAF, mCHA2DS2-VASc and CHA2DS2-VASc-AFR scores. Results. The mean age of studied patients was 60.3 ± 10.9 years, 110 (55%) of them were males. The mean CHA2DS2-VASc score was 2.54 ± 1.79. Results of univariate analysis and C-statistic for above mentioned risk scores are presented in the table. Each of them was associated with LAT. In comparison with a CHA2DS2-VASc score C-statistic was significantly higher for CHA2DS2-VASc-RAF and CHA2DS2-VASc-AFR scores (p values 0.03 and 0.001 respectively). In multivariate analysis only CHA2DS2-VASc-RAF score was associated with LAT (OR 1.37; 95% CI 1.21-1.55, p &amp;lt; 0.0001). OR for LАT in patients with CHA2DS2-VASc-RAF &amp;gt;3 was 12.8 (95% CI 3.75-43.9; p &amp;lt; 0.0001) with sensitivity, specificity, positive and negative predictive values 90.6%, 57.1%, 33.3% and 58.9% respectively. Conclusion. In a group of patients with NAF and relatively low incidence of LAT all studied scores were associated with LAT and CHA2DS2-VASc-RAF score has appeared the most informative. Predictors of LAT in patients with NAF Risk stratification models OR (95% CI) p-value C-statistic (95% CI) CHADS2 2.12 (1.55-2.91) &amp;lt;0.0001 0.77 (0.68-0.85) R2CHADS2 2.00 (1.53-2.62) &amp;lt;0.0001 0.78 (0.69-0.87) CHA2DS2-VASc 1.65 (1.36-2.05) &amp;lt;0.0001 0.74 (0.65-0.84) R-CHA2DS2-VASc 1.64 (1.34-2.03) &amp;lt;0.0001 0.76 (0.66-0.85) R2CHA2DS2-VASc 1.59 (1.32-1.92) &amp;lt;0.0001 0.76 (0.66-0.85) CHA2DS2-VASc- RAF 1.35 (1.27-1.52) &amp;lt;0.0001 0.84 (0.76-0.91) mCHA2DS2-VASc 1.83 (1.42-2.35) &amp;lt;0.0001 0.75 (0.65-0.85) CHA2DS2-VASc-AFR 1.75 (1.41-2.17) &amp;lt;0.0001 0.80 (0.71-0.88)

A Study of Cardiogenic Stroke Risk in Non-valvular Atrial Fibrillation Patients.

Objectives: We attempted to develop more precisely quantified risk models for predicting cardiogenic stroke risk in non-valvular atrial fibrillation (NVAF) patients.Methods: We conducted a case-control study, using data from hospitalized patients with AF who underwent transesophageal echocardiography at Shanghai Chest Hospital. A total of 233 high cardiogenic stroke risk patients with left atrial appendage thrombus (LAT) or left atrial spontaneous echo contrast (LA-SEC) and 233 controls matched for age, sex, AF type.Results: AF history, LA diameter enlargement, larger left ventricular end diastolic diameter, lower ejection fraction, greater serum uric acid (SUA), and brain natriuretic peptide (BNP) levels showed association with high stroke risk. The multivariate logistic regression analysis revealed that AF duration, left atrial diameter (LAd), left ventricular ejection fraction (LVEF), SUA, and BNP were independent risk factors of the LAT/LA-SEC. We used LAd, LVEF, SUA, and BNP to construct a combined predictive model for high stroke risk in NVAF patients (the area under ROC curve: 0.784; sensitivity 66.1%; specificity 76.8%; 95% CI 0.744–0.825, P < 0.001).Conclusion: Comprehensive evaluation of LAd, LVEF, SUA, and BNP may help stratify the cardiogenic stroke risk among non-valvular AF patients, guiding anticoagulation therapy.

Admission blood glucose level as an ischemic stroke risk modifier in patients with new-onset non-valvular atrial fibrillation

Abstract Background Several scores have been proposed to assess the stroke risk in patients with non-valvular atrial fibrillation (NVAF). However, type 2 diabetes mellitus (T2DM) is considered a major stroke risk factor regardless of glycemic control. Whether basal blood glucose level modifies the risk of stroke in NVAF is still unclear. Purpose To evaluate the risk of ischemic stroke according to the presence of T2DM and admission blood glucose (ABG) level in patients with new-onset NVAF starting direct oral anticoagulants (DOACs). Methods We analyzed all consecutive patients with NVAF at our outpatient clinic from January to December 2018. The study population was constituted by 1014 patients with new-onset NVAF starting DOACs. Baseline characteristics were evaluated in the overall cohort whereas outcomes were assessed for 915 patients. The median follow-up time was 19.6±12.9 months. Results Overall, 50.3% were male with a mean age of 73.9±12.5 years. Diabetic NVAF patients were more frequently male (p=0.04) with higher prevalence of dyslipidemia (p&amp;lt;0.001), hypertension (p&amp;lt;0.001), severe renal impairment (p=0.02), peripheral vasculopathy (p=0.007) and history of myocardial infarction (p&amp;lt;0.001) compared to non-diabetic NVAF. Conversely, no differences were observed between subgroups in terms of age (p=0.8). Baseline blood glucose level was significantly higher in the diabetic NVAF population (160±67 mg/dL vs 119±39 mg/dL; p&amp;lt;0.001). As expected, the mean CHA2DS2-VASc score was significantly higher in diabetic NVAF compared to non-diabetic group (4.7±1.4 vs 3.2±1.5; p&amp;lt;0.001). During a 2 year-follow up period, we collected 27 (3.0%) ischemic stroke. As expected, the rates of stroke were significantly higher in diabetic NVAF (7.6% vs 2.3%, p&amp;lt;0.001). Also, the ABG was significantly greater in NVAF who had an ischemic stroke compared to others (160±68 mg/dL vs 119±39 mg/dL, p=0.005). The incidence of stroke was almost five-time greater in NVAF with ABG level major than 150 mg/dl (9.8% vs 1.9%, p&amp;lt;0.001). At multivariate Cox-regression model adjusted for age, sex and presence of T2DM, blood glucose level at admission was the only independent predictor of ischemic stroke at follow up (HR 1.01, 95% CI 1.001–1.02; p=0.03). Finally, another multivariate Cox-regression model, adjusted for the mean CHA2DS2-VASc score, showed that the ABG level still remained a strong independent predictor of ischemic stroke at follow up (HR 1.012, 95% CI 1.003–1.02; p=0.01). Conclusions Diabetic NVAF had a worse baseline profile and higher stroke risk compared to non-diabetic NVAF. Baseline blood glucose level was an independent predictor of stroke regardless of the presence of T2DM or stroke risk profile. These findings underline the role of basal blood glucose level as a potential stroke risk modifier and therefore emphasize the importance of its routine determination to better stratify the stroke risk in NVAF starting DOACs. Funding Acknowledgement Type of funding source: None

Predictive value of four score systems on the bleeding risk in atrial fibrillation patients treated with dabigatran

Objective: To compare the predictive value of HAS-BLED, HEMORR2HAGES, ATRIA and ORBIT scores on the bleeding risk in nonvalvular atrial fibrillation (NVAF) patients treated with dabigatran. Methods: Data of 942 NVAF patients participating a non-interventional prospective study of anticoagulant therapy with dabigatran, which was conducted in 12 centers from February 2015 to December 2017 in China, were analyzed. Complete HAS-BLED HEMORR2HAGES, ATRIA and ORBIT bleeding risk scores data and follow-up data were available in the enrolled patients. The endpoint of the study was bleeding events occurred during a 6 months follow-up. Cox proportional hazards models were constructed to analyze the associations between HAS-BLED, HEMORR2HAGES, ATRIA and ORBIT scores and risk of bleeding, and the area under the curve (AUC) of receiver operating characteristics curves (ROC) of each score was used to set the predictive value for bleeding risk. Results: Among the 942 patients, the mean age was (65.3±11.2) years old, 542 (57.5%) were males. A total of 93 (9.9%) bleeding events occurred during follow up, 89 (9.4%) events were minor bleeding, and 4 (0.4%) events were major bleeding. Patients with a high-risk HAS-BLED score had a 1.87-fold increased risk of bleeding compared with low-risk patients (HR = 2.87, 95% CI:1.26-6.51, P = 0.012). There was no statistically significant difference between low-medium-high-risk grading in other scoring systems and bleeding risk (all P>0.05). The AUC (95%CI) of HAS-BLED, HEMORR2HAGES, ATRIA and ORBIT bleeding risk scores were 0.558 (0.525-0.590), 0.520 (0.487-0.553), 0.513(0.480-0.545), 0.523(0.490-0.555), respectively. The AUC of all bleeding score systems were of ≤ 0.700. Conclusion: Among the NVAF patients taking dabigatran in China, the HAS-BLED bleeding risk score is superior to other 3 bleeding risk score on predicting the bleeding risk in these patients, but its predictive value is still relatively low.

P1360Association between left atrial appendage dysfunction and thromboembolic risk in nonvalvular atrial fibrillation

Abstract Background/Introduction: Atrial fibrillation (AF) is associated with higher risk for thromboembolism , and the discriminative ability of the widely used CHA2DS2-VASc scores for risk stratification is modest. Although the presence of thrombus in the LAA is the most powerful predictors for thromboembolic risk, they are often absent in patients with AF and prior stroke. AF may be related to myocardial fibrosis, and even though left atrial fibrosis is associated with mechanical dispersion, this phenomenon is not well studied in LAA. We hypothesized that detection of LAA dysfunction and mechanical dispersion using strain echocardiography is useful in the identification of cardiac thromboembolism. Purpose The aim of this study was to determine the association of LAA mechanics assessed using strain analysis with previous thromboembolic events in patients with nonvalvular AF and to assess the potential incremental significance of LAA mechanical dispersion over the traditional risk stratification scheme. Methods A group of 116 patients with AF referred for TEE was prospectively analyzed. LAA strain and mechanical dispersion in parallel with other conventional TEE parameters were analyzed in terms of their association with previous embolic stroke and peripheral embolization. Results Patients with embolic events had a higher mean CHA2DS2-VASc score, higher incidence of LAA dense SEC or thrombi, and other clinical data were comparable. Patients with embolic events had greater impairment in the LA standard parameters, and lower global and regional LAA longitudinal strain than those of the controls. LAA MD was significantly higher in patients with embolization than in those without it (18.91 ± 7.19 %vs 13.8 ± 5.54%; P &amp;lt; .001). In ROC analysis, cut-off values for LAA MD,LAEF, LAA GLS for the presence of dense SEC/ thrombus were &amp;gt;20.21 % (p = 0.0076), ≤31.11 % (p = 0.017), and ≤ 7.31 % (p = 0.014), respectively. LAA MD, LAEF, LAA thrombus and CHA2DS2-VASc scores were independently associated with the presence of thromboembolism in multivariate analyses, and LAA MD had additional significance over the CHA2DS2-VASc score. Conclusion LAA MD, LAA thrombi and LAEF had statistically significant meaning for the presence of prior embolism that was independent of the standard planimetric and volumetric measurements. What’s more, LAA MD had an incremental value over CHA2DS2-VASc score in risk stratification and warrants testing in a larger study. Abstract Figure. ROC curves for LAA parameters

New Uses of Platelet-Lymphocyte Ratio for Bleeding Risk Stratification in Patients with Nonvalvular Atrial Fibrillation: A Pilot Study

Objective: The primary aim of this study was to investigate the role of platelet-lymphocyte ratio (PLR) to predict bleeding risk in nonvalvular atrial fibrillation (NVAF). Secondary aim was to determine the possible relation between PLR and thromboembolic and bleeding risk scores. Tertiary aim was to evaluate the predictive value of PLR for the patients in the therapeutic international normalized ratio (INR) range. Method: PLR was calculated from the complete blood count of 228 patients who were under warfarin management for NVAF. The patients were called and it was questioned whether they had experienced the bleeding event within six months after measurement of the PLR values. Results: Bleeding event was observed in 48 patients after the PLR was calculated. It was found significantly correlation between PLR and CHA2DVAS2C (p 165,9 was determined significant indicator for bleeding (p<0.001) and showed more than a 12-fold increased risk of bleeding (12.27, [5.74-26.21]). Conclusions: The results of the present study indicate that the PLR might be a useful parameter to detect the risk of bleeding. To our knowledge, this is the first study demonstrating the correlation of PLR with both CHA2DS2-VASc and HAS-BLED risk scores. PLR may also predict the patients within the therapeutic INR range.

Persistent Systemic Inflammation Is Associated With Bleeding Risk in Atrial Fibrillation Patients.

This study investigated the impact of systemic inflammation on bleeding risk in non-valvular atrial fibrillation (NVAF) patients treated with direct oral anticoagulants (DOAC).Methods and Results:We conducted a single-center prospective registry of 2,216 NVAF patients treated with DOAC: the DIRECT registry (UMIN000033283). High-sensitivity C-reactive protein (hsCRP) was measured ≤3 months before (pre-DOAC hsCRP) and 6±3 months after initiation of DOAC (post-DOAC hsCRP). Multivariate logistic regression model was used to assess the influence of systemic inflammation and conventional bleeding risk factors on major bleeding according to International Society on Thrombosis and Haemostasis criteria. Based on the findings, we created a new bleeding risk assessment score: the ORBIT-i score, which included post-DOAC hsCRP >0.100 mg/dL and all components of the ORBIT score. A total of 1,848 patients had both pre- and post-DOAC hsCRP data (follow-up duration, 460±388 days). Post-DOAC hsCRP was associated with major bleeding (OR, 2.770; 95% CI: 1.687-4.548, P<0.001). Patients with post-DOAC hsCRP >0.100 mg/dL more frequently had major bleeding than those without (log-rank test, P<0.001). ORBIT-i score had the highest C-index of 0.711 (95% CI, 0.654-0.769) compared with the ORBIT and HAS-BLED scores. Persistent systemic inflammation was associated with major bleeding risk. ORBIT-i score had a higher discriminative performance compared with the conventional bleeding risk scores.

P814 Independent association of body mass index and left atrial strain in patients with non valvular atrial fibrillation. The NeAfib-Echo registry

Abstract Background Overweight and obesity are related to the risk of new-onset atrial fibrillation (AF). Peak atrial longitudinal strain (PALS) is an advanced echocardiographic parameter of left atrial (LA) function with a recognized diagnostic and prognostic role in both the general population and AF. Purpose To investigate the impact of body mass index (BMI) on LA function by utilizing standard and advanced echocardiography in patients with non-valvular AF. Methods In the NeAfib-Echo registry, 395 consecutive adult patients with non-valvular AF (F/M: 175/220; mean age 70.6 ± 11 years, BMI: 27.8 ± 5.6 kg/m²) were enrolled. 215 patients (54.1%) had permanent/persistent AF (prAF) and 178 (45.9%) had paroxysmal AF (pxAF). Anthropometric parameters and blood pressure (BP) were recorded and CHA2DS2VASc score was calculated. Patients underwent a complete echo-Doppler exam, including determination of PALS and left ventricular (LV) global longitudinal strain (GLS) (both reported in absolute values). The overall population was divided according to BMI tertiles: first tertile &amp;lt;25.3 Kg/m² (n = 127); second tertile 25.3-29 Kg/m² (n = 137); third tertile &amp;gt; 29.3 Kg/m² (n = 130). Results No significant difference of sex prevalence, age, systolic BP and heart rate was found among the three BMI tertiles, whereas diastolic BP was higher in the third tertile (p &amp;lt; 0.001). CHA2DS2VASc score did not significantly differ among tertiles. In the pooled population LV mass index (LVMi) (p = 0.001) progressively increased from the first to the third tertile (p &amp;lt; 0.001), whereas LA volume index, LV ejection fraction (EF), GLS and E/e" ratio were not significantly different among the three groups. PALS was lower in third tertile (14.3 ± 8.2%) versus both the first (19.0 ± 11.5%) and the second tertile (17.7 ± 10.6%) (p &amp;lt; 0.002). In separate sub-analyses according to AF type, PALS was significantly lower in the first than the third tertile in the PxAF group (p &amp;lt; 0.01) but not in patients with PrAF (p = 0.158). In the pooled population PALS was significantly related with BMI (r= -0.17, p &amp;lt; 0.001) (Figure) but also with age, heart rate, LVMi, LV EF, GLS, E/e’ ratio and pulmonary artery systolic pressure (PAPS). By a multilinear regression analysis, after adjusting for CHA2DS2VASc score, LV mass index, LV EF, E/e’ ratio and PAPs, BMI remained independently associated with PALS (standardized β coefficient = -0.127, p &amp;lt; 0.02) (cumulative R² =0.41, SEE = 8.5%, p &amp;lt; 0.0001). Conclusions In patients with non valvular AF, overweight and obesity exert a detrimental effect on LA function as testified by the gradual PALS reduction with the increase of BMI tertiles. BMI is associated with PALS independently of several confounders including CHA2DS2VASc. Besides CHA2DS2VASc score, BMI could be considered as an additional factor for evaluating cardiovascular risk in non valvular AF. Abstract P814 Figure. Relation between BMI and PALS

Usefulness of CHA2 DS2 -VASc score to predict mortality and hospitalization in patients with inflammatory arthritis.

Inflammatory arthritis including rheumatoid arthritis (RA), ankylosing spondylitis (AS) and psoriatic arthritis (PsA) are disorders at increased risk of morbidity and mortality for which a validated prognostic tool for facilitating clinical management is needed. CHA2 DS2 -VASc (congestive heart failure/hypertension/age diabetes/stroke/vascular disease/age/sex category) score was initially conceived and used to estimate thromboembolic risk in non-valvular atrial fibrillation, and then successfully applied in community populations with sinus rhythm. We tested CHA2 DS2 -VASc-score as a prognosticator of adverse outcomes in patients in sinus rhythm with RA/AS/PsA. Between March 2014 and March 2015, 414 patients (214 RA, 75 AS, 125 PsA) in sinus rhythm without cardiac disease were consecutively analyzed and prospectively followed-up. Primary and co-primary end-points were a composite of all-cause death/all-cause hospitalization and CV death/CV hospitalization, respectively. Patients were divided into LOWscore and HIGHscore groups if CHA2 DS2 -VASc was=0/1 point or greater than 1 point, respectively. The HIGHscore group comprised 190 patients who were older with higher prevalence of CV risk factors and arthritis disease activity than 224 LOWscore patients. During a follow up of 36months, the event rate for primary and co-primary end-point was 37% and 12% in the HIGHscore vs 22% and 4% in LOWscore group (P=.001 and .002 respectively). At multivariate Cox regression analysis CHA2 DS2 -VASc-score was related to primary end-point (hazards ratio [HR] 1.30 [1.07-1.59], P=.009) and co-primary end-point (HR 1.35 [1.01-1.79], P=.04) independently of traditional CV risk factors analyzed individually and indexes of inflammation or disease duration. CHA2 DS2 -VASc-score accurately identifies in the mid-term patients in sinus rhythm with RA/AS/PsA at different risks for CV and non-CV mortality and hospitalization.

PCV127 PATIENT PREFERENCES REGARDING ORAL ANTICOAGULANTS: RESULTS OF A DISCRETE CHOICE EXPERIMENT IN SPANISH PATIENTS WITH ATRIAL FIBRILLATION TREATED WITH VITAMIN-K ANTAGONISTS

Oral anticoagulation is pivotal in the management of thromboembolic risk in non-valvular atrial fibrillation (NVAF) patients. An effective anticoagulation therapy also relates on good medication adherence to achieve good anticoagulation control. One key element for reaching or sustaining a good adherence and persistence is to prescribe treatments that patients prefer. The objective of this study was to elucidate patient preferences regarding attributes that describe different anticoagulation alternatives. A multi-center discrete choice experiment (DCE) was conducted in Spain. Study sites enrolled patients aged 18+ years with NVAF, who initiated a Vitamin-K antagonist (VKA) treatment. The DCE design considered four treatment attributes: need of bridging (yes/no), interactions with food/alcohol (yes/no), need of regular international normalized ratio (INR) assessments/blood controls and subsequent dose adjustment (yes/no) and frequency of intake (once/twice daily). Distance to treating practitioner represented a neutral attribute to express patients’ overall utility in terms of a comprehensible unit. Conditional logit regression model was applied to estimate patients’ utility for each attribute and to evaluate the influence of different levels on the probability of a patient of choosing a specific OAC alternative. In total, 286 patients were included (mean age: 72.9 years, 42.0% female, mean CHA2DS2-VASc: 3.2). Patients preferred an anticoagulation treatment option characterized by “no need for bridging” (β=0.530, p<0.001), “no need for regular INR controls” (β=0.652, p<0.001), “less interactions with food/alcohol” (β=0.503, p<0.001) and “once daily intake” (β=0.360, p<0.001). To receive such a treatment option compared to a treatment that offers none of the favourable characteristics, the average patient would be willing to travel additional 57 kilometres to the treating practitioner. In our study, NVAF patients currently treated with VKA showed a strong preference for features that characterize non-VKA anticoagulation options.

Apixaban: A Clinical Pharmacokinetic and Pharmacodynamic Review.

Apixaban is an oral, direct factor Xa inhibitor that inhibits both free and clot-bound factor Xa, and has been approved for clinical use in several thromboembolic disorders, including reduction of stroke risk in non-valvular atrial fibrillation, thromboprophylaxis following hip or knee replacement surgery, the treatment of deep vein thrombosis or pulmonary embolism, and prevention of recurrent deep vein thrombosis and pulmonary embolism. The absolute oral bioavailability of apixaban is ~ 50%. Food does not have a clinically meaningful impact on the bioavailability. Apixaban exposure increases dose proportionally for oral doses up to 10 mg. Apixaban is rapidly absorbed, with maximum concentration occurring 3–4 h after oral administration, and has a half-life of approximately 12 h. Elimination occurs via multiple pathways including metabolism, biliary excretion, and direct intestinal excretion, with approximately 27% of total apixaban clearance occurring via renal excretion. The pharmacokinetics of apixaban are consistent across a broad range of patients, and apixaban has limited clinically relevant interactions with most commonly prescribed medications, allowing for fixed dosages without the need for therapeutic drug monitoring. The pharmacodynamic effect of apixaban is closely correlated with apixaban plasma concentration. This review provides a summary of the pharmacokinetic, pharmacodynamic, biopharmaceutical, and drug–drug interaction profiles of apixaban. Additionally, the population-pharmacokinetic analyses of apixaban in both healthy subjects and in the target patient populations are discussed.