Oral anticoagulant safety in family practice: prognostic accuracy of Bleeding Risk Scores (from the CACAO study).

BACKGROUND: To assess bleeding risk of patients treated by oral anticoagulants, several scores have been constructed to assist physicians in the evaluation of the benefit risk. Most of these scores lack a strong enough level of evidence for use in family practice. OBJECTIVE: To assess the predictive prognostic accuracy of 13 scores designed to assess the risk of major or clinically relevant non-major (CRNM) bleeding events in a French ambulatory cohort receiving Vitamin-K antagonists (VKA) or direct oral anticoagulants (DOACs) in a family practice setting. METHODS: CACAO (Comparison of Accidents and their Circumstances with Oral Anticoagulants) was a multicentre prospective cohort of ambulatory patients prescribed oral anticoagulants. We selected patients from the cohort who had received an oral anticoagulant because of non-valvular atrial fibrillation (NVAF) and/or venous thromboembolism (VTE) to be followed during one year by their GP. The following scores were calculated: mOBRI, Shireman, Kuijer, HEMORR2HAGES, ATRIA, HAS-BLED, RIETE, VTE-BLEED, ACCP score, Rutherford, ABH-Score, GARFIEL-AF, and Outcomes Registry for Better InformedTreatment of Atrial Fibrillation (ORBIT). Prognostic accuracy was assessed by using receiver operating characteristic curves and c-statistics. RESULTS: During 1 year, 3,082 patients were followed. All of the scores demonstrated only poor to moderate ability to predict major bleeding or CRNM in NVAF patients on DOACs (c-statistic: 0.41-0.66 and 0.45-0.58), respectively. The results were only slightly better for patients prescribed VKA (0.47-0.66 and 0.5-0.55, respectively) in this indication. The results were also unsatisfactory in patients treated for VTE. CONCLUSION: None of the scores demonstrated satisfactory discriminatory ability when used in family practice. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT02376777.

Demographic, clinical, and functional determinants of antithrombotic treatment in patients with nonvalvular atrial fibrillation.

BACKGROUND: This study assessed the sociodemographic, functional, and clinical determinants of antithrombotic treatment in patients with nonvalvular atrial fibrillation (NVAF) attended in the internal medicine setting. METHODS: A multicenter, cross-sectional study was conducted in NVAF patients who attended internal medicine departments for either a routine visit (outpatients) or hospitalization (inpatients). RESULTS: A total of 961 patients were evaluated. Their antithrombotic management included: no treatment (4.7%), vitamin K antagonists (VKAs) (59.6%), direct oral anticoagulants (DOACs) (21.6%), antiplatelets (6.6%), and antiplatelets plus anticoagulants (7.5%). Permanent NVAF and congestive heart failure were associated with preferential use of oral anticoagulation over antiplatelets, while intermediate-to high-mortality risk according to the PROFUND index was associated with a higher likelihood of using antiplatelet therapy instead of oral anticoagulation. Longer disease duration and institutionalization were identified as determinants of VKA use over DOACs. Female gender, higher education, and having suffered a stroke determined a preferential use of DOACs. CONCLUSIONS: This real-world study showed that most elderly NVAF patients received oral anticoagulation, mainly VKAs, while DOACs remained underused. Antiplatelets were still offered to a proportion of patients. Longer duration of NVAF and institutionalization were identified as determinants of VKA use over DOACs. A poor prognosis according to the PROFUND index was identified as a factor preventing the use of oral anticoagulation.

Efficacy of R2CHA2DS2-VA score for predicting thromboembolism in Thai patients with non-valvular atrial fibrillation.

BACKGROUND: There is no data specific to the addition of renal dysfunction and age 50-64 years as risk parameters to the CHA2DS2-VA score, which is known as the R2CHA2DS2-VA score, among NVAF patients. Accordingly, the aim of this study was to validate the R2CHA2DS2-VA score for predicting thromboembolism in Thai NVAF patients. METHODS: Thai NVAF patients were prospectively enrolled in a nationwide multicenter registry from 27 hospitals during 2014-2020. Each component of the CHA2DS2-VA and R2CHA2DS2-VA scores was scored and recorded. The main outcomes were thromboembolism, including ischemic stroke, transient ischemic attack (TIA), and/or systemic embolism. The annual incidence rate of thromboembolism among patients in each R2CHA2DS2-VA and CHA2DS2-VA risk score category is shown as hazard ratio (HR) and 95% confidence interval (95% CI). The performance of the R2CHA2DS2-VA and CHA2DS2-VA scores was demonstrated using c-statistics. Net reclassification index was calculated. Calibration plat was used to assess agreement between observed probabilities and predicted probabilities of both scoring system. RESULTS: A total of 3402 patients were enrolled during 2014-2020. The average age of patients was 67.38 ± 11.27 years. Of those, 46.9% had renal disease, 30.7% had a history of heart failure, and 17.1% had previous stroke or TIA. The average R2CHA2DS2-VA and CHA2DS2-VA scores were 3.92 ± 1.92 and 2.98 ± 1.43, respectively. Annual thromboembolic risk increased with incremental increase in R2CHA2DS2-VA and CHA2DS2-VA scores. Oral anticoagulants had benefit in stroke prevention in NVAF patients with an R2CHA2DS2-VA score of 2 or more (adjusted HR: 0.630, 95% CI 0.413-0.962, p = 0.032). The c-statistics were 0.630 (95% CI 0.61-0.65) and 0.627 (95% CI 0.61-0.64), for R2CHA2DS2-VA and CHA2DS2-VA scores respectively. NRI was 2.2%. The slope and R2 of the calibration plot were 0.73 and 0.905 for R2CHA2DS2-VA and 0.70 and 0.846 for CHA2DS2-VA score respectively. CONCLUSIONS: R2CHA2DS2-VA score was found to be at least as good as CHA2DS2-VA score for predicting thromboembolism in Thai patients with NVAF. Similar to CHA2DS2-VA score, thromboembolism increased with incremental increase in R2CHA2DS2-VA score.

Identification and early anticoagulation in patients with atrial fibrillation in the emergency department.

BACKGROUND: Emergency departments (ED) in the United States see more than half a million atrial fibrillation visits a year, however guideline recommended anticoagulation is prescribed in <55% of eligible patients. OBJECTIVE: The purpose of this study was to measure guideline recommended anticoagulation prescribing in patients with nonvalvular atrial fibrillation (NVAF) presenting to the ED, with the goal of closing any treatment gap established. METHODS: We conducted an observational, prospective cohort study in consecutive patients presenting to the ED with a diagnosis of NVAF. CHA2DS2-VASc and HAS-BLED scores were calculated and used as predefined criteria to establish guideline-based oral anticoagulation compliance in comparing routine care (baseline cohort) versus a multidisciplinary team approach. Transition of Care (TOC) services and follow-up were also provided in the multidisciplinary cohort. The primary endpoint was to compare the proportion of patients on guideline based oral anticoagulant (OAC) therapy at admission and discharge between the groups. RESULTS: In the Baseline Cohort (BC) (n = 99), 62.3% of patients with a moderate-high risk of stroke (CHA2DS2-VASc score ≥ 2) were discharged on guideline-based OAC therapy versus 87.8% in the Multidisciplinary Team Cohort (MTC) (n = 131), a 25.5% overall improvement for appropriate anticoagulation (p-value <.001, 95% CI (0.14-0.37)). CONCLUSIONS: A multidisciplinary team approach with TOC services for the identification and early intervention of NVAF patients at risk of stroke in the ED can significantly improve the percentage of moderate to high-risk patients that are discharged home with guideline based OAC.

Using Artificial Intelligence With Natural Language Processing to Combine Electronic Health Record's Structured and Free Text Data to Identify Nonvalvular Atrial Fibrillation to Decrease Strokes and Death: Evaluation and Case-Control Study.

BACKGROUND: Nonvalvular atrial fibrillation (NVAF) affects almost 6 million Americans and is a major contributor to stroke but is significantly undiagnosed and undertreated despite explicit guidelines for oral anticoagulation. OBJECTIVE: The aim of this study is to investigate whether the use of semisupervised natural language processing (NLP) of electronic health record's (EHR) free-text information combined with structured EHR data improves NVAF discovery and treatment and perhaps offers a method to prevent thousands of deaths and save billions of dollars. METHODS: We abstracted 96,681 participants from the University of Buffalo faculty practice's EHR. NLP was used to index the notes and compare the ability to identify NVAF, congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke or transient ischemic attack, vascular disease, age 65 to 74 years, sex category (CHA2DS2-VASc), and Hypertension, Abnormal liver/renal function, Stroke history, Bleeding history or predisposition, Labile INR, Elderly, Drug/alcohol usage (HAS-BLED) scores using unstructured data (International Classification of Diseases codes) versus structured and unstructured data from clinical notes. In addition, we analyzed data from 63,296,120 participants in the Optum and Truven databases to determine the NVAF frequency, rates of CHA2DS2­VASc ≥2, and no contraindications to oral anticoagulants, rates of stroke and death in the untreated population, and first year's costs after stroke. RESULTS: The structured-plus-unstructured method would have identified 3,976,056 additional true NVAF cases (P<.001) and improved sensitivity for CHA2DS2-VASc and HAS-BLED scores compared with the structured data alone (P=.002 and P<.001, respectively), causing a 32.1% improvement. For the United States, this method would prevent an estimated 176,537 strokes, save 10,575 lives, and save >US $13.5 billion. CONCLUSIONS: Artificial intelligence-informed bio-surveillance combining NLP of free-text information with structured EHR data improves data completeness, prevents thousands of strokes, and saves lives and funds. This method is applicable to many disorders with profound public health consequences.

Non-Vitamin K-Dependent Oral Anticoagulants for Nonvalvular Atrial Fibrillation in Patients With CKD: Pragmatic Considerations for the Clinician.

Management of atrial fibrillation (AF) in patients with advanced chronic kidney disease (CKD) poses a complex conundrum because of higher risks for both thromboembolic and bleeding complications compared to the general population. This makes it particularly important for clinicians to carefully weigh the risks versus benefits of anticoagulation therapy to determine the individualized net clinical benefit for every patient. During the past few years, 4 non-vitamin K-dependent oral anticoagulant (NOAC) agents have supplemented warfarin in the therapeutic armamentarium for the prevention of systemic thromboembolism in nonvalvular AF. However, the use of NOACs in CKD specifically mandates a nuanced understanding due to their varying dependence on renal clearance, with resultant safety implications related to either underdosing (thromboembolism) or excessive drug exposure (bleeding). This pragmatic review highlights unique considerations pertaining to accurate estimation and temporal monitoring of kidney function in the context of NOAC use with specific clinical deliberations and variables when determining whether an NOAC is appropriate for a patient with CKD. The dependence of NOACs on renal clearance and several troubling safety signals in the published literature suggest that it is vital for nephrologists to be active members of a multidisciplinary team caring for these high-risk patients with CKD and AF.

Successful Tissue Plasminogen Activator for a Patient with Stroke After Stanford Type A Aortic Dissection Treatment.

Some stroke patients with the acute aortic dissection receiving thrombolysis treatment resulted in fatalities. Thus, the concurrent acute aortic dissection is the contraindication for the intravenous recombinant tissue-type plasminogen activator. However, the safety and the effectiveness of the intravenous recombinant tissue-type plasminogen activator therapy are not known in patients with stroke some days after acute aortic dissection treatment. Here, we first report a case of a man with a cardioembolism due to the nonvalvular atrial fibrillation, who received the intravenous recombinant tissue-type plasminogen activator therapy 117 days after the traumatic Stanford type A acute aortic dissection operation. Without the intravenous recombinant tissue-type plasminogen activator therapy, the prognosis was expected to be miserable. However, the outcome was good with no complication owing to the intravenous recombinant tissue-type plasminogen activator therapy. Our case suggests the effectiveness and the safety of the intravenous recombinant tissue-type plasminogen activator therapy to the ischemic stroke some days after acute aortic dissection treatment.

Non-Vitamin K Oral Anticoagulants (NOACs) and Their Reversal.

PURPOSE OF REVIEW: An 80-year-old man presents with an acute right hemiparesis and National Institutes of Health Stroke Scale (NIHSS) of 25, 14 h after taking dabigatran. Activated partial thromboplastin time (aPTT) is 42.8 s. Arteriogram demonstrates left internal carotid artery thrombosis. What is the appropriate management of this patient with acute ischemic stroke while on a NOAC? RECENT FINDINGS: Idarucizumab is a reversal agent approved for dabigatran, and two more reversal agents, andexanet alfa and aripazine, are currently in development for NOACs. In this article, we review currently available NOACs, their laboratory monitoring, and reversal agents.

Management and Outcomes of Bleeding Events in Patients in the Emergency Department Taking Warfarin or a Non-Vitamin K Antagonist Oral Anticoagulant.

BACKGROUND: Most comparisons of bleeding patients who are taking warfarin or a non-vitamin K oral anticoagulant (NOAC) have been limited to admitted patients and major bleeding events in well-controlled, clinical trial settings. OBJECTIVES: We describe the clinical characteristics, interventions, and outcomes in patients who are taking warfarin or a NOAC who presented to the emergency department (ED) with any bleeding event. METHODS: We conducted a structured, retrospective, observational study of nonvalvular atrial fibrillation, pulmonary embolism, or deep vein thrombosis warfarin- or NOAC-treated patients presenting with any bleeding event to a large, academic ED between January 2012 and March 2015. We used descriptive statistics to summarize baseline characteristics, treatments, and outcomes and performed subgroup analyses based on the type of anticoagulant and site of bleeding. RESULTS: The electronic search yielded 95 cases of patients taking a NOAC (i.e., dabigatran [33], rivaroxaban [32], or abixaban [30]) and 342 patients taking warfarin. Reversal agents were rarely used in all anticoagulant groups. Case fatality rates were similar among warfarin- and NOAC-treated patients for gastrointestinal bleeding (7% vs. 7%) and intracranial hemorrhage (18% vs. 4%), respectively. After adjustment for other factors, only intracranial hemorrhage (odds ratio 4.4; 95% confidence interval 1.4-13.3) was associated with mortality. CONCLUSIONS: Despite the rare use of reversal strategies, mortality was low and outcomes were comparable among patients with bleeding events presenting to the ED while taking a NOAC compared with warfarin.

Associations between waist circumference, central obesity, and the presence of non-valvular atrial fibrillation patients with heart failure.

Background: Reportedly, there is a clear correlation between waist circumference (WC) and atrial fibrillation (AF). However, there is no specific discussion about the relationship between WC and non-valvular AF (NVAF) patients with heart failure. Our main purpose was to study the relationship between WC, central obesity (CO), and NVAF patients with heart failure. Methods: This is a retrospective cohort study. A total of 3,435 patients with NVAF in the First Affiliated Hospital of Xinjiang Medical University from January 2015 to December 2017 were enrolled. The targeted independent variable and the dependent variable were WC and CO and the presence of NVAF with heart failure, respectively. Univariate, multiple regression, and subgroup analyses were used to analyze their relationship. We used the receiver operating characteristic (ROC) curve to choose the better predictor of NVAF with heart failure between WC and CO and calculated the proposed cut-off value of WC in males and female separately. Results: The identified risk factors of NVAF with heart failure were sex, height, WC, CO, body mass index (BMI), fasting blood glucose (FBG), homocysteine (HCY), triglyceride (TG), low-density lipoprotein cholesterol (LDLC), hypertension, diabetes mellitus (DM), stroke, vascular disease, and plaque. Then, a binary logistic regression model indicated that the occurrence of NVAF patients with heart failure increased 10% with WC increasing 1 cm and had a 2.8-fold increased risk with CO compared to those without. The predictive value [area under the ROC curve (AUC)], specificity, sensitivity, and accuracy of WC for the disease risk of NVAF with heart failure were higher than those of CO. The proposed cut-off value of WC was 91.85 cm for males and 93.15 cm for females. The diagnostic value of WC for NVAF with heart failure was higher for females than it was for males. Conclusions: Our research found that WC is related to the presence of heart failure in the patients with NYAF and can predict the presence of NVAF with heart failure. Our findings may help to improve the treatment and care strategies of NVAF individuals with abdominal obesity.

Safety and effectiveness of rivaroxaban for prevention of stroke in patients with nonvalvular atrial fibrillation: analysis of routine clinical data from four countries.

BACKGROUND: The safety and effectiveness of rivaroxaban versus vitamin K antagonists (standard of care [SOC]) for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF) was evaluated in Europe. RESEARCH DESIGN AND METHODS: Observational studies were conducted in the UK, the Netherlands, Germany, and Sweden. Primary safety outcomes were hospitalization for intracranial hemorrhage, gastrointestinal bleeding, or urogenital bleeding among new users of rivaroxaban and SOC with NVAF; outcomes were analyzed using cohort (rivaroxaban or SOC use) and nested case-control designs (current vs nonuse). Statistical analyses comparing rivaroxaban and SOC cohorts were not performed. RESULTS: Overall, 162,919 rivaroxaban users and 177,758 SOC users were identified. In the cohort analysis, incidence ranges for rivaroxaban users were 0.25-0.63 events per 100 person-years for intracranial bleeding, 0.49-1.72 for gastrointestinal bleeding, and 0.27-0.54 for urogenital bleeding. Corresponding ranges for SOC users were 0.30-0.80, 0.30-1.42, and 0.24-0.42, respectively. In the nested case-control analysis, current SOC use generally presented a greater risk of bleeding outcomes than nonuse. Rivaroxaban use (vs nonuse) was associated with a higher risk of gastrointestinal bleeding, but a similar risk of intracranial or urogenital bleeding, in most countries. Ischemic stroke incidence ranged from 0.31 to 1.52 events per 100 person-years for rivaroxaban users. CONCLUSIONS: Incidences of intracranial bleeding were generally lower with rivaroxaban than with SOC, whereas incidences of gastrointestinal and urogenital bleeding were generally higher. The safety profile of rivaroxaban for NVAF in routine practice is consistent with findings from randomized controlled trials and other studies.

Prolonged Secondary Stroke Prevention with Edoxaban: A Long-Term Follow-Up of the SATES Study.

BACKGROUND: Little evidence is available on the long-term efficacy and safety of edoxaban, mainly due to the recent release date. The primary objective of the study was to evaluate the safety of edoxaban, defined by the incidence of major bleedings. We then aimed to evaluate the incidence of thromboembolic events and the persistence of edoxaban therapy in the long-term. METHODS: In this observational cohort study, we included ischemic stroke patients enrolled in a previous study to evaluate the safety and efficacy of long-term edoxaban treatment. Data were collected by a trained investigator through a structured telephone interview. RESULTS: Sixty-three subjects (median age 81.0 (73.5-88.0) years, 38.1% male) were included in the study, with a mean follow-up of 4.4 ± 0.7 years (range: 3.2-5.5 years). Only one patient (1.6%, 0.4%/year) presented a major extracranial bleeding, and none had cerebral hemorrhage. Six thromboembolic events occurred in five patients (7.9%): three recurrent strokes, two transient ischemic attacks, and one myocardial infarction (2.2%/year). Over a follow-up period of more than three years, 13 patients discontinued edoxaban (20.6%). Conclusions: Edoxaban seems to be effective and safe in the long-term. The persistence rate of edoxaban therapy is optimal after more than three years of treatment.

The Distribution of the Genotypes of ABCB1 and CES1 Polymorphisms in Kazakhstani Patients with Atrial Fibrillation Treated with DOAC.

Nowadays, direct oral anticoagulants (DOACs) are the first-line anticoagulant strategy in patients with non-valvular atrial fibrillation (NVAF). We aimed to identify the influence of polymorphisms of the genes encoding P-glycoprotein (ABCB1) and carboxylesterase 1 (CES1) on the variability of plasma concentrations of DOACs in Kazakhstani patients with NVAF. We analyzed polymorphisms rs4148738, rs1045642, rs2032582 and rs1128503 in ABCB1 and rs8192935, rs2244613 and rs71647871 CES1 genes and measured the plasma concentrations of dabigatran/apixaban and biochemical parameters in 150 Kazakhstani NVAF patients. Polymorphism rs8192935 in the CES1 gene (p = 0.04), BMI (p = 0.01) and APTT level (p = 0.01) were statistically significant independent factors of trough plasma concentration of dabigatran. In contrast, polymorphisms rs4148738, rs1045642, rs2032582 and rs1128503 in ABCB1 and rs8192935, rs2244613 and rs71647871 CES1 genes did not show significant influence on plasma concentrations of dabigatran/apixaban drugs (p > 0.05). Patients with GG genotype (138.8 ± 100.1 ng/mL) had higher peak plasma concentration of dabigatran than with AA genotype (100.9 ± 59.6 ng/mL) and AG genotype (98.7 ± 72.3 ng/mL) (Kruskal-Wallis test, p = 0.25). Thus, CES1 rs8192935 is significantly associated with plasma concentrations of dabigatran in Kazakhstani NVAF patients (p < 0.05). The level of the plasma concentration shows that biotransformation of the dabigatran processed faster in individual carriers of GG genotype rs8192935 in the CES1 gene than with AA genotype.

Prognostic Value of Platelet-to-Lymphocyte Ratio Combined with CHA2DS2-VASc Score for Nonvalvular Atrial Fibrillation Induced Cardiogenic Cerebral Embolism.

Aim: To determine the predictive significance of the platelet-to-lymphocyte ratio (PLR) combined with the CHA2DS2-VASc score for cardiogenic cerebral embolism (CCE) in patients with nonvalvular atrial fibrillation (NVAF). Methods: A total of 553 patients with NVAF were included in this retrospective study. The general data, PLR, CHA2DS2-VASc score and echocardiography indicators were compared. The risk factors for CCE and the predictive value of PLR and CHA2DS2-VASc were analyzed. Stratified analysis was performed based on the cut-off value. Least absolute shrinkage and selection operator (LASSO) regression analysis was utilized to build a model. The relationship between risk score and different anticoagulants was evaluated. Results: Multiple regression analysis showed hypertension (OR=3.95, 95% CI=2.12-7.35, p=1.40×10-5), diabetes mellitus (OR=2.95, 95% CI=1.57-5.58, p=7.65×10-4), PLR (OR=1.01, 95% CI=1.00-1.01, p<10-6), creatinine level (OR=1.01, 95% CI=1.00-1.02, p=7.44×10-3), left atrial diameter (LAD) (OR=1.90, 95% CI=1.13-3.19, p=1.51×10-2), ejection fraction (EF) (OR=0.93, 95% CI=0.87-0.98, p=8.06×10-3) and CHA2DS2-VASc score (OR=3.79, 95% CI=2.95-4.85, p<10-6) were independent risk factors for CCE. A one-way linear analysis also showed the above seven indexes were significantly correlated with CCE (F=56.4, p<10-6). The area under the receiver operating characteristic (ROC) curve of PLR and CHA2DS2-VASc score was 0.760 (95% CI:0.721-0.800), and 0.855 (95% CI: 0.824-0.886), respectively. Pearson correlation analysis showed that PLR was correlated with CHA2DS2-VASc score (r=0.331, p<10-6). Stratified analysis indicated there was a positive correlation between different risk group (p<10-6). Using the LASSO model, a composite indicator displayed differential power for distinguishing CCE with an AUC value of 0.884 (95% CI: 0.857-0.911). Patients with dabigatran and rivaroxaban exhibited higher risk score than those with warfarin (warfarin vs dabigatran, p=1.40×10-2; warfarin vs rivaroxaban p=3.00×10-3). Conclusion: PLR and CHA2DS2-VASc score are independent risk factors for CCE with NVAF, and the combination of the two indices can improve the prediction of CCE.

Design and evaluation of oral formulation for apixaban.

Non-valvular atrial fibrillation (NVAF) is a common form of cardiac arrhythmia that affects 1-1.5% of adults and roughly 10% of elderly adults with dysphagia. Apixaban is an anticoagulant referred to as a factor Xa inhibitor, which has been shown to reduce the risk of stroke and systemic embolism in cases of NVAF. Our objective in the current study was to formulate an orally disintegrating film to facilitate the administration of apixaban to elderly patients who have difficulty swallowing. Researchers have used a wide variety of cellulose-based or non-cellulose-based polymers in a variety of combinations to achieve specific characteristics related to film formation, disintegration performance, drug content, in vitro drug release, and stability. One of the two formulations in this study was specify that bioequivalence criteria met with respect to Cmax of the reference drug (ELIQUIS®) in terms of pharmacokinetic profile. Further research will be required to assess the applicability of orodispersible films created using colloidal polymers of high and low molecular weights to other drugs with poor solubility in water.

Relationship between valvular structure and biochemical indices of non-valvular atrial fibrillation and senile degenerative valvular heart disease.

Background: Valvular heart disease (VHD) is a common clinical condition in geriatric-related cardiovascular diseases that is connected to heart dysfunction. Atrial fibrillation (AF) is the most frequent arrhythmia. Considering these two common clinical conditions, so far no sufficient data on the relationship between degenerative VHD and non-valvular atrial fibrillation (NVAF). We aimed to explore the relationship between valvular structure and biochemistry of nonvalvular AF and degenerative valvular heart disease in the elderly. Methods: In our study, 234 VHD patients who were diagnosis evaluated by transthoracic echocardiography were enrolled in this retrospective study from January 2015 and December 2018. Significant valvular diseases were defined according to ACC/AHA Classification as any moderate or severe mitral regurgitation (MR), aortic regurgitation (AR), tricuspid stenosis, regurgitation, or aortic stenosis (AS). Data on relevant laboratory indicators were also collected. Results: A total of 234 patients with degenerative VHD were enrolled, of whom 81 had NVAF and 153 had sinus rhythm. Gender, smoking history, and some comorbidities, such as coronary artery disease, diabetes, and renal dysfunction, did not differ significantly between the two groups, but there were significant differences in age and hypertension {79 [74-83] vs. 70 [65-79] years} After propensity-score matching (PSM), we identified 68 VHD patients with NVAF and 68 VHD patients without NVAF. The NVAF + VHD had higher low-density lipoprotein (LDL) cholesterol (2.94±0.84 vs. 2.26±1.33 mmol/L, P=0.001), lower high-density lipoprotein (HDL) cholesterol [1.03 (0.89-1.34) vs. 1.56 (0.99-2.71) mmol/L, P<0.001], and higher uric acid (UA) (438.18±145.83 vs. 376.67±148.03 µmol/L, P=0.02) than the VHD group. The ejection fraction (EF) of the NVAF + VHD group was lower than that of the VHD group {63 [51-68] vs. 66 [62-69], P=0.013}. In addition, the left atrial size, MR, and calcification of the NVAF + VHD group were higher than those of the VHD group. Conclusions: Pronounced MR, valve calcification and hyperlipidemia were more likely in VHD patients with NVAF. These structures and biomarkers changes maybe important clinical parameters for disease prevention and management, which indicate early drug intervention to AF and hyperlipidemia is necessary.

Cost-effectiveness of left atrial appendage closure with Watchman for non-valvular atrial fibrillation patients in Japan.

AIMS: Left atrial appendage closure (LAAC) has been demonstrated to be cost-saving relative to oral anticoagulants for stroke prophylaxis in patients with non-valvular atrial fibrillation (NVAF) in the United States and Europe. This study assessed the cost-effectiveness of LAAC with the Watchman device relative to warfarin and direct oral anticoagulants (DOACs) for stroke risk reduction in NVAF from a Japanese public healthcare payer perspective. METHODS: A Markov model was developed with 70-year-old patients using a lifetime time horizon. LAAC clinical inputs were from pooled, 5-year PROTECT AF and PREVAIL trials; warfarin and DOAC inputs were from published meta-analyses. Baseline stroke and bleeding risks were from the SALUTE trial on LAAC. Cost inputs were from the Japanese Medical Data Vision database. Probabilistic and one-way sensitivity analyses were performed. RESULTS: Over the lifetime time horizon, LAAC was less costly than warfarin (savings of JPY 1,878,335, equivalent to US $17,600) and DOACs (savings of JPY 1,198,096, equivalent to US $11,226). LAAC also provided 1.500 more incremental quality-adjusted life years (QALYs) than warfarin and 0.996 more than DOACs. In probabilistic sensitivity analysis, LAAC was cost-effective relative to warfarin and DOACs in 99.98% and 99.73% of simulations, respectively. LAAC dominated (had higher cumulative QALYs and was less costly than) warfarin and DOACs in 89.94% and 83.35% of simulations, respectively. CONCLUSIONS: Over a lifetime time horizon, LAAC is cost-saving relative to warfarin and DOACs for stroke risk reduction in NVAF patients in Japan and is associated with improved quality-of-life.

This study examined the cost-effectiveness of left atrial appendage closure (LAAC) compared to oral anticoagulants for stroke risk reduction among individuals with a specific type of irregular heart rhythm called non-valvular atrial fibrillation (NVAF). This study evaluated the cost-effectiveness of LAAC using the Watchman device in comparison to warfarin and direct oral anticoagulants (DOACs) from the perspective of Japan's public healthcare system. To investigate this, a computer-based model was developed involving 70-year-old patients over their lifetime. Data from notable studies such as the PROTECT AF and PREVAIL trials (covering 5 years) for LAAC and published meta-analyses for warfarin and DOACs were incorporated into the model. Baseline stroke and bleeding risks were derived from the SALUTE trial on LAAC. Cost inputs were based on data from the Japanese Medical Data Vision database. Additionally, we performed thorough cost-effectiveness analyses, including probabilistic and one-way sensitivity assessments. Our findings revealed that, over a lifetime, LAAC was more cost-effective than both warfarin and DOACs. Further, LAAC contributed an additional 1.500 quality-adjusted life years (QALYs) compared to warfarin and 0.996 QALYs compared to DOACs. In the long-term, adopting LAAC as an alternative to warfarin and DOACs is a cost-effective strategy for reducing stroke risk in NVAF patients in Japan. Moreover, it is associated with enhanced quality-of-life. These findings hold significant implications for informing decision-making in healthcare policies and clinical practices for NVAF patients.

Clinical features of ischemic stroke in patients with nonvalvular atrial fibrillation combined with intracranial atherosclerotic stenosis.

BACKGROUND: Nonvalvular atrial fibrillation (NVAF) and intracranial atherosclerotic stenosis (ICAS) are major causes of ischemic stroke. Relatively few studies have focused on the risk factors and clinical features of ischemic stroke caused by NVAF combined with ICAS. METHOD: We retrospectively evaluated NVAF and/or ICAS in patients with acute ischemic stroke admitted within 72 h after stroke. All patients with acute ischemic stroke underwent diffusion-weighted magnetic resonance imaging (DWI), magnetic resonance angiography (MRA), computed tomography angiography (CTA), and/or digital subtraction angiography (DSA). NVAF was detected by routine electrocardiogram or 24-h Holter examination, Doppler echocardiography, and contrast echocardiography of the right heart. RESULTS: Among the 635 enrolled patients, NVAF, ICAS, and NVAF+ICAS were diagnosed in 170 (26.77%), 255 (40.16%), and 210 (33.07%) patients, respectively. Patients in the NVAF+ICAS group were older (p < .001), specifically aged ≥75 years (p < .001). The admission time of the NVAF+ICAS group was shorter (p < .001) than that of the ICAS group. The admission NIHSS score of the NVAF group was higher than that of the NVAF+ICAS group (p < .001). HsCRP, NTpro-BNP, and LEVF levels were significantly different among the three groups (p < .001). NVAF+ICAS ischemic stroke occurred mainly in the right hemisphere (52.4%). CONCLUSION: NVAF with ICAS ischemic stroke is more likely to occur in older patients. Infarctions occurred mainly in the right cerebral hemisphere. Neurological deficits in NVAF are more severe than those in NVAF combined with ICAS and in simple ICAS ischemic strokes. HsCRP, LEVF, andNTpro-BNP seem to be closely associated with NVAF+ICAS ischemic stroke.

Exploring the Prognostic Performance of MECKI Score in Heart Failure Patients with Non-Valvular Atrial Fibrillation Treated with Edoxaban.

INTRODUCTION: Risk stratification in heart failure (HF) is essential for clinical and therapeutic management. The Metabolic Exercise test data combined with Cardiac and Kidney Indexes (MECKI) score is a validated prognostic model for assessing cardiovascular risk in HF patients with reduced ejection fraction (HFrEF). From the validation of the score, the prevalence of HF patients treated with direct oral anticoagulants (DOACs), such as edoxaban, for non-valvular atrial fibrillation (NVAF) has been increasing in recent years. This study aims to evaluate the reliability of the MECKI score in HFrEF patients treated with edoxaban for NVAF. MATERIALS AND METHODS: This study included consecutive outpatients with HF and NVAF treated with edoxaban (n = 83) who underwent a cardiopulmonary exercise test (CPET). They were matched by propensity score with a retrospective group of HFrEF patients with NVAF treated with vitamin K antagonists (VKAs) from the MECKI score registry (n = 844). The study endpoint was the risk of cardiovascular mortality, urgent heart transplantation, or Left Ventricle Assist Device (LVAD) implantation. RESULTS: Edoxaban patients were treated with a more optimized HF therapy and had different clinical characteristics, with a similar MECKI score. After propensity score, 77 patients treated with edoxaban were successfully matched with the MECKI-VKA control cohort. In both groups, MECKI accurately predicted the composite endpoint with similar area under the curves (AUC = 0.757 vs. 0.829 in the MECKI-VKA vs. edoxaban-treated group, respectively, p = 0.452). The two populations' survival appeared non-significantly different at the 2-year follow-up. CONCLUSIONS: this study confirms the prognostic accuracy of the MECKI score in HFrEF patients with NVAF treated with edoxaban, showing improved predictive power compared to VKA-treated patients.

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

BACKGROUND: Oral 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. METHODS: This 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. RESULTS: The 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. CONCLUSIONS: Over 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.