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The increasing burden of atrial fibrillation (AF) emphasizes the need to identify high-risk individuals for enrolment in clinical trials of AF screening and primary prevention. We aimed to develop prediction models to identify individuals at high-risk of AF across prediction horizons from 6-months to 10-years. We used secondary-care linked primary care electronic health record data from individuals aged ≥30 years without known AF in the UK Clinical Practice Research Datalink-GOLD dataset between January 2, 1998 and November 30, 2018; randomly divided into derivation (80%) and validation (20%) datasets. Models were derived using logistic regression from known AF risk factors for incident AF in prediction periods of 6 months, 1-year, 2-years, 5-years, and 10-years. Performance was evaluated using in the validation dataset with bootstrap validation with 200 samples, and compared against the CHA 2 DS 2 -VASc and C 2 HEST scores. Of 2,081,139 individuals in the cohort (1,664,911 in the development dataset, 416,228 in the validation dataset), the mean age was 49.9 (SD 15.4), 50.7% were women, and 86.7% were white. New cases of AF were 7,386 (0.4%) within 6 months, 15,349 (0.7%) in 1 year, 38,487 (1.8%) in 5 years, and 79,997 (3.8%) by 10 years. Valvular heart disease and heart failure were the strongest predictors, and association of hypertension with AF increased at longer prediction horizons. The optimal risk models incorporated age, sex, ethnicity, and 8 comorbidities. The models demonstrated good-to-excellent discrimination and strong calibration across prediction horizons (AUROC, 95%CI, calibration slope: 6-months, 0.803, 0.789-0.821, 0.952; 1-year, 0.807, 0.794-0.819, 0.962; 2-years, 0.815, 0.807-0.823, 0.973; 5-years, 0.807, 0.803-0.812, 1.000; 10-years 0.780, 0.777-0.784, 1.010), and superior to the CHA 2 DS 2 -VASc and C 2 HEST scores. The models are available as a web-based FIND-AF calculator. The FIND-AF models demonstrate high discrimination and calibration across short- and long-term prediction horizons in 2 million individuals. Their utility to inform trial enrolment and clinical decisions for AF screening and primary prevention requires further study. [Display omitted] [ABSTRACT FROM AUTHOR]

Objective: We aimed to evaluate the long-term risk of ischemic stroke/systemic embolism of hyperthyroidism-related AF.Methods: This retrospective population-based cohort study included records of 1,034,099 atrial fibrillation patients between 2005 and 2016 from the Korean National Health Insurance Service database. After exclusion, we identified 615,724 oral anticoagulation-naïve patients aged ≥18 years with new-onset non-valvular atrial fibrillation, of whom 20,773 had hyperthyroidism-related atrial fibrillation. After 3:1 propensity score matching, ischemic stroke and systemic embolism occurrences were compared between hyperthyroidism-related and non-hyperthyroidism-related ("nonthyroidal") atrial fibrillation patients.Results: After exclusion, we identified 615,724 oral anticoagulation-naïve AF patients of whom 20,773 had hyperthyroidism-related AF. Median follow-up duration was 5.9 years. Hyperthyroidism-related AF patients had significantly higher risks of ischemic stroke and systemic embolism than nonthyroidal AF patients (1.83 vs. 1.62 per 100-person year, hazard ratio[HR], 1.13; 95% confidence interval[CI], 1.07 to 1.19; P < 0.001). This risk was 36% higher in hyperthyroidism-related than in nonthyroidal AF patients within 1 year of atrial fibrillation diagnosis (3.65 vs. 2.67 per 100-person year, HR, 1.36; 95% CI, 1.24-1.50; P < 0.001). This difference was also observed in the CHA2DS2-VASc score subgroup analysis. The risk of ischemic stroke and systemic embolism significantly decreased in patients treated for hyperthyroidism (HR, 0.64; 95% CI, 0.58 to 0.70; P < 0.001).Conclusion: Hyperthyroidism-related AF patients have high risks of ischemic stroke and systemic embolism like nonthyroidal AF, especially when initially diagnosed. This risk is reduced by treating hyperthyroidism. [ABSTRACT FROM AUTHOR]

Background: Using cardiovascular magnetic resonance imaging (CMR), it is possible to detect diffuse fibrosis of the left ventricle (LV) in patients with atrial fibrillation (AF), which may be independently associated with recurrence of AF after ablation. By conducting CMR, clinical, electrophysiology and biomarker assessment we planned to investigate LV myocardial fibrosis in patients undergoing AF ablation. Methods: LV fibrosis was assessed by T1 mapping in 31 patients undergoing percutaneous ablation for AF. Galectin-3, coronary sinus type I collagen C terminal telopeptide (ICTP), and type III procollagen N terminal peptide were measured with ELISA. Comparison was made between groups above and below the median for LV extracellular volume fraction (ECV), followed by regression analysis. Results: On linear regression analysis LV ECV had significant associations with invasive left atrial pressure (Beta 0.49, P = 0.008) and coronary sinus ICTP (Beta 0.75, P < 0.001), which remained significant on multivariable regression. Conclusion: LV fibrosis in patients with AF is associated with left atrial pressure and invasively measured levels of ICTP turnover biomarker. [ABSTRACT FROM AUTHOR]

Endogenous fibrinolysis is a powerful natural defense mechanism against lasting arterial thrombotic occlusion. Recent prospective studies have shown that impaired endogenous fibrinolysis (or hypofibrinolysis) can be detected in a significant number of patients with acute coronary syndrome (ACS) using global assays and is a strong marker of future cardiovascular risk. This novel risk biomarker is independent of traditional cardiovascular risk factors and unaffected by antiplatelet therapy. Most prospective prognostic data have been obtained using a global assay using native whole blood at high shear or plasma turbidimetric assays, which are described herein. Tests of endogenous fibrinolysis could be used to identify patients with ACS who, despite antiplatelet therapy, remain at high cardiovascular risk. This review discusses the impact of currently available medications and those in development that favorably modulate fibrinolytic status and may offer a potential new avenue to improve outcomes in ACS. [ABSTRACT FROM AUTHOR]

Background: In the RE-DUAL PCI trial of patients with atrial fibrillation (AF) who underwent percutaneous coronary intervention (PCI), dabigatran dual therapy (110 or 150 mg bid, plus clopidogrel or ticagrelor) reduced International Society on Thrombosis and Haemostasis bleeding events compared with warfarin triple therapy, with noninferiority in overall thromboembolic events. This analysis assessed outcomes in relation to patient bleeding and stroke risk profiles, based on the modified HAS-BLED and CHA2DS2-VASc scores.Methods: The primary endpoint, major bleeding event (MBE) or clinically relevant nonmajor bleeding event (CRNMBE), was compared across study arms in patients categorized by modified HAS-BLED score 0-2 or ≥3. The composite endpoint of death, thromboembolic event, and unplanned revascularization rates was compared in patients categorized by CHA2DS2-VASc score 0-1, 2, or ≥3.Results: Risk of MBE or CRNMBE was lower with dabigatran dual therapy (both doses) versus warfarin triple therapy, irrespective of modified HAS-BLED category (treatment-by-subgroup interaction P-value 0.584 and 0.273 for dabigatran 110 and 150 mg dual therapy, respectively, vs warfarin). Risk of the composite thromboembolic endpoint was similar across CHA2DS2-VASc categories and consistent with overall study results (interaction P-value 0.739 and 0.075 for dabigatran 110 and 150 mg dual therapy, respectively, vs warfarin). Higher HAS-BLED scores were associated with higher risks of bleeding in AF patients after PCI in a treatment-independent analysis.Conclusion: Dabigatran dual therapy reduced bleeding events irrespective of bleeding risk category and demonstrated similar efficacy regardless of stroke risk category when compared with warfarin triple therapy. [ABSTRACT FROM AUTHOR]

Background: When assessing ischemic stroke risk in patients with atrial fibrillation (AF), the CHA2DS2-VASc score is calculated based on the baseline risk factors, and the outcomes are determined after a follow-up period. However, the stroke risk in patients with AF does not remain static, and with time, patients get older and accumulate more comorbidities.Objectives: This study hypothesized that the "Delta CHA2DS2-VASc score," which reflects the change in score between baseline and follow-up, would be more predictive of ischemic stroke compared with the baseline CHA2DS2-VASc score.Methods: A total of 31,039 patients with AF who did not receive antiplatelet agents or oral anticoagulants, and who did not have comorbidities of the CHA2DS2-VASc score except for age and sex, were studied. The Delta CHA2DS2-VASc scores were defined as the differences between the baseline and follow-up CHA2DS2-VASc scores. During 171,956 person-years, 4,103 patients experienced ischemic stroke. The accuracies of baseline, follow-up, and Delta CHA2DS2-VASc scores in predicting ischemic stroke were analyzed and compared.Results: The mean baseline CHA2DS2-VASc score was 1.29, which increased to 2.31 during the follow-up, with a mean Delta CHA2DS2-VASc score of 1.02. The CHA2DS2-VASc score remained unchanged in only 40.8% of patients. Among 4,103 patients who experienced ischemic stroke, 89.4% had a Delta CHA2DS2-VASc score ≥1 compared with only 54.6% in patients without ischemic stroke, and 2,643 (64.4%) patients had ≥1 new-onset comorbidity, the most common being hypertension. The Delta CHA2DS2-VASc score was a significant predictor of ischemic stroke that performed better than baseline or follow-up CHA2DS2-VASc scores, as assessed by the C-index and the net reclassification index.Conclusions: In this AF cohort, the authors demonstrated that the CHA2DS2-VASc score was not static, and that most patients with AF developed ≥1 new stroke risk factor before presentation with ischemic stroke. The Delta CHA2DS2-VASc score, reflecting the change in score between baseline and follow-up, was strongly predictive of ischemic stroke, reflecting how stroke risk in AF is a dynamic process due to increasing age and incident comorbidities. [ABSTRACT FROM AUTHOR]

Edoxaban-a non-vitamin K antagonist oral anticoagulant (NOAC)- 60-mg and 30-mg once-daily dose regimens are noninferior versus well-managed warfarin for the prevention of stroke or systemic embolic events (SEE) with less major bleeding in patients with nonvalvular atrial fibrillation (NVAF). There are no published data from phase 3 clinical trials specifically evaluating the use of NOACs in elderly NVAF patients, especially those considered ineligible for available oral anticoagulants. The Edoxaban Low-Dose for EldeR CARE AF patients (ELDERCARE-AF) study is a phase 3, randomized, double-blind, placebo-controlled, parallel-group, multicenter study that will compare the safety and efficacy of once-daily edoxaban 15 mg versus placebo in Japanese patients with NVAF ≥80 years of age who are considered ineligible for standard oral anticoagulant therapy. A total of 800 patients (400 in each treatment group) are planned for randomization (1:1) to either edoxaban or placebo using a stratified randomization method with CHADS2 index score (2 points, ≥3 points) as a factor. The primary efficacy end point is the time to first onset of stroke or SEE. The net clinical outcome is the composite of stroke, SEE, major bleeding, and all-cause mortality. The primary safety end point is the incidence of major bleeding. The treatment period will continue until 65 patients with the primary efficacy events (ie, stroke or SEE) have been observed (2- to 2.5-year expected mean treatment period). The results of ELDERCARE-AF may provide clarity as to the efficacy and safety of edoxaban for the prevention of stroke or SEE in this high-risk population. [ABSTRACT FROM AUTHOR]

Purpose Qualitative research on atrial fibrillation (AF) patient's experiences and perceptions of taking the non-vitamin K antagonist oral anticoagulants (NOACs) for stroke prevention is limited. This study explores patients' experiences of dabigatran and their recommendations for development of educational materials. Patients and methods Semi-structured individual interviews with 8 warfarin-naive and 8 warfarin-experienced AF patients, using qualitative deductive thematic analysis. Results The four main overarching themes included: understanding the diagnosis; reaching a treatment decision; challenges of living with OAC; and patient perceptions of treatment. Patients discussed their shock of diagnosis, and seeking information and support at that time. Narratives suggest patients preferred to be led by the doctor when making treatment decisions, and would often compare dabigatran to warfarin. Patients reported side-effects and challenges with both treatment options, and discussed their beliefs surrounding medications, including misconceptions. In addition to the original framework, two further themes were added: challenges of living with AF, and patient recommendations. Generally patients found AF symptoms distressing, which impacted their quality of life. Patient recommendations included the content and delivery of educational materials and development of tools to help with their understanding of AF and anticoagulation, as well as treatment adherence and anxiety surrounding symptoms and side effects. Conclusion Patient recommendations emphasised the need for interventions to relieve anxiety surrounding the diagnosis and possible treatment side effects. Tailored ‘disease-specific’ support is essential to ensure efficacious treatment. This qualitative study highlights the need for patient involvement in the development of educational materials and resources for patients commencing treatment with NOACs. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) confers increased risk of stroke and other thromboembolic events, and oral anticoagulation therefore is the essential part of AF management to reduce the risk of these complications. Until recently, the vitamin K antagonists (VKAs, e.g., warfarin) were the only oral anticoagulants available, acting by decreased synthesis of vitamin K-dependent coagulation factors (II, VI, IX, and X). The VKAs had many limitations: delayed onset and prolonged offset of action, variability of anticoagulant effect among patients, multiple food and drug interactions affecting pharmacological properties of warfarin, narrow therapeutic window, and obligatory regular laboratory control, which all made warfarin "inconvenient" both for patients and clinicians. The limitations of VKAs led to development of a new class of drugs collectively defined as non-VKA oral anticoagulants (NOACs), which included direct thrombin inhibitors (dabigatran) and factor Xa inhibitors (rivaroxaban, apixaban, and edoxaban). The NOACs avoid many of the VKA drawbacks. In this review, we will focus on the current evidence justifying the use of NOACs in non-valvular AF. [ABSTRACT FROM AUTHOR]

Non-vitamin K antagonist oral anticoagulants (NOACs) have changed the landscape for stroke prevention in atrial fibrillation (AF). Given the huge burden of AF in Asians, more attention to stroke prevention is clearly needed. Aiming to provide an overview and reappraisal of stroke prevention in Asians with AF, we searched MEDLINE for information on NOACs in Asians. In addition, abstracts from national and international cardiovascular meetings were studied to identify unpublished studies. In the 4 recent Phase 3 trials comparing NOACs to warfarin, a consistent pattern is evident. For efficacy endpoints in the comparison of NOACs vs warfarin, a significant reduction in stroke/systemic embolization was seen for dabigatran 150 mg [HR 0.45 (0.28-0.72)], with non-significant trends seen for lower stroke/systemic embolization with other NOACs, except edoxaban 30 mg. A similar pattern was seen for ischaemic stroke, with a significant reduction for dabigatran 150 mg [HR 0.55 (0.32-0.950]. For haemorrhagic stroke, all NOAC regimes, except rivaroxaban 20 mg, had significantly lower hazard ratios. No evidence of increased myocardial infarction was found for NOACs. All-cause mortality was significantly lowered amongst Asian patients on edoxaban 60 mg compared to warfarin [HR 0.63 (0.40-0.98)] with non-significant trends to lower mortality with dabigatran 150 mg, rivaroxaban and edoxaban 30 mg. For safety endpoints, all the NOAC regimes, except rivaroxaban 20 mg, significantly reduced major bleeding and 'all bleeding' events. Intracranial haemorrhage was consistently lowered by all NOACs. None of NOACs increased gastrointestinal bleeding. These information suggested that NOACs should be preferentially indicated for stroke prevention in Asians with AF. [ABSTRACT FROM AUTHOR]

Background Current risk schemes to predict ischemic stroke and intracranial hemorrhage (ICH) in atrial fibrillation (AF) are derived primarily using a Caucasian population. Objective The purpose of this study was to describe the risk of ischemic stroke and ICH in a large contemporary "real world" cohort of Chinese AF patients in Hong Kong with detailed long-term follow-up. Methods This observational study used a hospital-based cohort of Chinese patients with nonvalvular AF. Results Among 9727 patients with nonvalvular AF (age 76.9 ± 12.5 years, 52.1% female), 3881 patients (39.9%) did not receive antithrombotic therapy, 3934 patients (40.4%) were taking aspirin, and 1912 (19.7%) were taking warfarin. After mean follow-up of 3.19 years, 847 patients (21.8%) without antithrombotic therapy developed ischemic strokes (annual risk 9.28%, 95% confidence interval [CI] 8.89%-9.70%). There was a progressively increase in annual risk of ischemic stroke with increasing CHADS2 and CHA2DS2VASc scores. The c-statistics revealed that CHA2DS2-VASc scores (0.525, 95% CI 0.509-0.541, P = .017) was better than CHADS2 scores (0.506, 95% CI 0.490-0.522, P = .584) in predicting ischemic stroke. Use of aspirin and of warfarin were associated with reduced annual risk of ischemic stroke by 18.7% and 52.7%, respectively (P <.05). The annual incidence of ICH in patients taking aspirin and warfarin was 0.77% per year and 0.80% per year, respectively. The adjusted net clinical benefit favored warfarin over aspirin or no therapy for almost all Chinese AF patients CHA2DS2-VASc score ≥1. Conclusion Chinese AF patients are at high risk for ischemic stroke. Analysis of the net clinical benefit favors the use of warfarin over aspirin or no therapy for stroke prevention in a broad range of Chinese AF patients. [ABSTRACT FROM AUTHOR]

Background: Apixaban (5 mg BID), dabigatran (available as 150 mg and 110 mg BID in Europe), and rivaroxaban (20 mg once daily) are 3 novel oral anticoagulants (NOACs) currently approved for stroke prevention in patients with atrial fibrillation (AF). Objective: The objective of this study was to evaluate the cost-effectiveness of apixaban against other NOACs from the perspective of the United Kingdom National Health Services. Methods: A Markov model was developed to evaluate the pharmacoeconomic impact of apixaban versus other NOACs over a lifetime. Pair-wise indirect treatment comparisons were conducted against other NOACs by using ARISTOTLE (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation), RE-LY (Randomized Evaluation of Long-Term Anticoagulation Therapy), and ROCKET-AF (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared With Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation) trial results for the following end points: ischemic stroke, hemorrhagic stroke, intracranial hemorrhage, other major bleeds, clinically relevant nonmajor bleeds, myocardial infarction, and treatment discontinuations. Outcomes were life-years, quality-adjusted life years gained, direct health care costs, and incremental cost-effectiveness ratios. Results: Apixaban was projected to increase life expectancy versus other NOACs, including dabigatran (both doses) and rivaroxaban. A small increase in therapeutic management costs was observed with apixaban due to projected gains in life expectancy and lower discontinuation rates anticipated on apixaban versus other NOACs through lifetime. The estimated incremental cost-effectiveness ratio was £9611, £4497, and £5305 per quality-adjusted life-year gained with apixaban compared with dabigatran 150 mg BID, dabigatran 110 mg BID, and rivaroxaban 20 mg once daily, respectively. Sensitivity analyses indicated that results were robust over a wide range of inputs. Conclusions: Although our analysis was limited by the absence of head-to-head trials, based on the indirect comparison data available, our model projects that apixaban may be a cost-effective alternative to dabigatran 150 mg BID, dabigatran 110 mg BID, and rivaroxaban 20 mg once daily for stroke prevention in AF patients from the perspective of the United Kingdom National Health Services. [ABSTRACT FROM AUTHOR]

BACKGROUND AND METHODS: Abnormal circulating endothelial cell (CEC) and circulating progenitor cell (CPC) numbers are present in cancer, but their relationship with angiogenesis, apoptosis, vascular biology, and prognosis is unclear. We prospectively studied 160 patients with breast cancer and 63 age-matched controls free of breast cancer, measuring CECs (CD45-/CD146+/CD34+) and CPCs (CD45-/CD133+/CD34+) by flow cytometry and plasma markers of endothelial damage/dysfunction (von Willebrand factor), apoptosis (Fas/Fas-L) and angiogenesis (vascular endothelial growth factor [VEGF], angiogenin) by ELISA. These were compared with clinicopathophysiologic features and the Nottingham Prognostic Index (NPI). An additional blood sample was taken 6 to 8 weeks after surgery from 15 women to test the effect of tumor removal. RESULTS: CECs were significantly higher in the NPI poor prognostic group compared with moderate and good prognostic groups, and the cancer-free controls, whereas CPCs were lower in the poor prognosis group (both P < .05). Levels of von Willebrand factor, VEGF, angiogenin, and Fas-L (but not soluble Fas) were abnormal in breast cancer compared with controls (P < .05), with no relationship to prognosis groups. VEGF (P = .04) and angiogenin (P = .001) were markedly different after surgery. In multivariate analysis, vascular invasion (P < .05) and tumor size (P < .001) were independently associated with CECs. CPCs did not significantly associate with NPI in a linear regression model; age (P < .05) was a negative predictor, whereas Her-2 status (P < .05) positively predicted CPCs. After adjustment, no variable independently predicted CPC levels. CONCLUSIONS: CECs and CPCs demonstrate a strong relationship with NPI groups, but only CECs positively predict higher NPI scores and correlate with tumor invasiveness and size, possibly reflecting total tumor vascular volume. [ABSTRACT FROM AUTHOR]

In a multiethnic cohort of 388 patients admitted with symptomatic peripheral artery disease, atrial fibrillation was associated with emergency admission and increased mortality. Despite a greater prevalence of hypertension and diabetes in Afro-Caribbeans and diabetes in Indo-Asians, no significant differences were found in atrial fibrillation prevalence or mortality among different ethnic groups. Patients with symptomatic peripheral artery disease and atrial fibrillation should be regarded as “high risk” and managed with optimal medical therapy, including appropriate thromboprophylaxis and close follow-up. [Copyright &y& Elsevier]

We report a double-blind, multicenter, multinational, placebo-controlled, and well-controlled trial to prove that the sustained-release (SR) formulation of propafenone is superior to placebo in preventing symptoms of paroxysmal atrial fibrillation (AF). A total of 594 patients were enrolled in the qualifying period of the study and 293 patients were randomized at 53 centers. There were significant increases in the arrhythmia-free periods from day 5 of randomization to the first recurrence of symptomatic atrial arrhythmia in the propafenone SR 325 mg twice daily (p = 0.004) and propafenone SR 425 mg twice daily (p = 0.003) treatment groups compared with placebo. The median arrhythmia-free time was 9 days in the placebo group, 35 days in the propafenone SR 325 mg twice daily group, and 44 days in the propafenone SR 425 mg twice daily group. There was a significant reduction in average heart rate during the first recurrence of symptomatic arrhythmia after day 5 in the low-dose propafenone group compared with placebo. The median treatment failure time from day 5 (arrhythmia recurrence, adverse events, and withdrawals) was prolonged from 8 days in the placebo group to 19 days in the propafenone SR 325 mg twice daily group (p = 0.002) and to 24 days in the propafenone SR 425 mg twice daily group (p = 0.006). The percentage of patients with ≥1 serious adverse event was similar in the propafenone SR treatment groups (propafenone SR 325 mg twice daily, 10.0%; propafenone SR 425 mg twice daily, 11.2%) but lower in the placebo group (1.1%). In conclusion, the SR formulation of propafenone is superior to placebo, well-tolerated, and prevents symptoms of paroxysmal AF. [Copyright &y& Elsevier]

Background/objectives: Stroke-related visual impairment and atrial fibrillation are both common following stroke. This study explores whether presence of visual impairment following stroke is associated with presence of atrial fibrillation (AF).Subjects/methods: The Impact of Visual Impairment after Stroke (IVIS) study is a multi-centre, acute stroke unit, prospective epidemiology study. Standardised visual assessments included visual acuity, reading, visual fields, eye movements and visual perception. AF and blood pressure (BP) were measured on admission. Further data capture included stroke type, age, gender, stroke severity. Analysis included descriptive statistics, independent samples analysis and multivariate analysis for comparison of AF and visual impairment against covariates.Results: 1500 stroke admissions were recruited of which 1204 stroke survivors had visual assessment. New onset stroke-related visual impairment (n = 703) was significantly associated with older age and stoke severity. AF and BP data were available for 889 stroke survivors. AF was present on admission for 258 stroke survivors and significantly associated with older age, stroke severity and discharge destination. A significant association was found for presence of AF and presence of visual impairment. However, stroke severity was a contributing factor for this association. High systolic BP (>140 mmHg) was present in 62% and high diastolic BP (>90 mmHg) in 29%, but not associated with presence of visual impairment.Conclusions: AF and visual impairment, independently, occur commonly in stroke. Although our results show an association between AF and visual impairment, this appears to be independently influenced by stroke severity. AF was not associated with type of visual impairment or extent of visual recovery. It remains unknown if AF causes more severe visual impairment. [ABSTRACT FROM AUTHOR]

Background: Obesity and weight gain are established risk factors for atrial fibrillation (AF).Objective: The purpose of this study was to investigate whether bodyweight variability is also a risk factor for AF development.Methods: A nationwide population-based cohort of 8,091,401 adults from the Korean National Health Insurance Service database without a history of AF and with ≥3 measurements of bodyweight over a 5-year period were followed up for incident AF. Intraindividual bodyweight variability was calculated using variability independent of mean, and high bodyweight variability was defined as the quartile with the highest variability (Q4) with Q1-Q3 as reference.Results: During median 8.1 years of follow-up, each increase of 1 SD in bodyweight variability was associated with a 5% increased risk of AF development, and the quartile with the highest bodyweight variability showed 14% increased risk of AF development compared to the quartile with the lowest variability (hazard ratio 1.14; 95% confidence interval 1.12-1.15), after adjustment for baseline bodyweight, height, age, sex, lifestyle factors, and comorbidities. High bodyweight variability was significantly associated with AF development in all baseline body mass index (BMI) groups except the very obese (BMI ≥30), and this association was stronger in subjects with lower bodyweight. High bodyweight variability was associated with increased risk of incident AF in all weight change groups, with a stronger association in those who lost weight.Conclusion: Bodyweight fluctuation was independently associated with an increased risk of AF development, especially in individuals with low bodyweight, and regardless of weight gain or loss. [ABSTRACT FROM AUTHOR]

Background: Dual antiplatelet therapy (DAPT) with aspirin plus clopidogrel is used for stroke prevention in patients with atrial fibrillation (AF) who refuse to take use oral anticoagulants (OACs). However, clinical data comparing these treatments are limited.Objective: The purpose of this study was to compare the clinical outcomes between DAPT and OAC in patients with AF.Methods: A cohort study using a population-wide database of the Hong Kong Hospital Authority was performed. New patients with AF from 2010-2014 who were prescribed DAPT or OAC (warfarin or dabigatran) were followed until July 31, 2016. Outcomes were thromboembolism, bleeding, and death. Propensity score (PS) matching at a ratio of 1:2 was used to select DAPT users with characteristics similar to those of OAC users, analyzed using Poisson regression.Results: Among 51,946 new patients with AF, 8520 users of OAC and DAPT were identified. The likelihood of receiving DAPT over OAC increased with older age and previous intracranial hemorrhage. Among DAPT users, the incidences of thromboembolism, death, and bleeding per 100 patient-years were 15.8, 17.6, and 5.1, respectively. Compared to DAPT users, PS-matched analysis indicated a lower incidence of thromboembolism and/or death among OAC users (dabigatran: incidence rate ratio [IRR] 0.32; 95% confidence interval [CI] 0.19-0.55; warfarin: IRR 0.58; 95% CI 0.36-0.95), with no significant differences in bleeding events.Conclusion: DAPT users were at markedly increased risk for thromboembolism and death compared to OAC users. These findings indicate the need for improved stroke risk reduction strategies among patients taking DAPT and the opportunities for using OAC in high-risk groups to prevent additional events. [ABSTRACT FROM AUTHOR]

There are still many unresolved issues concerning patient outcomes and prognostic factors in patients with atrial fibrillation (AF) and left atrial/left atrial appendage (LA/LAA) thrombi. Rivaroxaban (Xarelto®), a potent and highly selective oral, direct factor Xa inhibitor, is a new therapeutic option in this setting. The planned study program will consist of a prospective interventional study (X-TRA) and a retrospective observational registry (CLOT-AF). The primary objective of the X-TRA study is to explore the efficacy of rivaroxaban in the treatment of LA/LAA thrombi in patients with nonvalvular AF or atrial flutter, scheduled to undergo cardioversion or AF ablation, in whom an LA/LAA thrombus has been found on transesophageal echocardiography (TEE) before the procedure. The primary end point is the complete LA/LAA thrombus resolution rate at 6 weeks of end of treatment confirmed by TEE. The secondary objectives are to describe categories of thrombus outcome in patients (resolved, reduced, unchanged, larger, or new) confirmed on TEE at the end of treatment (after 6 weeks of treatment), incidence of the composite of stroke and noncentral nervous system systemic embolism at the end of treatment and during follow-up, and incidence of all bleeding at the end of treatment and during follow-up. The objective of the CLOT-AF registry is to provide retrospective thrombus-related patient outcome data after standard-of-care anticoagulant treatment in patients with nonvalvular AF or atrial flutter, who have TEE-documented LA/LAA thrombi. The data will be used as a reference for the prospective X-TRA study. In conclusion, X-TRA and CLOT-AF will provide some answers to the many unresolved issues concerning patient outcomes and prognostic factors in patients with AF and LAA thrombi. Results from this study program would provide the first prospective interventional study (X-TRA) and a large international retrospective observational registry (CLOT-AF) on the prevalence and natural history of LA/LAA thrombi. Unique data on clot resolution with rivaroxaban in a prospective cohort would be obtained in X-TRA. [ABSTRACT FROM AUTHOR]

• Appropriate management of AF patients with cancer in real-world clinical practice is challenging. • In this EORP-AF study, we analyzed a cohort of AF patients with prior or active cancer. • A structured approach based on the "Atrial fibrillation Better Care" (ABC) Pathway is still suboptimal. • Adherence to the "C" criterion (i.e. management of comorbidities) was more critical, being specifically lower in cancer patients. • Adherence to the ABC pathway was independently associated with a lower risk outcomes. Implementation of the Atrial fibrillation Better Care (ABC) pathway is recommended by guidelines on atrial fibrillation (AF), but the impact of adherence to ABC pathway in patients with cancer is unknown. To investigate the adherence to ABC pathway and its impact on adverse outcomes in AF patients with cancer. Patients enrolled in the EORP-AF General Long-Term Registry were analyzed according to (i) No Cancer; and (ii) Prior or active cancer and stratified in relation to adherence to the ABC pathway. The composite Net Clinical Outcome (NCO) of all-cause death, major adverse cardiovascular events and major bleeding was the primary endpoint. Among 6550 patients (median age 69 years, females 40.1%), 6005 (91.7%) had no cancer, while 545 (8.3%) had a diagnosis of active or prior cancer at baseline, with the proportions of full adherence to ABC pathway of 30.6% and 25.7%, respectively. Adherence to the ABC pathway was associated with a significantly lower occurrence of the primary outcome vs. non-adherence, both in 'no cancer' and 'cancer' patients [adjusted Hazard Ratio (aHR) 0.78, 95% confidence interval (CI): 0.66–0.92 and aHR 0.59, 95% CI 0.37–0.96, respectively]. Adherence to a higher number of ABC criteria was associated with a lower risk of the primary outcome, being lowest when 3 ABC criteria were fulfilled (no cancer: aHR 0.54, 95%CI: 0.36–0.81; with cancer: aHR 0.32, 95% CI 0.13–0.78). In AF patients with cancer enrolled in the EORP-AF General Long-Term Registry, adherence to ABC pathway was sub-optimal. Full adherence to ABC-pathway was associated with a lower risk of adverse events [Display omitted] Adherence to the "Atrial fibrillation Better Care" (ABC) pathway in patients with atrial fibrillation and cancer and its impact on clinical outcomes. [ABSTRACT FROM AUTHOR]

We sought to assess the performance of existing bleeding risk scores, such as the Hypertension, Abnormal Renal/Liver Function, Stroke, Bleeding History or Predisposition, Labile INR, Elderly, Drugs/Alcohol Concomitantly (HAS-BLED) score or the Outpatient Bleeding Risk Index (OBRI), in patients with heart failure with reduced ejection fraction (HFrEF) in sinus rhythm (SR) treated with warfarin or aspirin. We calculated HAS-BLED and OBRI risk scores for 2,305 patients with HFrEF in SR enrolled in the Warfarin versus Aspirin in Reduced Cardiac Ejection Fraction trial. Proportional hazards models were used to test whether each score predicted major bleeding, and comparison of different risk scores was performed using Harell C-statistic and net reclassification improvement index. For the warfarin arm, both scores predicted bleeding risk, with OBRI having significantly greater C-statistic (0.72 vs 0.61; p = 0.03) compared to HAS-BLED, although the net reclassification improvement for comparing OBRI to HAS-BLED was not significant (0.32, 95% confidence interval [CI] -0.18 to 0.37). Performance of the OBRI and HAS-BLED risk scores was similar for the aspirin arm. For participants with OBRI scores of 0 to 1, warfarin compared with aspirin reduced ischemic stroke (hazard ratio [HR] 0.51, 95% CI 0.26 to 0.98, p = 0.042) without significantly increasing major bleeding (HR 1.24, 95% CI 0.66 to 2.30, p = 0.51). For those with OBRI score of =2, there was a trend for reduced ischemic stroke with warfarin compared to aspirin (HR 0.56, 95% CI 0.27 to 1.15, p = 0.12), but major bleeding was increased (HR 4.04, 95% CI 1.99 to 8.22, p <0.001). In conclusion, existing bleeding risk scores can identify bleeding risk in patients with HFrEF in SR and could be tested for potentially identifying patients with a favorable risk/benefit profile for antithrombotic therapy with warfarin. [ABSTRACT FROM AUTHOR]

Aims We assessed changes of serum combined free immunoglobulin light chains (cFLC) levels, which are associated with increased all-cause mortality, in ST-elevation myocardial infarction (STEMI) in relation to inflammation and renal function indices. Methods cFLC were measured in 48 patients with STEMI on days 1, 3, 7 and 30 with assessment of their relationships with monocyte subsets, high sensitivity C-reactive protein (hsCRP), and cystatin C. Day 1 levels in STEMI patients were compared to 40 patients with stable coronary artery disease, and 37 healthy controls. Results There were no significant differences in cFLC levels between the study groups. In STEMI patients, cFLC values peaked on day 7 post-MI and remained elevated on day 30 (p < 0.001 vs. day 1 for both). hsCRP concentrations peaked on day 3 of STEMI followed by their gradual reduction to the levels seen in the controls (p < 0.001). In STEMI cFLC correlated with cystatin C (r = 0.55, p < 0.001), and negatively correlated with counts of CD14++CD16- monocytes (r = -0.55, p < 0.001). On multivariate Cox regression analysis, cFLC concentrations were associated with increased need for future percutaneous coronary intervention (PCI) (p = 0.019). Conclusion cFLC levels increase during STEMI with peak values on day 7 after presentation and predict the need for future PCI. [ABSTRACT FROM AUTHOR]

Introduction The mental health prognosis following a venous thromboembolism in youth has not been investigated comprehensively. Using psychotropic drug purchase as a proxy for mental health status, we investigated this issue in a large cohort of young incident venous thromboembolism patients. Methods Using Danish nationwide administrative registries from the period 1997-2010, we identified 4,132 patients aged 13-33 years with a first-time venous thromboembolism diagnosis and no history of psychotropic drug usage. We sampled comparison cohort of random general population controls, matched individually in a 1:5 ratio based on sex and birth year. Participants were followed in prescription purchase registries for their first psychotropic drug purchase. Results Among young venous thromboembolism case cases, the 1-year risk of psychotropic drug purchase was 7.1% (95% confidence interval [CI] 6.3, 7.9) and the 5-year risk 22.1% (95% CI 20.7, 23.5). This was substantially higher than among population controls, with 1- and 5-year risk differences relative to the controls of 4.7% (95% CI 3.9, 5.5), and 10.8% (95% CI 9.4, 12.3), respectively. Adjustment for the effects of recent pregnancy or somatic provocations attenuated risk differences to 4.1% (95% CI 3.5, 5.1) after 1 year and 9.6% (95% CI 8.3, 11.2) after 5 years. Conclusions A venous thromboembolism diagnosis in youth is associated with a poorer mental health prognosis: one in five patients are prescribed psychotropic medication within the first 5 year after diagnosis. Highlights • VTE in the young is associated with a poor mental health prognosis • 1 in 5 patients purchase psychotropic drugs within 5 years after VTE diagnosis • Among similarly aged peers, only 1 in 10 purchase psychotropics in the same period • Young VTE patients may need long-term followup with a focus on mental health. [ABSTRACT FROM AUTHOR]

Background Current clinical guidelines recommend that risk stratification for ischaemic stroke in patients with nonvalvular AF (NVAF) should be performed using the CHA2DS2-VASc score (Congestive heart failure, Hypertension, Age ≥ 75 years [double], Diabetes mellitus, previous thromboembolism [double], Vascular disease, Age 65-74 years, and female gender) to aid decision making for antithrombotic treatment, with a preference for Non-Vitamin K Oral Anticoagulants (NOACs) in those with CHA2DS2-VASc score ≥ 1. However, CHA2DS2-VASc score is not recommended in the 2014 Japanese Circulation Society (JCS) guidelines for patients with NVAF. Methods To assess the impact of the JCS approach to stroke prevention in AF, and model the impact of using a CHA2DS2-VASc based 2-step decision making strategy, we calculated the incidence of ischaemic stroke in NVAF patients without OAC on basis of the CHADS2 and CHA2DS2-VASc scores using published Japanese data, and estimated the preventable number of stroke events. Results Using a CHA2DS2-VASc-based approach, the potential annual stroke events based on the estimated total number of NVAF patients in Japan was 889,000, as follows: 4369 for dabigatran 150 mg, 6049 for dabigatran 110 mg, 5918 for rivaroxaban (intention-to-treat; ITT), 5302 for apixaban, 5843 for edoxaban 60 mg (ITT), and 7598 for edoxaban 30 mg (ITT), respectively. Using a CHADS2 score-based approach, the number of potential stroke events was much greater for each agent. Conclusion Our modelling analysis has shown that when considering antithrombotic treatment for Japanese NVAF patients, using a CHA2DS2-VASc-based approach would allow greater opportunities for stroke prevention. [ABSTRACT FROM AUTHOR]

Describes the pathophysiology of the hypercoagulable state of cancer. Causes of prothrombotic state of malignancy; Prothrombotic factors in cancer; Information on tumor cells.

Most patients with atrial fibrillation (AF) and risk factors for stroke require oral anticoagulation (OAC) to decrease the risk of stroke or systemic embolism. This is now best achieved with direct oral anticoagulants that decrease the risk of intracranial bleeding compared with vitamin K antagonists. Of note, approximately 5% to 10% of patients undergoing percutaneous coronary intervention have AF, which complicates antithrombotic therapy in daily practice, because the guidelines recommend that these patients also receive dual antiplatelet therapy (DAPT) to reduce the risk of ischemic complications. However, combining OAC with DAPT, a strategy also known as triple antithrombotic therapy, is known to increase the risk of bleeding compared with the use of OAC or DAPT alone. Studies of direct oral anticoagulants are now emerging that show the favorable safety profile of double antithrombotic therapy with OAC and a P2Y12 inhibitor in comparison with triple antithrombotic therapy including the use of vitamin K antagonists. The scope of this review is to provide an update on this topic as well as to discuss future directions in the management of antithrombotic therapy after percutaneous coronary intervention in AF patients requiring chronic OAC. [ABSTRACT FROM AUTHOR]

Background: It is unclear whether the overall effectiveness and safety of direct oral anticoagulants (DOACs) are consistent in patients with nonvalvular atrial fibrillation (AF) and extremely low body weight (<50 kg).Objectives: This study compared DOACs with warfarin in AF patients with low body weight.Methods: Using data from the Korean National Health Insurance Service database from January 2014 to December 2016, AF patients with body weight ≤60 kg and who were treated with oral anticoagulants (n = 14,013 taking DOACs and n = 7,576 taking warfarin) were included and examined for ischemic stroke, intracranial hemorrhage (ICH), gastrointestinal bleeding, major bleeding, all-cause death, and composite outcome. The propensity score weighting was used to balance the 2 groups.Results: Baseline characteristics were well balanced between the 2 groups (mean age 73 years, mean CHA2DS2-VASc score 4, and 28% of patients weighed <50 kg). DOACs were associated with lower risks of ischemic stroke (hazard ratio [HR]: 0.591; 95% confidence interval [CI]: 0.510 to 0.686) and major bleeding (HR: 0.705; 95%: CI 0.601 to 0.825), which were caused by a reduction in ICH (HR: 0.554; 95% CI: 0.429 to 0.713) compared with warfarin. DOAC improved the net clinical benefit compared with warfarin (HR for composite outcome: 0.660; 95% CI: 0.606 to 0.717), and this was consistent in patients who weighed <50 kg (HR for composite outcome: 0.665; 95% CI: 0.581 to 0.762).Conclusions: In this real-world Asian AF population with low body weight, DOACs showed better effectiveness and safety than warfarin. These results were consistent in patients with extremely low body weight. Regular dosages of DOACs showed comparable results as reduced dosages of DOACs in both effectiveness and safety. [ABSTRACT FROM AUTHOR]

Background: It is unclear whether edoxaban shows better risk reduction of ischemic stroke, bleeding, and all-cause mortality than warfarin in Asian patients with nonvalvular atrial fibrillation (AF).Objectives: This study compared the effectiveness and safety of edoxaban with those of warfarin in a Korean population with AF.Methods: Using the Korean National Health Insurance Service database, we included new users of edoxaban and warfarin in patients with AF from January 2014 to December 2016 (n = 4,200 on edoxaban, and n = 31,565 on warfarin) and analyzed the risk of ischemic stroke, intracranial hemorrhage (ICH), hospitalization for gastrointestinal (GI) bleeding, hospitalization for major bleeding, and all-cause death. The propensity score matching method was used to balance covariates across edoxaban and warfarin users.Results: We compared a 1:3 propensity score-matched cohort of patients with AF who were new users of edoxaban and warfarin (n = 4,061 and n = 12,183, respectively). Baseline characteristics were balanced between the 2 groups (median age 72 years; median CHA2DS2-VASc [congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, prior stroke, transient ischemic attack, or thromboembolism, vascular disease, age 65-74 years, sex category (female)] score 3). Edoxaban users had a significantly lower risk of ischemic stroke (hazard ratio [HR]: 0.693; 95% confidence interval [CI]: 0.487 to 0.959), ICH (HR: 0.407; 95% CI: 0.182 to 0.785), hospitalization for GI bleeding (HR: 0.597; 95% CI: 0.363 to 0.930), hospitalization for major bleeding (HR: 0.532; 95% CI: 0.352 to 0.773), and all-cause death (HR: 0.716; 95% CI: 0.549 to 0.918) than warfarin users. All subgroups (age, sex, CHA2DS2-VASc score, renal function, edoxaban dose) showed better clinical outcomes with edoxaban than with warfarin.Conclusions: In this real-world Asian population with AF, edoxaban might be associated with reduced risk of ischemic stroke, major bleeding, and all-cause death compared with warfarin. These benefits were consistent across various high-risk subgroups. [ABSTRACT FROM AUTHOR]