Search

Evidence increasingly shows that the risk of thrombotic complications in COVID-19 is associated with a hypercoagulable state. Several organizations have released guidelines for the management of COVID-19-related coagulopathy and prevention of VTE. However, an urgent need exists for practical guidance on the management of arterial thrombosis and thromboembolism in this setting. What is the current available evidence informing the prevention and management of arterial thrombosis and thromboembolism in patients with COVID-19? A group of approved panelists developed key clinical questions by using the Population, Intervention, Comparator, and Outcome (PICO) format that address urgent clinical questions regarding prevention and management of arterial thrombosis and thromboembolism in patients with COVID-19. Using MEDLINE via PubMed, a literature search was conducted and references were screened for inclusion. Data from included studies were summarized and reviewed by the panel. Consensus for the direction and strength of recommendations was achieved using a modified Delphi survey. The review and analysis of the literature based on 11 PICO questions resulted in 11 recommendations. Overall, a low quality of evidence specific to the population with COVID-19 was found. Consequently, many of the recommendations were based on indirect evidence and prior guidelines in similar populations without COVID-19. The existing evidence and panel consensus do not suggest a major departure from the management of arterial thrombosis according to recommendations predating the COVID-19 pandemic. Data on the optimal strategies for prevention and management of arterial thrombosis and thromboembolism in patients with COVID-19 are sparse. More high-quality evidence is needed to inform management strategies in these patients. [ABSTRACT FROM AUTHOR]

• This is the largest study of dabigatran use during cardiovascular interventions in clinical practice from prospectively collected data. • Two thirds of the interventions were performed with uninterrupted dabigatran therapy, of which the majority included AF-cardioversions. • Continuation of dabigatran therapy during cardiovascular interventions was associated with low risk of major bleeding and stroke/systemic embolism. Prospective data on nonvitamin-K-antagonist oral anticoagulant (NOAC) management during cardiovascular interventions are limited. We therefore evaluated the safety and effectiveness of uninterrupted dabigatran therapy as well as dabigatran management during atrial fibrillation (AF)-cardioversions, AF-ablations, pacemaker implantations and coronary angiography and/or stenting procedures. GLORIA-AF is an international registry programme involving patients with newly diagnosed AF. Dabigatran users were followed for ≤2 years. The primary outcome was occurrence of stroke/systemic embolism and major bleeding ≤8 weeks after a cardiovascular intervention during uninterrupted dabigatran therapy. During the 2-year follow-up, 599 cardiovascular interventions were identified in 479 eligible patients. 412/599 (69%) interventions were performed with uninterrupted dabigatran therapy: 299/354 (84%) AF-cardioversions, 38/89 (43%) AF-ablations, 25/58 (43%) pacemaker implantations, and 50/98 (51%) coronary angiography and/or stenting procedures. During an average follow-up of 8.4 weeks after intervention, one major bleed and one systemic embolic event occurred (risk 0.25% for both outcomes; 95% confidence interval, 0.01%-1.36%). More than two thirds of the interventions were performed with uninterrupted dabigatran therapy, of which most were AF-cardioversions. Uninterrupted dabigatran therapy was associated with low major bleeding and stroke/systemic embolism risk, supporting the favourable safety and effectiveness profile of dabigatran in clinical practice-based settings. [ABSTRACT FROM AUTHOR]

Patients with cirrhosis are not only at an increased risk of bleeding but also at risk of venous thromboembolism (VTE). We sought to determine the clinical characteristics, management, and outcomes after VTE in patients with cirrhosis. We used the data from RIETE (Registro Informatizado de la Enfermedad TromboEmbolica), an international registry of patients with VTE, to compare the outcomes in patients with and without cirrhosis. Main outcomes included all-cause mortality, pulmonary embolism (PE)-related mortality, recurrent VTE, and bleeding. Among 43,611 patients with acute VTE, 187 (0.4%) had cirrhosis. Of these, 184 (98.4%) received anticoagulation for a median of 109 days (interquartile range [IQR]: 43–201 days), most commonly with enoxaparin (median dose: 1.77 [IQR: 1.38–2.00] mg/kg/day). Compared with patients without cirrhosis, those with cirrhosis had a higher rate of all-cause mortality (10.7 vs. 3.4%; odds ratio [OR]: 3.41; 95% confidence interval [CI]: 2.03–5.46) and fatal bleeding (2.1 vs. 0.2%; OR: 13.94; 95% CI: 3.65–37.90) but similar rates of fatal PE (0.5 vs. 0.5%; OR: 1.17; 95% CI: 0.03–6.70). Patients with cirrhosis had a higher rate of all-cause mortality per 100 patient-years of follow-up (58.9 vs. 16.0; hazard ratio [HR]: 3.70; 95% CI: 2.69–4.91). One-year hazard ratio of clinically relevant bleeding (HR: 2.86; 95% CI: 1.91–4.27), fatal bleeding (HR: 8.51; 95% CI: 3.5–20.7), or recurrent VTE (HR: 2.08; 95% CI: 1.00–4.36) was higher in patients with cirrhosis. Cirrhosis is a challenging comorbidity in patients with VTE. Most patients were treated with anticoagulation and had an elevated risk of recurrence, similar risk of fatal PE, and a very high risk of bleeding including fatal bleeds. [ABSTRACT FROM AUTHOR]

Background: The long-term risks of thromboembolism and mortality are unknown in patients who survived following atrial fibrillation (AF) newly diagnosed during critical care.Methods: Using the Korean National Health Insurance Service database, we identified 30,869 adults who survived for > 6 months following AF newly diagnosed during critical care (ICU-AF), 269,751 control subjects with non-ICU AF (AF-control), and 439,868 control subjects without AF (No-AF) from 2005 to 2013. We performed propensity score matching and compared the risks of stroke/systemic embolism and all-cause mortality.Results: The adjusted hazard ratios (HRs) for long-term stroke/systemic embolism in the patients with ICU-AF were 0.93 (95% CI, 0.88-0.98) compared with the AF-control group and 1.50 (95% CI, 1.42-1.60) compared with the No-AF group. The adjusted HRs of the ICU-AF group for long-term mortality were 1.73 (95% CI, 1.70-1.83) and 3.20 (95% CI, 3.08-3.33) compared with the AF-control and No-AF groups, respectively. The risks of stroke/systemic embolism and mortality were significantly higher in the ICU-AF group than in the No-AF group after excluding patients with AF recurrence (adjusted HR, 1.08; 95% CI, 1.01-1.17), regardless of the causes of critical care and cardiovascular or noncardiovascular surgery.Conclusions: The patients who survived following AF newly diagnosed during critical care remained at a higher risk of long-term stroke/systemic embolism and mortality than the patients without AF regardless of AF recurrence and the causes of critical care. Close follow-up and continuous anticoagulation might be needed for these patients. [ABSTRACT FROM AUTHOR]

Background: Whether four direct oral anticoagulants (DOACs) are superior to warfarin in Asian patients with nonvalvular atrial fibrillation (NVAF) remains unclear.Methods: This nationwide retrospective cohort study was based on data from Taiwan's National Health Insurance Research Database from June 1, 2012, to December 31, 2017, covering patients with NVAF taking edoxaban (n = 4,577), apixaban (n = 9,952), rivaroxaban (n = 33,022), dabigatran (n = 22,371), and warfarin (n = 19,761). Propensity score weighting was used to balance covariates across study groups. Patients were followed up until occurrence of study outcomes or end date of study.Results: Edoxaban, apixaban, and rivaroxaban were associated with a lower risk of ischemic stroke/systemic embolism than warfarin. All DOACs had a lower risk of major bleeding than warfarin. Apixaban was associated with a lower risk of major bleeding than rivaroxaban and dabigatran, whereas the risk of major bleeding was comparable between edoxaban and apixaban. The reduced risks of thromboembolism/major bleeding for the four DOACs persisted in high-risk subgroups, including those with chronic kidney disease, elderly patients (age ≥ 75 years), secondary stroke prevention, or CHA2DS2-VASc score (congestive heart failure, hypertension, age ≥ 75 years, diabetes mellitus, previous stroke/transient ischemic attack, vascular disease, age 65-74 years, and female sex) ≥ 4. A total of 2,924 (64%), 6,359 (64%), 31,108 (94%), and 19,821 (89%) patients received low-dose edoxaban (15-30 mg/d), apixaban (2.5 mg bid), rivaroxaban (10-15 mg/d), and dabigatran (110 mg bid), respectively. The effectiveness/safety outcomes with the four low-dose DOACs compared with warfarin were consistent with the main analysis.Conclusions: In the largest real-world practice study among Asian patients with NVAF, four DOACs were associated with a comparable or lower risk of thromboembolism, and a lower risk of bleeding than warfarin. There was consistency even among high-risk subgroups and whether standard-or low-dose regimens were compared. [ABSTRACT FROM AUTHOR]

• Pulmonary embolism (PE) patients who are low risk benefit from early discharge. • A machine learning model is developed to predict short and long term mortality in PE. • This model improved on standard clinical risk stratification for PE patients. • External validation is required to determine generalizability of the model. Pulmonary embolism (PE) is a severe condition that causes significant mortality and morbidity. Due to its acute nature, scores have been developed to stratify patients at high risk of 30-day mortality. Here we develop a machine-learning based score to predict 30-day, 90-day, and 365-day mortality in PE patients. The Birmingham and Black Country Venous Thromboembolism registry (BBC-VTE) of 2183 venous thromboembolism patients is used. Random forests were trained on a 70% training cohort and tested against 30% held-out set. The outcomes of interest were 30-day, 90-day, and 365-day mortality. These were compared to the pulmonary embolism severity index (PESI) and simplified pulmonary embolism severity index (sPESI). Shapley values were used to determine important predictors. Oral anticoagulation at discharge was also investigated as a predictor of mortality. The machine learning risk score predicted 30-day mortality with AUC 0.71 [95% CI: 0.63 - 0.78] compared to the sPESI AUC of 0.65 [95% CI: 0.57 - 0.73] and PESI AUC of 0.64 [95% CI: 0.56 – 0.72]. 90-day mortality and 365-day mortality were predicted with an AUC of 0.74 and 0.73 respectively. High counts of neutrophils, white blood cell counts, and c-reactive protein and low counts of haemoglobin were important for 30-day mortality prediction but progressively lost importance with time. Older age was an important predictor of high risk throughout. Machine learning algorithms have improved on standard clinical risk stratification for PE patients. External cohort validation is required before incorporation into clinical workflows. [ABSTRACT FROM AUTHOR]

The article reports on short-term outcomes of apixaban versus warfarin in patients with atrial fibrillation (AF). It is opined that apixaban is safe in extremes of body weight and it appears superior to warfarin in both low- and high-weight individuals. It also presents a post hoc analysis of the ROCKET-AF trial (Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in AF).

The article presents a case study of a Patients with atrial fibrillation (AF), at high risk of thrombus formation, in the left atrium (LA) and left atrial appendage (LAA), leading to stroke and systemic embolism. It mentions the distribution of clinical and demographic characteristics among patients with and without left atrial thrombus (LAT); and examines the resolution rate after 6weeks treatment was 41.5 percent and resolved or reduced thrombus was identified in 60.4 percent of patients.

Background: The benefits and harms of oral anticoagulation therapy in patients with only one stroke risk factor (ie, CHA2DS2-VASc = 1 in males, or 2 in females) has been a subject of debate.Methods: We analyzed all patients with only one stroke risk factor from the merged datasets of SPORTIF III and V trials. Anticoagulation control was defined according to time in therapeutic range (TTR).Results: Of the original trial cohort, 1097 patients had only one stroke risk factor. Stroke/systemic thromboembolic event had an incidence of 0.9 per 100 patient-years, with an incidence of 1.6 per 100 patient-years for all-cause death and 2.3%/patient-years for the composite outcome of stroke/systemic thromboembolic event/all-cause death. There were no significant differences in the risk for stroke/systemic thromboembolic event between sexes, nor between the different stroke risk factors amongst these atrial fibrillation patients with only one stroke risk factor. Cox regression analysis in patients treated with warfarin found only TTR to be inversely associated with stroke/systemic thromboembolic event (P = .034) and all-cause death (P = .015). Chronic heart failure was significantly associated with the outcome of all-cause death (P = .0019) and the composite outcome of stroke/systemic thromboembolic event/all-cause death (P = .021). There was a significant inverse linear association between TTR and the cumulative risk for both stroke/systemic thromboembolic event and all-cause death (both P <.001).Conclusions: In atrial fibrillation patients with only one additional stroke risk factor (ie, CHA2DS2-VASc = 1 in males or 2 in females), rates of major adverse events (stroke/systemic thromboembolic event, mortality) were high, despite anticoagulation. TTR in warfarin-treated patients was inversely associated with the occurrence of both stroke/systemic thromboembolic event and all-cause death. [ABSTRACT FROM AUTHOR]

Background Even a single additional stroke risk factor in patients with atrial fibrillation may confer a risk of stroke. However, there is no consensus on how best to treat these patients. Objectives Our objective was to investigate the risk of stroke and bleeding and the impact of antithrombotic therapy among low-risk patients, i.e., with 0 or 1 CHA 2 DS 2 -VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke/transient ischemic attack, vascular disease, age 65 to 74 years, sex category) score risk factor. Methods The nationwide cohort for this study was established by linking data from the Danish Civil Registration System, the Danish National Patient Register, and the Danish National Prescription Registry. We studied 39,400 patients discharged with incident nonvalvular atrial fibrillation with 0 or 1 CHA 2 DS 2 -VASc risk factor; 23,572 were not treated, 5,353 were initiated on aspirin, and 10,475 were initiated on warfarin. Results Stroke event rates for untreated low-risk patients (CHA 2 DS 2 -VASc = 0 [male], 1 [female]) were 0.49 per 100 person-years at 1 year and 0.47 per 100 person-years at full follow-up (intention-to-treat). Bleeding event rates among untreated low-risk patients were 1.08 per 100 person-years at 1 year and 0.97 at full follow-up. The presence of 1 additional stroke risk factor (CHA 2 DS 2 -VASc = 1 [male], = 2 [female]) among untreated patients increased the stroke rate at 1 year to 1.55 per 100 person-years, representing a significant 3.01-fold increase. At the 1-year follow-up, bleeding increased 2.35-fold, and death increased 3.12-fold. Conclusions Low-risk patients (CHA 2 DS 2 -VASc = 0 [male], 1 [female]) have a truly low risk for stroke and bleeding. With 1 additional stroke risk factor (CHA 2 DS 2 -VASc = 1 [male], = 2 [female]), there was a significant increase in event rates (particularly mortality) if nonanticoagulated. [ABSTRACT FROM AUTHOR]

Background Thromboembolic complications remain one of the most severe adverse events associated with catheter ablation of atrial fibrillation (AF), but data on such events are limited. Objective The purpose of this study was to evaluate the incidence, characteristics, and risk factors of thromboembolic complications after AF ablation. Methods Cerebral thromboembolic complications occurring within 1 month of 3360 consecutive AF radiofrequency catheter ablations were assessed. Stroke was defined as a neurologic deficit lasting more than 24 hours or with imaging study showing new infarction. Transient ischemic attack (TIA) was defined as a deficit lasting less than 24 hours and without documented infarction. Results There were 17 peri-interventional cerebral thromboembolic events (0.5%). Nine cases (53%) were diagnosed as strokes and 8 (47%) as TIAs. Sixty percent of the events occurred within 48 hours after the ablation; the rest occurred within 1 week. In univariate analysis, peri-interventional thromboembolism was associated with peripheral vascular disease ( P = .010), impaired left ventricular ejection fraction ( P = .040), periprocedural bridging with heparin ( P = .007), and previous stroke ( P = .026). Multivariable analysis demonstrated that peripheral vascular disease (odds ratio [OR] 8.81, confidence interval [CI] 1.61–48.31, P = .012) and previous stroke (OR 6.13, CI 1.18–31.91, P = .031) were independent predictors. In a different model, the CHA 2 DS 2 -VASc score was associated with thromboembolism (OR 1.35, CI 1.00–1.80, P = .049). Conclusion Cerebral thromboembolic complications after AF radiofrequency catheter ablation are rare. They mostly occur within 48 hours after the procedure and remain without lasting neurologic deficits in the majority of cases. Such complications are associated with peripheral vascular disease, previous stroke, and the CHA 2 DS 2 -VASc score. [ABSTRACT FROM AUTHOR]

Background: There is growing evidence that chemokines are potentially important mediators of the pathogenesis of atherosclerotic disease. Major atherothrombotic complications, such as stroke and myocardial infarction, are common among atrial fibrillation (AF) patients. This increase in risk of adverse events may be predicted by a score based on the presence of certain clinical features of chronic heart failure, hypertension, age 75 years or greater, diabetes and stroke (the CHADS2 score). Our objective was to assess the prognostic value of plasma chemokines CCL2, CXCL4 and CX3CL1, and their relationship with the CHADS2 score, in AF patients. Methods: Plasma CCL2, CXCL4 and CX3CL1 were measured in 441 patients (59% male, mean age 75 years, 12% paroxysmal, 99% on warfarin) with AF. Baseline clinical and demographic factors were used to define each subject's CHADS2 score. Patients were followed up for a mean 2.1 years, and major adverse cardiovascular and cerebrovascular events (MACCE) were sought, being the combination of cardiovascular death, acute coronary events, stroke and systemic embolism. Results: Fifty-five of the AF patients suffered a MACCE (6% per year). Those in the lowest CX3CL1 quartile (≤0.24 ng/ml) had fewest MACCE (p = 0.02). In the Cox regression analysis, CX3CL1 levels >0.24 ng/ml (Hazard ratio 2.8, 95% CI 1.02-8.2, p = 0.045) and age (p = 0.042) were independently linked with adverse outcomes. The CX3CL1 levels rose directly with the CHADS2 risk score (p = 0.009). The addition of CX3CL1 did not significantly increased the discriminatory ability of the CHADS2 clinical factor-based risk stratification (c-index 0.60 for CHADS2 alone versus 0.67 for CHADS2 plus CX3CL1 >0.24 ng/ml, p = 0.1). Aspirin use was associated with lower levels of CX3CL1 (p = 0.0002) and diabetes with higher levels (p = 0.031). There was no association between CXCL4 and CCL2 plasma levels and outcomes. Conclusion: There is an independent association between low plasma CX3CL1 levels and low risk of major cardiovascular events in AF patients, as well as a linear association between CX3CL1 plasma levels and CHADS2-defined cardiovascular risk. The potential for CX3CL1 in refining risk stratification in AF patients merits consideration. © 2014 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Abstract: Background: In patients at high risk of stroke, such as atrial fibrillation (AF), there has been great interest in developing stroke risk prediction schemes for identifying those at high risk of stroke. Stroke risk prediction schemes have also been developed in non-AF populations, but are limited by lack of simplicity, which is more evident in schemes used in AF populations. We hypothesized that contemporary stroke risk stratification schemes used in assessing AF patients could predict stroke and thromboembolism in a non-AF community population, comparably to that seen in AF populations. Methods: We tested the CHADS2 and CHA2DS2-VASc schemes, as well as the AF stroke risk stratification schemes from the Framingham study, Rietbrock et al., 2006 ACC/AHA/ESC guidelines, the 8th American College of Cardiology (ACCP) guidelines and NICE, for predicting stroke in a large community cohort of non-AF subjects, the Chin-Shan Community Cohort Study. Results: The tested schemes had variable classification into low, moderate and high risk strata, with the proportion classified as low risk ranging from 5.4% (Rietbrock et al. to 59.0% (CHADS2 classical). Rates of stroke also varied in those classified as ‘low risk’ ranging from 1.1% (Rietbrock et al. to 3.5% (Framingham). All common risk schemes had broadly similar c-statistics, ranging from 0.658 (Framingham) to 0.728 (CHADS2 classical) when assessed as a continuous risk variable for predicting stroke in this population, with clear overlap between the 95% CIs. In an exploratory analysis amongst AF subjects in our population, the c-statistics were broadly similar to those seen in non-AF subjects. Conclusion: Contemporary stroke risk stratification schema used for AF can also be applied to non-AF populations with a similar (modest) predictive value. Given their simplicity (e.g. CHADS2 score), these scores could potentially be used for a ‘quick’ evaluation of stroke risk in non-AF populations, in a similar manner to AF populations. [Copyright &y& Elsevier]

Background: Both atrial fibrillation and chronic kidney disease increase the risk of stroke and systemic thromboembolism. However, these risks, and the effects of antithrombotic treatment, have not been thoroughly investigated in patients with both conditions. Methods: Using Danish national registries, we identified all patients discharged from the hospital with a diagnosis of nonvalvular atrial fibrillation between 1997 and 2008. The risk of stroke or systemic thromboembolism and bleeding associated with non–end-stage chronic kidney disease and with end-stage chronic kidney disease (i.e., disease requiring renal-replacement therapy) was estimated with the use of time-dependent Cox regression analyses. In addition, the effects of treatment with warfarin, aspirin, or both in patients with chronic kidney disease were compared with the effects in patients with no renal disease. Results: Of 132,372 patients included in the analysis, 3587 (2.7%) had non–end-stage chronic kidney disease and 901 (0.7%) required renal-replacement therapy at the time of inclusion. As compared with patients who did not have renal disease, patients with non–end-stage chronic kidney disease had an increased risk of stroke or systemic thromboembolism (hazard ratio, 1.49; 95% confidence interval [CI], 1.38 to 1.59; P<0.001), as did those requiring renal-replacement therapy (hazard ratio, 1.83; 95% CI, 1.57 to 2.14; P<0.001); this risk was significantly decreased for both groups of patients with warfarin but not with aspirin. The risk of bleeding was also increased among patients who had non–end-stage chronic kidney disease or required renal-replacement therapy and was further increased with warfarin, aspirin, or both. Conclusions: Chronic kidney disease was associated with an increased risk of stroke or systemic thromboembolism and bleeding among patients with atrial fibrillation. Warfarin treatment was associated with a decreased risk of stroke or systemic thromboembolism among patients with chronic kidney disease, whereas warfarin and aspirin were associated with an increased risk of bleeding. (Funded by the Lundbeck Foundation.) [ABSTRACT FROM PUBLISHER]

The article presents a study that tested the predictive ability of three stratification schemes including van Walraven risk stratification schemes in a cohort of lone atrial fibrillation (AF) patients. The study focused on 345 patients initially diagnosed with lone AF between 1992 and 2007. The schema identified the lone AF patients who were at truly low risk for thromboembolism.

AF Treatment Strategies. Introduction: The Atrial Fibrillation (AF) Exchange Group, an international multidisciplinary group concerned with the management of AF, was convened to review recent advances in the field and the potential impact on treatment strategies. Methods: Issues discussed included epidemiology and the impact of the rising incidence of AF on health care systems, developments in pharmacological and surgical interventions in the management of arrhythmias and thromboprophylaxis, the potential to affect treatment strategies, and barriers to implementing them. Results: The incidence of AF and the associated burden on health care systems are increasing with aging populations, prevalence of comorbidities and more effective treatment of cardiovascular diseases. Advances in available medical treatments, in particular dronedarone and dabigatran, with other products in development, offer the possibility of changes in treatment paradigms and a greater emphasis on reducing hospitalizations and improvement in long-term outcomes instead of a symptom/safety-driven approach in which the priority is symptom suppression without provoking drug toxicity. Developments in catheter ablation techniques may mean that, in experienced centers, ablation may be offered as first-line treatment in selected patient populations. Barriers to optimal treatment include underdiagnosis, lack of recognition as a serious condition and as a risk factor for stroke, limited access to care, inadequate implementation of guidelines, and poor adherence to treatment. Conclusions: The focus of the management of AF may be changing as a consequence of new treatments based on the outcome improvements they offer. However, the benefits will not be fully realized if guidelines and guidance are not observed in routine clinical practice. (J Cardiovasc Electrophysiol, Vol. 21, pp. 946-958, August 2010) [ABSTRACT FROM AUTHOR]

Abstract: Patients with heart failure (HF) are at an increased risk of stroke, sudden death and venous thromboembolism, which are all linked to thrombus formation (thrombogenesis). The present ‘viewpoint’ article will discuss how the prothrombotic state in HF may be perpetuated by a chronic inflammatory state that is maladaptive. Indeed, there is considerable evidence that thrombogenesis and endothelial (dys)function can be intimately linked to inflammation in HF. [Copyright &y& Elsevier]

As the most prevalent form of arrhythmia, atrial fibrillation (AF) increases the risk of heart failure, thromboembolism, and stroke, contributing to the raising mortality and morbidity in patients with cardiovascular diseases. Despite the multifaceted nature of AF pathogenesis and complexity of AF pathophysiology, a growing body of evidence indicates that the NLRP3 inflammasome activation contributes to onset and progression of AF. Herein, the authors aim at reviewing the current literature on the role of inflammasome signaling in AF pathogenesis, and novel therapeutic options in the management of AF. [ABSTRACT FROM AUTHOR]

Background Diabetes mellitus is associated with increased risk of stroke in patients with atrial fibrillation, and differences in glycemic status may affect this risk. We aimed to examine the effect of glycemic status evaluated by hemoglobin A1c (HbA1c) on the risk of thromboembolism among patients with atrial fibrillation and type 2 diabetes mellitus. Methods In this cohort study, we used data from Danish registries to identify patients with type 2 diabetes mellitus and incident nonvalvular atrial fibrillation in the period of May 1, 2005, through December 31, 2015. On the basis of the most recent HbA1c measurement before an incident atrial fibrillation diagnosis, patients were divided into the categories: HbA1c ≤48 mmol/mol, HbA1c=49-58 mmol/mol, and HbA1c >58 mmol/mol. Cox regression analysis was used to estimate hazard ratios for the outcome thromboembolism. Results The study population included 5386 patients with incident nonvalvular atrial fibrillation and type 2 diabetes mellitus. Compared with patients with HbA1c ≤48 mmol/mol, we observed a higher risk of thromboembolism among patients with HbA1c=49-58 mmol/mol (hazard ratio, 1.49; 95% CI, 1.09-2.05) and HbA1c >58 mmol/mol (hazard ratio, 1.59; 95% CI, 1.13-2.22) after adjusting for confounding factors. When stratified on diabetes mellitus duration, similar results were found among patients with diabetes mellitus duration of <10 years. Contrastingly, in patients with diabetes mellitus duration of ≥10 years, higher HbA1c levels were not associated with a higher risk of thromboembolism. Conclusions In patients with incident atrial fibrillation and type 2 diabetes mellitus, increasing levels of HbA1c were associated with a higher risk of thromboembolism. However, no association was found among patients with diabetes mellitus duration ≥10 years. [ABSTRACT FROM AUTHOR]

The use of warfarin to prevent thromboembolism in patients with infective endocarditis (IE) remains controversial due to potentially increased bleeding risks. Population-based retrospective cohort study. Patients aged 18 or older and diagnosed with IE in Hong Kong between January 1st, 1997 and August 31st, 2020 were included. Patients with use of any anticoagulant 30 days before IE diagnosis were excluded. Patients initiated on warfarin within 14 days of IE diagnosis and patients without warfarin use were matched for baseline characteristics using 1:1 propensity score matching. Warfarin use within 14 days of IE diagnosis. Patients were followed up to 90 days for the outcomes of ischemic stroke, all-cause mortality, intracranial hemorrhage, and gastrointestinal bleeding. Cox regression was used to determine hazard ratios (HRs) [95 % confidence intervals (CIs)] between treatment groups. Fine-Gray competing risk regression with all-cause mortality as the competing event was performed as a sensitivity analysis. In addition to 90-day analyses, landmark analyses were performed at 30 days of follow-up. The matched cohort consisted of 675 warfarin users (57.0 % male, age 59 ± 16 years) and 675 warfarin non-users (53.5 % male, age 61 ± 19 years). Warfarin users had a 50 % decreased 90-day risk in all-cause mortality (HR:0.50 [0.39–0.65]), without significantly different 90-day risks of ischemic stroke (HR:1.04 [0.70–1.53]), intracranial hemorrhage (HR:1.25 [0.77–2.04]), and gastrointestinal bleeding (HR:1.04 [0.60–1.78]). Thirty-day landmark analysis showed similar results. Competing risk regression showed significantly higher 30-day cumulative incidence of intracranial hemorrhage in warfarin users (sub-HR:3.34 [1.34–8.31]), but not at 90-day (sub-HR:1.63 [0.95–2.81]). Results from Fine-Gray regression were otherwise congruent with those from Cox regression. Warfarin initiated within 14 days of IE diagnosis was associated with significantly decreased risks of mortality but higher risks of intracranial hemorrhage, with similar risks of ischemic stroke and gastrointestinal bleeding, compared with non-use of warfarin with 14 days of IE diagnosis. Question : Is warfarin, initiated within 14 days of a diagnosis of infective endocarditis (IE), efficacious and safe? Findings : In this propensity score-matched, population-based, prospective cohort study from Hong Kong, warfarin use within 14 days of IE diagnosis was associated with a 50 % decrease in the risk of all-cause mortality, albeit with higher risk of intracranial hemorrhage, and without significant differences in the risk of ischaemic stroke and gastrointestinal bleeding. Meaning : In patients with IE, warfarin use within 14 days of diagnosis may have mortality benefits, despite increased risks of intracranial hemorrhage. • Limited data exists regarding the safety and efficacy of using warfarin as an anticoagulant in treatment of IE. • Initiating warfarin shortly after IE diagnosis was associated with reduced 90-day mortality risk by 50% compared to no use. • The decrease in mortality remained consistent after excluding patients who received cardiac surgery or heparin. • Warfarin use was not associated with 90-day ischemic stroke risk compared to non-use. • Initiating warfarin did not increase 90-day risks of intracranial hemorrhage or gastrointestinal bleeding. [ABSTRACT FROM AUTHOR]

Low-grade endotoxemia is associated with systemic inflammation, enhanced oxidative stress and cardiovascular events in different clinical settings, but its possible role as "second hit" in patients with primary antiphospholipid syndrome (PAPS) has never been investigated. To evaluate the relationship between plasma lipopolysaccharide (LPS) levels, oxidative stress markers and risk of thrombosis in the prospective multicenter ATHERO-APS study. Baseline LPS, soluble NADPH-oxidase 2-derived peptide (sNOX-dp), H 2 O 2 production, hydrogen peroxide breakdown activity (HBA), and nitric oxide (NO) bioavailability were compared in 97 PAPS, 16 non-thrombotic aPL carriers and 21 controls (CTRL) matched for age and sex. Correlations among laboratory variables were explored by Rho Spearman's correlation (rS). Cox-regression analysis was performed to assess the association between LPS and risk for a composite outcome of cardiovascular death, venous and arterial thromboembolism. In the whole cohort (median age 51 years (IQR 43–60), 72 % female), PAPS demonstrated higher levels of LPS, sNOX-dp and H 2 O 2 and lower levels of NO and HBA compared to non-thrombotic aPL carriers and CTRL. LPS levels were inversely correlated with HBA (rS: −0.295, p = 0.001) and NO (rS: −0.322, p < 0.001) and directly correlated with sNOX-dp (rS:0.469, p < 0.001) and H 2 0 2 (rS:0.282, p < 0.001). PAPS showed higher levels of LPS, sNOX-dp and H 2 O 2 and lower levels of NO and HBA compared to aPL carriers and CTRL. After a 4.7 years follow-up of, 11 composite outcomes were reported in PAPS (2.5 per 100 patient-years) while none was observed in aPL carriers. On Cox-regression analysis, patients with LPS above the median (>23.1 pg/ml) had a 5-fold increased risk of composite outcome compared to those with LPS below the median, after adjustment for sex, age, diabetes, and global antiphospholipid syndrome score. Low-grade endotoxemia is associated with an increased oxidative stress and a higher risk of thrombosis in PAPS. Its prognostic value in carriers needs to be investigated in larger cohorts. • Antiphospholipid antibodies trigger thrombotic events according to a "second hit" hypothesis. • The role of LPS as a possible "second hit" has never been investigated in patients with PAPS. • Plasma LPS concentration is associated with increased oxidative stress and with a higher risk of recurrent thrombosis in PAPS. • This finding opens new insights into the possible prognostic role of LPS in PAPS. [ABSTRACT FROM AUTHOR]

No abstract available Copyright © 2010 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Examines the risk of thromboembolism in atrial fibrillation in Denmark. Use of prophylaxis in patients with atrial fibrillation; Risk factors of acute arterial occlusion; Correlation between acute arterial occlusion and atherosclerosis.

Abstract: Background: Vascular disease (including myocardial infarction and peripheral artery disease) has been proposed as a less well-validated risk factor for stroke in patients with atrial fibrillation. We investigated whether vascular disease is an independent risk factor of stroke/thromboembolism in atrial fibrillation and whether adding vascular disease improves Congestive heart failure, Hypertension, Age 75 years, Diabetes, previous Stroke (CHADS2) risk stratification. Methods: By using nationwide Danish registers, we identified all patients discharged with atrial fibrillation and not treated with vitamin K antagonist or heparin between 1997 and 2008. The rate of stroke/thromboembolism in patients with atrial fibrillation with and without vascular disease was determined, and the risk associated with vascular disease was estimated in Cox regression analyses. The value of adding vascular disease to the CHADS2 score was evaluated by Net Reclassification Improvement and Integrated Discrimination Improvement. Results: We included 87,202 patients with non-valvular atrial fibrillation; of these, 15,212 (17.4%) had vascular disease, 11,750 (77.2%) had myocardial infarction, 2503 (16.5%) had peripheral artery disease, and 959 (6.3%) had both. In patients with a CHADS2 score=0, the rate of stroke/thromboembolism at 1-year follow-up was 2.31 (1.63-3.26) and 1.52 (1.34-1.73) per 100 person-years in patients with and without vascular disease, respectively. Vascular disease increased the risk of stroke/thromboembolism in both univariate (hazard ratio [HR] 1.26; confidence interval [CI], 1.18-1.35) and multivariate (HR, 1.12; CI, 1.05-1.21) analyses. The risk of stroke/thromboembolism associated with peripheral artery disease alone (HR, 1.93; CI, 1.70-2.19) was greater than the risk with myocardial infarction alone (HR, 1.12; CI, 1.04-1.21), and vascular disease significantly improved the predictive ability of the CHADS2 score (Net Reclassification Improvement 0.032, P<.001). Conclusions: Vascular disease is an independent predictor of stroke/thromboembolism in atrial fibrillation and improves the predictive ability of the CHADS2 score. [Copyright &y& Elsevier]

The article presents a study tracing the effectiveness of direct thrombin inhibitors (DTIs) in comparison with low-molecular-weight heparin (LMWH) or vitamin K antagonists (VKAs) for prevention of venous thromboembolism (VTE) after total hip replacement (THR). According to meta-analysis by C. A. Salazar and colleagues DTIs have similar effect as that of LMWHs and VKAs in prevention of VTE but higher mortality rate. A chart presenting comparison forDTIs and LMWH, is also presented.

Background Oral anticoagulant therapy is central to the prevention thromboembolic events in atrial fibrillation (AF) patients. The SAMe-TT 2 R 2 score is a simple clinical-derived score designed to aid decision-making on whether or not a patient is likely to achieve good anticoagulation control on vitamin K Antagonists (VKA, e.g. warfarin). Good anticoagulation control is associated with optimal VKA efficacy and safety. Methods The SAMe-TT 2 R 2 score was studied in a large cohort of warfarin-treated non-valvular AF patients from the SPORTIF trials, and related to time in therapeutic range (TTR) as measure of anticoagulation control, and thromboembolism-related outcomes. Results Among the 3665 patients originally assigned to the warfarin arm, a SAMe-TT 2 R 2 score > 2 was found in 19.5%. In these patients, a linear relationship was reported between SAMe-TT 2 R 2 score and TTR (p < 0.001). SAMe-TT 2 R 2 > 2 was inversely associated with a higher proportion with TTR > 65% (p = 0.014) or TTR > 70% (p = 0.011). Patients with SAMe-TT 2 R 2 score > 2 had a significantly higher event rate of the composite thromboembolism-related outcome, vs. SAMe-TT 2 R 2 0–2 (10.2% vs. 7.9%, p = 0.045). On survival analysis, SAMe-TT 2 R 2 > 2 was associated with a higher risk for the composite outcome (Log-Rank: 5.471, p = 0.019). On Cox regression, a SAMe-TT 2 R 2 score > 2 was independently associated with the composite outcome (p = 0.020). Conclusions In this large trial cohort of AF patients, the SAMe-TT 2 R 2 score was able to identify patients more likely to obtain suboptimal anticoagulation control on VKA, with an increase in major thromboembolism-related adverse events consequent upon such poor anticoagulation control. [ABSTRACT FROM AUTHOR]

• The clinical complexity of atrial fibrillation (AF) patients is increasing with population aging and multimorbidity is associated with higher risk of adverse outcomes. • In the past 3 years, four new AF international guidelines or focused updates have been published, highlighting the centrality of this evolving field. • Thromboembolic and bleeding risks evaluation at baseline and reassessment during follow-up was evenly recommended. • Oral anticoagulants prescription was consistently recommended. • Latest guidelines emphasize the importance of a holistic and integrated approach to patient care. Clinical practice in atrial fibrillation (AF) patient management is constantly evolving. In the past 3 years, various new AF guidelines or focused updates have been published, given this rapidly evolving field. In 2019, the American College of Cardiology/American Heart Association published a focused update of the 2014 guidelines. In 2020, both the European Society of Cardiology and the Canadian Cardiovascular Society released their new guidelines. Finally, the most recent guidelines were those published in 2021 by the Asian Pacific Heart Rhythm Society, which updates their 2017 version and the 2021 National Institute for Health and Care Excellence (NICE) guidelines. In the present narrative review, we compare these guidelines, emphasizing similarities and differences in the following mainstay elements of patient care: thromboembolic risk assessment, oral anticoagulants (OACs) prescription, bleeding risk evaluation, and integrated patient management. A formal evaluation of baseline thromboembolic and bleeding risks and their reassessment during follow-up is evenly recommended, although some differences in using risk stratification scores. OACs prescription is highly encouraged where appropriate, and prescription algorithms are broadly similar. The importance of an integrated and multidisciplinary approach to patient care is emerging, aiming to address several different aspects of a multifaceted disease. [ABSTRACT FROM AUTHOR]

Bleeding is the most dreaded complication of anticoagulant therapy for acute venous thromboembolism (VTE). Limited data exist about patient characteristics, time course and outcomes of major bleeding, according to the bleeding site. We used the data from the Registro Informatizado Enfermedad TromboEmbólica (RIETE) registry (03/2001–07/2018) and identified patients who suffered from major bleeding during anticoagulation. We assessed patient characteristics, time course, and 30-day outcomes including mortality, re-bleeding, and VTE recurrences, according to bleeding site. Among 78,136 patients with VTE receiving anticoagulation, 2244 (2.9%) suffered from major bleeding (gastrointestinal in 800, intracranial in 417, hematoma in 410, genitourinary in 222, retroperitoneal in 145; other sites in 250). There were variations in baseline characteristics, including older age (P < 0.001) and predominance of women (70.2% [95% confidence interval [CI]]: 65.6–74.6% versus 50.5%, 95% CI: 48.2–52.9, P < 0.001) in patients with hematoma, compared with other patients. Overall, 82.7% of hematomas and 81.4% of retroperitoneal bleeds occurred in the first 90 days after the diagnosis of the VTE event, compared with only 50.6% of intracranial bleeds. Across the bleeding subgroups, 30-day all-cause mortality rates were highest in patients who suffered from intracranial bleeding (41.0%; 99% confidence interval [CI]: 34.8–47.4%), and lowest in patients who suffered from hematoma (17.8%; 99% CI: 13.2–23.2%). Patients who suffered from a major bleeding event in the first 30 days after VTE had significantly higher odds at 90-day follow-up to develop mortality (including from bleeding), recurrent VTE, and recurrent major bleeding (all Ps < 0.001). Variations were observed in the results according to the bleeding site. Major bleeding is a serious complication in VTE patients. Patient characteristics, time course and outcomes varied substantially according to the bleeding site. Additional studies are needed to tease out the impact of patient risk factors, treatment regimens, and a potential distinct effect from the site of bleeding. https://clinicaltrials.gov/ct2/show/NCT02832245 (RIETE registry). • In a large of study of patients with major bleeding in the course of anticoagulation for venous thromboembolism (VTE), there were distinctions in the time course of bleeding events according to the bleeding site. Intracranial bleeds accrued gradually over the course of a year, whereas most of the hematomas and retroperitoneal bleeds occurred within the first 30 days. • Patient characteristics had distinctions based on the site of bleeding, including older age and a greater proportion of women among patients who had hematoma. • Among patients with major bleeding, 30-day mortality rates were highest in those who had intracranial hemorrhage. [ABSTRACT FROM AUTHOR]

Atrial fibrillation (AF) is the commonest sustained cardiac arrhythmia, which is associated with a substantial risk of stroke and thromboembolism. A prothrombotic or hypercoagulable state has been observed in these patients, although previous studies have mainly focused on various clotting factors, endothelial damage or dysfunction markers and platelet activation. However, fibrinolytic function has been less frequently studied, despite the fibrinolytic system playing an important role in preventing intravascular thrombosis. Indeed, increasing evidence suggests that an imbalance between the fibrinolytic function is of great importance in cardiovascular disease. This review will begin by providing a brief approach to fibrinolytic function and examine previous studies about fibrinolytic activity and atrial fibrillation. [Copyright &y& Elsevier]

Patients with cardiac implantable electronic device (CIED) developing atrial high-rate episodes (AHRE) have a significant risk of thromboembolic events (TEs), but risk factors have been scarcely investigated. To analyze risk factors for TEs in a contemporary cohort of patients with CIED. Consecutive non-AF patients without anticoagulation at baseline were followed up after the CIED implantation. The role of newly-developed AHRE and other risk factors for TEs were analyzed using a time-dependent Cox regression model and Kaplan-Meier analysis with log-rank tests. A total of 594 CIED patients were followed up for a mean of 4.2 years: 175 developed AHRE (29.5%; incident rate [IR] 8.80% per patient-year). Of those, 33 experienced TEs (5.5%; IR 1.38% per patient-year). Incidence of TEs was low in patients with a CHA 2 DS 2 -VASc score < 2 (male)/<3 (female) (AHRE vs. no-AHRE, 0.60% vs. 0.00% per patient-year, p = 0.469) and high in those with score ≥ 2 (male)/≥3 (female) (AHRE vs. no-AHRE, 2.12% vs. 1.36% per patient-year, p = 0.209), regardless of the AHRE presence. AHRE was not significantly associated with TEs (hazard ratio [HR], 1.46 [0.64–3.33]). There was no temporal relationship between AHRE and TEs. Baseline CHA 2 DS 2 -VASc score was independently associated with TEs (HR, 1.41 [1.13–1.75]) on multivariate analysis, but not AHRE. Thromboembolic risk in patients with CIED is mainly driven by comorbidity burden, i.e., CHA 2 DS 2 -VASc score, rather than AHRE per se. Decision-making on stroke prevention needs to focus on comorbidity burden and not merely on the presence or absence of AHRE in CIED patients. • Thromboembolic risk in CIED is driven by comorbidities, rather than AHRE per se. • Higher CHA 2 DS 2 -VASc score increases thromboembolism in non-AF patients. • Decision-making on stroke prevention should focus on comorbidity burden. • AHRE has no temporal relationship with thromboembolism. [ABSTRACT FROM AUTHOR]

Abstract Prescription of anticoagulants (ACs) in patients with cancer and atrial fibrillation (AF) is challenging and the impact on survival is not defined. In this study data prospectively collected in Oncology Units were retrospectively evaluated. Among 4664 patients admitted for malignancy, 394 patients (8.4%) had documented AF (mean age of 74 ± 9) and AC was prescribed to 155 patients (40%). Neither the type of cancer, the stage of the disease (metastatic or not) nor the ongoing treatments were significantly associated with prescription of AC, which was independently associated with BMI (OR 1.10; CI 95% 1.03–1.17; p =.003), valvular heart disease (OR 3.76; CI95% 1.59–8.87; p =.002), and previous venous thromboembolism (OR 6.67; 95%CI 2.67–16.70; p <.001). During a median follow-up of 212 days, survival from all-cause death was 37%, 28% and 18% at 6 months, 1 and 2 years, respectively. Only variables related to neoplastic disease or to patient clinical complexity were independently associated with mortality. A CHA 2 DS 2 VASc ≥ 4 was significantly associated with mortality (HR 1.33; 95%CI 1.06–1.67; p =.013). Treatment with ACs was not significantly related to mortality, neither in the whole cohort of patients, nor in patients with metastatic malignancies. In conclusion the prescription of ACs in patients with AF and active cancer was suboptimal, with one fourth of the patients not treated with ACs and one third using LMWH at prophylactic, non-therapeutic doses. Only few variables (BMI, valvular heart disease and previous venous thromboembolism) predicted prescription of ACs. Prescription of ACs was not associated with all-cause mortality, even in the subgroup with metastasis. Highlights • Prescription of anticoagulants in cancer patients with atrial fibrillation (AF) is challenging. • The impact on survival of AF and associated treatments in advanced cancer is not defined. • In a real-world analysis performed in an Oncology Unit we found that prescription of anticoagulants was suboptimal. • Anticoagulants were not significantly associated with mortality even in patients with metastatic malignancies. • Only variables related to neoplastic disease or to patient clinical complexity were independently associated with mortality. [ABSTRACT FROM AUTHOR]

Background Atrial fibrillation is a common cause of stroke, and diabetes increases stroke risk. Stroke risk may vary depending on the type of diabetes. We investigated whether type 1 and type 2 diabetes are associated with different risks of thromboembolism among patients with atrial fibrillation. Methods We used data from Danish nationwide registries to identify patients with a prior diagnosis of diabetes and an incident nonvalvular atrial fibrillation diagnosis in the period of January 1, 2005 to December 31, 2015. Cox regression analysis was used to estimate hazard ratios (HR) for the outcome thromboembolism. Results The study population included 10,058 patients with a prior diagnosis of diabetes and an incident diagnosis of atrial fibrillation. At three-year follow-up, type 2 diabetes was not associated with a higher risk of thromboembolism compared to type 1 diabetes, with an adjusted HR of 1.15 (95% CI: 0.91–1.44). In an age-stratified analysis, patients aged below 65 years of age had an adjusted HR of 1.97 (95% CI: 1.07–3.61), whereas patients aged 65–74 years or ≥75 years had adjusted HRs of 0.99 (95% CI: 0.67–1.46) and 1.10 (95% CI: 0.80–1.51), respectively. Conclusion We found no overall credible association between the type of diabetes and risk of thromboembolism in this cohort of non-anticoagulated patients with incident atrial fibrillation. Nonetheless, the subset of patients aged below 65 years of age displayed a higher risk of thromboembolism among patients with type 2 diabetes as compared to patients with type 1 diabetes. [ABSTRACT FROM AUTHOR]

Background: Atrial fibrillation (AF) patients on a vitamin K antagonist (VKA) with time in therapeutic range (TTR) ≥70% are not recommended to switch to a direct oral anticoagulant according to guidelines.Objectives: This study sought to assess future TTR and risk of stroke/thromboembolism and major bleeding among AF patients on VKA with TTR ≥70%.Methods: The authors used Danish nationwide registries to identify AF patients on VKA from 1997 to 2011 with available international normalized ratio values. Patients were included 6 months after VKA initiation, divided according to TTR, and followed for 12 months after inclusion. Cox proportional hazard models estimated hazard ratios (HRs). TTR was examined both as a baseline variable and as a time-dependent covariate in the Cox models.Results: Of the 4,772 included AF patients still on VKA 6 months after initiation, 1,691 (35.4%) had a TTR ≥70%, and 3,081 (65.6%) had a TTR <70%. Among patients with prior TTR ≥70% still on treatment 12 months after inclusion, only 513 (55.7%) still had a TTR ≥70%. Compared with prior TTR ≥70%, prior TTR <70% was not associated with a higher risk of stroke/thromboembolism (HR: 1.14; 95% confidence interval [CI]: 0.77 to 1.70) or major bleeding (HR: 1.12; 95% CI: 0.84 to 1.49). When the authors estimated TTR time-dependently during follow-up, TTR <70% was associated with an increased risk of stroke/thromboembolism (HR: 1.91; 95% CI: 1.30 to 2.82) and major bleeding (HR: 1.34; 95% CI: 1.02 to 1.76).Conclusions: Among AF patients on VKA, almost one-half of patients with prior TTR ≥70% had TTR <70% during the following year. Prior TTR ≥70% per se had limited long-term prognostic value. [ABSTRACT FROM AUTHOR]

Aims We compared thromboembolic (TE) and bleeding risks in patients with atrial fibrillation (AF) according to the new ‘Evaluated Heartvalves, Rheumatic or Artificial’ (EHRA) valve classification. Methods Patients were divided into 3 categories: (i) EHRA type 1 corresponds to the previous ‘valvular’ AF patients, with either rheumatic mitral valve stenosis or mechanical prosthetic heart valves; (ii) EHRA type 2 includes AF patients with other valvular heart disease (VHD) and valve bioprosthesis or repair; and (iii) ‘non-VHD controls’ i.e. all AF patients with neither VHD nor post-surgical valve disease. Results Among 8962 AF patients seen between 2000 and 2010, 357 (4%) were EHRA type 1, 1754 (20%) were EHRA type 2 and 6851 (76%) non-VHD controls. EHRA type 2 patients were older and had a higher CHA 2 DS 2 -VASc and HAS-BLED scores than either type 1 and non-VHD patients. After a mean follow-up of 1264 ± 1160 days, the occurrence of TE events was higher in EHRA type 2 than non-VHD patients (HR (95%CI): 1.30 1.09–1.54), p  = 0.003; also, p  = 0.31 for type 1 vs 2, p  = 0.68 for type 1 vs non-VHD controls). The rate of major BARC bleeding events for AF patients was higher in either EHRA type 1 (HR (95%CI): 3.16(2.11–4.72), p  < 0.0001) or type 2 (HR (95%CI): 2.19(1.69–2.84), p  < 0.0001) compared to non-VHD controls. Conclusion The EHRA valve classification of AF patients with VHD appears useful in categorizing these patients, in terms of TE and bleeding risks. This classification can be used in clinical practice for appropriate choices of oral anticoagulation therapy and follow-up. [ABSTRACT FROM AUTHOR]

Background: There is uncertainty whether a focus on modifiable bleeding risk factors offers better prediction of major bleeding than other existing bleeding risk scores.Methods: This study compared a score based on numbers of the modifiable bleeding risk factors recommended in the 2016 European guidelines ("European risk score") versus other published bleeding risk scores that have been derived and validated in atrial fibrillation subjects (HEMORR2HAGES, HAS-BLED, ATRIA, and ORBIT) in a large hospital-based cohort of Chinese inpatients with atrial fibrillation.Results: The European score had modest predictive ability for major bleeding (c-index 0.63, 95% confidence interval 0.56-0.69) and intracranial hemorrhage (0.72, 0.65-0.79) but nonsignificantly (and poorly) predicted extracranial bleeding (0.55, 0.54-0.56; P = .361). The HAS-BLED score was superior to predict bleeding events compared with the European score, with the differences between c-indexes of 0.10-0.12 (Delong test, all P < .05), net reclassification improvement values of 13.0%-34.5% (all P < .05), and integrated discrimination improvement values of 0.7%-1.4% (all P < .05). The European score had similar predictive value to other bleeding risk schemes (HEMORR2HAGES, ATRIA, and ORBIT) for major bleeding and intracranial hemorrhage (all P > .05). Decision curve analysis clearly shows that HAS-BLED had better net benefit of predicting major bleeding compared with the European score.Conclusions: Relying on bleeding risk assessment using modifiable bleeding risk factors alone is an inferior strategy for predicting atrial fibrillation patients for major bleeding. Our observations reaffirm the Asian guideline recommendations with HAS-BLED for bleeding risk assessment in patients with atrial fibrillation. [ABSTRACT FROM AUTHOR]

Sex and gender differences have been reported in atrial fibrillation (AF), especially in relation to differences in thromboembolic and bleeding risks. More recently, pharmacological treatments have changed following the introduction of non-vitamin K antagonist oral anticoagulants (NOACs) progressively replacing vitamin K antagonists (VKAs). The aims of this systematic review are to summarize the available evidence on NOACs and the relationship to major adverse outcomes according to sex. Moreover, we performed a meta-analysis of data from the phase III clinical trials investigating the sex effect on stroke/systemic embolic events (SEE) and major bleeding. Our literature review found small differences in NOACs efficacy and safety between male and female patients, even if so far available literature is limited to post-hoc ancillary analyses from randomized trials and one cohort study. Meta-analysis from NOAC trials found a differential effect of NOACs, with male patients being more protected from stroke/SEE and female patients more protected from major bleeding events. Further data are needed to fully elucidate sex differences in AF patients treated with NOACs. [ABSTRACT FROM AUTHOR]

A bidirectional relationship exists between atrial fibrillation (AF) and chronic renal disease. Patients with AF have a higher incidence of renal dysfunction, and the latter predisposes to incident AF. The coexistence of both conditions results in a higher risk for thromboembolic-related adverse events but a paradoxical increased hemorrhagic risk. Oral anticoagulants (both vitamin K antagonists [VKAs] and non-VKA oral anticoagulants [NOACs]) have been demonstrated to be effective in mild to moderate renal dysfunction. Patients with severe renal impairment were excluded from the non-VKA oral anticoagulant trials, so limited data are available. In end-stage renal failure, the net clinical benefit of VKAs in dialysis-dependent patients remains uncertain, although some evidence suggests that such patients may do well with high-quality anticoagulation control. Risk stratification and careful follow-up of such patients are necessary to ensure a net clinical benefit from thromboprophylaxis. [ABSTRACT FROM AUTHOR]

Background Female sex is associated with thromboembolism related to atrial fibrillation (AF). Left atrial (LA) diameter independently predicted incident cardiovascular (CV) major events in the general population. In AF patients, LA enlargement is associated to AF occurrence and recurrence. No data have previously been reported on the relationship between LA enlargement, sex and CV death in AF patients. Methods and results All patients enrolled in the AFFIRM Trial with available data about LA dimension were included in this post-hoc analysis. Of the 2615 eligible for the present analysis, LA enlargement was recorded in 67.0%, more commonly in women than in men (p = 0.032). Patients with LA enlargement had higher body mass index (BMI), and were more frequently hypertensive, diabetic, and diagnosed with a structural heart disease, prior coronary artery disease (CAD) and heart failure (HF). BMI, left ventricular mass, female sex and mitral valve insufficiency (p < 0.001) were associated with LA enlargement. AF female patients with LA enlargement had a higher risk for CV death (p = 0.011). LA diameter showed a significant association with CV death (p < 0.001). Cox regression analysis demonstrated that LA diameter was an independent predictor of CV death in female AF patients (p = 0.003). Conclusions LA diameter enlargement is associated with female sex, and carries a higher risk for CV death, particularly in females. LA diameter was an independent predictor of CV death in female AF patients. [ABSTRACT FROM AUTHOR]

Background Oral anticoagulation is highly effective in preventing stroke and mortality in nonvalvular atrial fibrillation patients. However, the efficacy and safety of vitamin K antagonists (the main oral anticoagulation drug used) strongly depends upon the quantity of anticoagulation control, as reflected by the average percentage of the time in therapeutic range of international normalized ratio 2.0-3.0. An easy, simple prediction of which atrial fibrillation patients are likely to do well on vitamin K antagonists (with good average time in therapeutic range) could guide decision-making between using vitamin K antagonists (eg, warfarin) and non-vitamin K antagonist oral anticoagulants. Methods and Results In a consecutive cohort of nonvalvular atrial fibrillation patients attending our anticoagulation clinic, we tested the hypothesis that the new Sex, Race, Medical history, Tobacco use, Race (SAMe-TT 2 R 2 ) score was a predictor for good average time in therapeutic range, and second, this would translate into adverse events in a “real world” cohort of patients with nonvalvular atrial fibrillation. The incidence of bleeding, adverse cardiovascular events (including stroke/thromboembolism), and mortality during the follow-up was higher with increasing SAMe-TT 2 R 2 score. The SAMe-TT 2 R 2 score was predictive for the composite of all adverse events (hazard ratio 1.32 [95% Confidence Interval 1.17-1.50]; P <.001), adverse cardiovascular events (1.52 [1.28-1.83]; P <.001), and all-cause mortality (1.41 [1.16-1.67]; P = .001). A trend was also observed for major bleeding events (1.23 [0.99-1.53]; P = .059). Conclusion In a “real world” cohort of consecutive patients with nonvalvular atrial fibrillation, a high SAMe-TT 2 R 2 score (reflecting poor anticoagulation control with poor time in therapeutic range) was associated with more bleeding, adverse cardiovascular events, and mortality during follow-up. [ABSTRACT FROM AUTHOR]