Thromboembolic Complications Of Atrial Fibrillation Research Articles

Thromboembolic complications in atrial fibrillation

Thromboembolic complications in atrial fibrillation

#3896 SAFETY OUTCOMES OF ORAL ANTICOAGULANT THERAPY IN PATIENTS WITH ATRIAL FIBRILLATION AND CHRONIC KIDNEY DISEASE

Abstract Background and Aims The comorbid conditions of atrial fibrillation (AF) and chronic kidney disease (CKD) leads to an increased risk of thromboembolic complications, but on the other hand is a risk factor for various bleeding. Oral anticoagulant therapy is the standard for the prevention of thromboembolic complications in AF. But with the deterioration of kidney function, the risk of hemorrhagic complications increases dramatically. This problem makes it difficult to choose an effective and safe oral anticoagulant therapy. Clinical data on the use of new oral anticoagulants (NOACs) in patients with AF and advanced CKD are limited, which determines the relevance of conducting studies in comparison with vitamin K antagonists. The aim of study was evaluation of safety parameters for the using of rivaroxaban in patients with stage 4 CKD with AF. Method The study included 109 patients over the age of 18 with a diagnosis of stage 4 CKD (eGFR – 15–29 ml/min/1.72 m2) and non-valvular AF. They were randomized in a 2:1 ratio to either rivaroxaban 15 mg (n = 73) or warfarin (n = 36). The mean follow-up period was 18 months. In the warfarin group, time in therapeutic range (TTR) >70% was achieved in 34 (94%) patients. Exclusion criteria were a history of bleeding that required hospitalization; decrease in hemoglobin level below 80 g/l, platelet count below 100 × 109/l; indications for taking antiplatelet therapy; chronic use of drugs that increase the risk of bleeding. The analysis of the observed hemorrhagic events was carried out using the BARC and ISTH scales. Classification of anemia was carried out according to the recommendations of the World Health Organization. Results Patients taking warfarin were significantly more likely to develop minor bleeding according to the BARC scales and ISTH and all clinically significant bleeding on the ISTH scale. In patients with AF and CKD receiving warfarin therapy, minor bleeding (MB) according to the BARC scale was observed in 72.2% (n = 26), minor clinically significant bleeding (MCSB) in 8.33% (n = 3), major bleeding in 8.33% (n = 3) of cases; and in the group of patients treated with rivaroxaban, MB was observed in 42.4% (n = 31, p<0.01), MCSB in 2.74% (n = 2, p = 0.32), major bleeding in 2.74% (n = 2, p = 0.32) of cases. When assessing bleeding on the ISTH scale during therapy with VKA, MB – 61.1% (n = 22), MCSB – 19.4% (n = 7), major bleeding – 8.33% (n = 3); against the background of NOACs therapy, MB – 36.9% (n = 27, p = 0.01), MCSB in 8.2% (n = 6, p = 0.06), major bleeding in 2.74% (n = 2, p = 0.32). All clinically significant hemorrhagic events according to the BARC scale in the warfarin group occurred more than 16.6% (n = 6) compared with the rivaroxaban group 5.4% (n = 4, p = 0.06); when analyzed according to the ISTH scale, the number of patients receiving VKA anticoagulant therapy 27.7% (n = 10) significantly prevailed over patients on the background of NOACs 10.9% (n = 8, p = 0.03). Analysis of hemoglobin level did not reveal significant dynamics and significant differences between the groups: the median hemoglobin level at inclusion was 129 g/l in the rivaroxaban group and 123 g/l in the warfarin group (p = 0.3), after 18 months - 130 g/l and 121 g/l, respectively (p = 0.7). Conclusion Data suggesting a favorable safety profile for NOACs (rivaroxaban) compared with VKAs (warfarin) in patients with AF and advanced CKD was obtained in this study. Taking rivaroxaban was accompanied by a significantly lower number of hemorrhagic events, which may indicate a safe effect of the drug. No significant changes in hemoglobin levels were found in both groups. Confirmation of these data may be key in choosing an anticoagulant in patients with AF and advanced CKD.

Management of patients with atrial fibrillation and minor bleeding during therapy with direct oral anti-coagulants

The recommended tactics for prevention of thromboembolic complications of atrial fibrillation (AF) is the oral anticoagulant (OAC) treatment. The drugs of choice for preventing stroke for most patients with AF, excluding some valvular defects, are direct OACs (DOACS). Regardless of the drug class, all anticoagulants, even at appropriate doses, increase the risk of bleeding. However, the development of minor bleedings is not an absolute indication for DOAC withdrawal. This review presents a tactics for management of patients with minor bleeding associated with the DOAC treatment.

Problems of adherence to treatment with oral anticoagulants in elderly patients with atrial fibrillation in the Kyrgyz Republic

Objectives assessment of adherence to treatment in elderly patients with nonvalvular atrial fibrillation who were prescribed anticoagulant therapy with vitamin K antagonist, warfarin, and a new oral anticoagulant rivaroxaban.
 Material and methods. During the study, 322 patients with atrial fibrillation of nonvalvular etiology were observed. Depending on the type of anticoagulant taken, the patients were divided into 2 groups: the first group included 253 (78.6%) people who took warfarin, the second group 69 (21.4%) people, who were prescribed a new oral anticoagulant rivaroxaban.
 Results. By the end of the one-year follow-up from the start of anticoagulant treatment, only 8.7% of patients in the first group followed the doctor's prescription; the second group had 59.4% of adherent patients. The vast majority of patients refused warfarin therapy due to the inability to control INR. In the case of the appointment of rivaroxaban, the reason for the refusal to take was the high cost of the drugs.
 Conclusion. Effective prevention of thromboembolic complications in atrial fibrillation requires the development of appropriate measures to improve adherence to treatment.

Primary Non-adherence to Treatment with New Oral Anticoagulants: The Results of a Prospective Observational Study «ANTEY»

Aim: To assess the main characteristics of patients with non-valvular Atrial Fibrillation (AF) who are initially non-adherent to New Oral Anticoagulants (NOAC), and to identify factors associated with this version of non-adherence. Materials and Methods: The ANTEY study included 201 patients with non-valvular AF, who had indications and without contraindications for NOAC treatment. The patients had previously been advised to take oral anticoagulants but they did not comply with all medical recommendations. The observation period was 1 year, during which 2 in-person visits were performed: an inclusion visit (V0) and a visit (V1), as well as 1 telephone contact/follow up (FU); the interval between contacts was 6 months. All patients were recommended to take the NOAC by decision of the physician. During the V0, V1 and FU visits, the “National Society for Evidence-Based Pharmacotherapy (NSEPh) Adherence Scale” questionnaire was used to assess overall adherence and associated factors. 15 (7.5%) patients had not started NOAC therapy by the end of the study (primary non-adherent patients). Their characteristics are analysed in this work. Results: The main reasons for primary non-adherence to NOAC were high cost (33.3%), fears of adverse effects (AE) (33.3%), doubts about the need for treatment (13.3%) and the complex therapy regimen (13.3%). In the group of primary non-adherent patients in comparison with the rest of the patients there were significantly more patients with 1 point according to CHADS2VASc (20% and 2.2%, respectively, p = 0.029) and patients with 3 points according to HAS-BLED (33.3% and 9.1%, respectively, p = 0.006); they took antiplatelet drugs more often 73.3% versus 21.5%, respectively (p = 0.001). Full employment at work (OR = 5.2; CI95% [1.5; 18.1], p = 0.009), history of quitting smoking (OR = 5.1; CI95% [1.5; 17.0], p = 0,008), the presence of any pharmacotherapy AE (OR = 4.0; CI95% [1.01; 16.0], p = 0.048) increased the chance of primary non-adherence to NOAC by 4-5 times. Conclusion: The most vulnerable in relation to initiation of NOAC therapy for the prevention of thromboembolic complications in AF are those patients who continue to work or have any pharmacotherapy AE. The leading factors preventing the initiation of NOAC administration are their high cost, fear of the development of AE from the therapy, and patients’ doubts about the need for treatment with these drugs. The clinical trial registration number is NCT 03790917.

Current practice and future prospects in left atrial appendage occlusion.

The thromboembolic complications of Atrial fibrillation (AF) remain a major problem in contemporary clinical practice. Despite advances and developments in anticoagulation strategies, therapy is complicated by the high risk of bleeding complications and need for meticulous medication compliance. Over the past few decades, the left atrial appendage has emerged as a promising therapeutic target to prevent thromboembolic events while mitigating bleeding complications and compliance issues. Emerging data indicates that it is a safe, effective and feasible alternative to systemic anticoagulation in patients with non-valvular AF. A number of devices have been developed for endocardial or epicardial based isolation of the left atrial appendage. Increasing experience has improved overall procedural safety and ease while simultaneously reducing device related complication rates. Furthermore, increasing recognition of the non-mechanical advantages of this procedure has led to further interest in its utility for further indications beyond the prevention of thromboembolic complications. In this review, we present a comprehensive overview of the evolution of left atrial appendage occlusion, commercially available devices and the role of this modality in the current management of AF. We also provide a brief outline of the landmark trials supporting this approach as well as the ongoing research and future prospects of left atrial appendage occlusion.

Topical Issues in Diagnosis of Coagulopathies and Prevention of Thromboembolic Complications of Atrial Fibrillation in Patients with Liver Cirrhosis

Nowadays the comorbid pathology of liver cirrhosis and atrial fibrillation has been widely discussed and reported in the literature in the light of recent findings from the study of the effectiveness and safety of anticoagulants in this category of patients. The review is devoted to summarizing the existing data on the comorbid course of these diseases from the point of view of the impact of bleeding and thrombosis on the quality of life and mortality of patients and the possibility of using new methods of diagnosis and prevention of these complications.
 The purpose of the review is to focus the attention of physicians and researches on the relevance and prevalence of comorbid course of liver cirrhosis and atrial fibrillation, their complications, and discuss the benefits and possibilities of applying global methods of hemostasis assessment and anticoagulants in clinical practice.
 This article examines the main pathophysiological aspects of «rebalanced hemostasis» theory in liver coagulopathies, its effect on the onset of bleeding and thrombotic events, and considering the clinical benefit of the use of anticoagulants. The disadvantages of traditional coagulation assessment tests compared to the benefits of thromboelastometry (ROTEM) and thromboelastography (TEG), general fulfilling principles and evaluation of their indicators are discussed. Existing research findings on the safety and efficacy of warfarin and direct oral anticoagulants in patients with liver cirrhosis and atrial fibrillation compared with no treatment are highlighted.

Research of spontaneous and stimulated functional activity of platelets in patients with different types of atrial fibrillation.

Platelet function testing is widely used to diagnose disorders of the cellular link of hemostasis. The study of platelet aggregation activity is relevant for the prevention of thromboembolic complications in atrial fibrillation and monitoring the effectiveness and safety of therapy. In this study, a comparative analysis of spontaneous and stimulated platelet aggregation in groups of patients with two types of atrial fibrillation was performed - paroxysmal and persistent. The effect of β-adrenoblocker therapy on platelet aggregation activity in patients with atrial fibrillation was also studied. Platelet aggregation activity was studied using the method of G. Born in the modification of Z.A. Gabbasov on a two-channel laser analyzer "Biola". Collagen at a concentration of 2 mg / ml and adrenaline in a concentration range of 2.5-10 μg / ml were used as aggregation-promoting agents. It has been established that spontaneous aggregation potential and collagen-induced platelet aggregation depend on the type of atrial fibrillation, as well as on the presence or absence of β-blockers in therapy. The response of platelets to stimulation with adrenaline depends, first of all, on the type of atrial fibrillation and the concentration of adrenaline in the reaction medium. The most significant changes were noted in the group of patients with a paroxysmal form atrial fibrillation, taking β-blockers in therapy.

P1426 Non-cardiac sourses of thromboembolic complications in atrial fibrillation

Abstract Background Thromboischemic stroke is a significant medical problem. The most dangerous arrhythmia that causes the thromboembolism is atrial fibrillation. The source of thrombus mostly located in left atrium appendage or apex of left ventricle. But there’re a lot of cases of thromboischemic stroke in patients with atrial fibrillation without any intra-heart thrombus. Purpose To study the possibility of thromboembolic complications in patients with permanent form of atrial fibrillation without intra-heart thrombus. Materials and methods We included 48 patients with permanent form of atrial fibrillation. Mediana age - 68 ± 4,6 y.o. 32 (66,7%) were men and 16 (33,3%) women. All patients were performed 24-hours ECG monitoring to verify the atrial fibrillation. 34 (70,8%) were regularly took warfarin or NOACs to prevent the thromboembolic complications. We used CHADS-2 scale to make the prognosis of 1-year thromboembolic complications. 0 points - 0 (0%) patients, 1 point - 1 (2,1%), 2 points - 2 (4,2%), 3 points - 8 (16,6%), 4 points - 7 (14,5%), 5 points - 18 (37,5%), 6 points - 12 (25,1%). All patients were made transesophageal echocardiography. Only 3 (6,2%) of them had intra-heart thrombus. Intra-arterial blood flow we measured with Doppler-ultrasound. Most of patients – 39 (81,3%) had atherosclerotic plaques of internal carotid artery on one or both sides. In 22 (45,8%) patients were the signs of non-stability of plaques (heterogenic structure, rough surface). We valued the arterial wall kinetic parameters with sphygmography: speed, acceleration, power, work. We analyzed these parameters in different cardiocycles. Results We observed the following patterns: 1. If longer was the pause between cardiocycles in atrial fibrillation then more increase of biomechanical and kinetic parameters was observed. 2. The secondary hemodynamic arterial hypertension at the moments after long pause between cardiocycles. The longest duration of it was observed in bradysystolic atrial fibrillation (up to 38% of time). 3. In patients with hemodynamically important stenosis (about 70%) of internal carotid artery the speed after the long pause in atrial fibrillation is rising up to 4-4,5 meters per second. In comparison with sinus rhythm it is about 2,3 meters per second. Such rising of speed can cause the plaque integrity damage of parietal thrombus fragmentation. 4. Increased arterial wall deformation. The increased biomechanical parameters cause the appearance of additional waves, stand waves that may cause non-stability of plaques with further thromboembolism. 5. During the 1-year observation thromboembolic comlications appeared in 11 (22,9%) patients. Conclusion The source of thromboembolic complications can be non-cardiac in patients with multi-focus atherosclerosis and non-stable plaques.

Safety of Using Direct Oral Anticoagulants in Patients with Atrial Fibrillation and Chronic Kidney Disease

The purpose of this review is to examine the possibilities and prospects for the use of direct oral anticoagulants for the prevention of thromboembolic complications in patients with atrial fibrillation and chronic kidney disease. Chronic kidney disease is an independent risk factor for cardiovascular complications. Atrial fibrillation is associated with a higher risk of developing chronic kidney disease and more rapid progression of existing renal pathology. The presence of chronic kidney disease in atrial fibrillation on the one hand leads to an increased risk of thromboembolism, and on the other to an increased risk of bleeding when using anticoagulants. The standard for the prevention of thromboembolic complications in atrial fibrillation, including those with concomitant renal pathology, was considered warfarin for many years. However, modern studies have shown that the use of warfarin may enhance vascular calcification in patients with chronic kidney disease, which in turn may lead to an increased risk of ischemic strokes.Analyzing clinical recommendations, randomized studies, meta-analyzes and a systematic review on the use of anticoagulants in patients with atrial fibrillation and renal pathology, revealed the advantage of using direct oral anticoagulants over warfarin at stage 1-3 of chronic kidney disease. Data on the use of direct oral anticoagulants with a more pronounced renal dysfunction and in patients on dialysis is limited due to the lack of a sufficient number of large randomized studies. Due to the presence of renal clearance in all oral anticoagulants, their pharmacokinetics changes to some extent with a decrease in the glomerular filtration rate, which requires dose adjustment of drugs depending on creatinine clearance. Therefore, the use of anticoagulants for the prevention of thromboembolic complications during atrial fibrillation requires special attention in patients with chronic kidney disease.

Quality and determinants of anticoagulation therapy by AVK in elderly subjects: study of a continuous series of 155 patients hospitalized in geriatric medicine

AVK could be prescribed in elderly patients over 75 years for the prevention of thromboembolic complications of atrial fibrillation (AF). The objective of this study was to study the quality of the anticoagulation balance by AVK and its determinants. Inclusion of all patients ≥ 75 years of age treated with AVK for an AF hospitalized in the acute geriatric department of the University hospital of Dijon. The balance of the AVK treatment was determined by the input INR and the calculation of the TTR. The last four INRs prior to admission were retrospectively collected for its calculation. Each patient had a standardized geriatric evaluation (EGS): lifestyle, MMSE, nutritional status (albumin), polypathology (Charlson), level of dependence (ADL-IADL). Bleeding complication were collected. 155 patients aged over 75 years (87±5.6 years, 88 women and 67 men) were included. The mean TTR was 55.4±31.2%. Only 46% of patients had a correct TTR (≥ 75%). The balance was significantly worse in women than in men (49.3±29.5 vs 60.1±31.8%; p=0.0326), and in case of haematological pathology (41.7±27.1 vs 57.2± 9.8; p=0.047) but better with high BMI (r=0.416, p=0.001). No EGS parameters were associated with the quality of anticoagulation. The control of AVK therapy is insufficient in geriatric elderly subjects. No modifiable explicative geriatric factor has been identified. If AVK remains a therapeutic option, direct oral anticoaulants should be considered as the first choice.

Interventions for Preventing Thromboembolic Events in Patients With Atrial Fibrillation: A Systematic Review.

The comparative safety and effectiveness of treatments to prevent thromboembolic complications in atrial fibrillation (AF) remain uncertain. To compare the effectiveness of medical and procedural therapies in preventing thromboembolic events and bleeding complications in adults with nonvalvular AF. English-language studies in several databases from 1 January 2000 to 14 February 2018. Two reviewers independently screened citations to identify comparative studies of treatments to prevent stroke in adults with nonvalvular AF who reported thromboembolic or bleeding complications. Two reviewers independently abstracted data, assessed study quality and applicability, and rated strength of evidence. Data from 220 articles were included. Dabigatran and apixaban were superior and rivaroxaban and edoxaban were similar to warfarin in preventing stroke or systemic embolism. Apixaban and edoxaban were superior and rivaroxaban and dabigatran were similar to warfarin in reducing the risk for major bleeding. Treatment effects with dabigatran were similar in patients with renal dysfunction (interaction P > 0.05), and patients younger than 75 years had lower bleeding rates with dabigatran (interaction P < 0.001). The benefit of treatment with apixaban was consistent in many subgroups, including those with renal impairment, diabetes, and prior stroke (interaction P > 0.05 for all). The greatest bleeding risk reduction was observed in patients with a glomerular filtration rate less than 50 mL/min/1.73 m2 (P= 0.003). Similar treatment effects were observed for rivaroxaban and edoxaban in patients with prior stroke, diabetes, or heart failure (interaction P > 0.05 for all). Heterogeneous study populations, interventions, and outcomes. The available direct-acting oral anticoagulants (DOACs) are at least as effective and safe as warfarin for patients with nonvalvular AF. The DOACs had similar benefits across several patient subgroups and seemed safe and efficacious for a wide range of patients with nonvalvular AF. Patient-Centered Outcomes Research Institute. (PROSPERO: CRD42017069999).

EFFICACY OF ISCHEMIC STROKE PREVENTION IN PATIENTS WITH IMPLANTED OCCLUDER OF THE LEFT ATRIUM. FIVE YEAR FOLLOW-UP

Aim. In the study we set an aim to evaluate the rate of thromboembolic complications in atrial fibrillation (AF) patients with implanted occluding device of the left atrium appendage (LAA).Material and methods. Beginning at 2012, in the study center, 102 LAA occluders were implanted, of those 44 Watchman device (Boston Scientific), 55 Amplatzer Cardiac Plug (AGA Medical), and 3 Amulet (Abbott). Total follow-up 304,8 patientyears, mean follow-up duration 2,98±1,72 y.Results. During the period, 1 (0,98%) case of acute stroke was registered and 1 case of transient cerebral ischemia. Control transesophageal assessment was done in 100 patients, in 4 (4%) cases there was transient thrombosis of atrial area of the device with no significant outcomes.Conclusion. Implantation of the LAA occluder is an alternative for anticoagulation in AF patients with high thromboembolic and not possible drug prevention.

Антикоагулянтная терапия у больных с фибрилляцией предсердий в особых ситуациях: сахарный диабет, хроническая болезнь почек

Conducting anticoagulant therapy for atrial fibrillation, combined with diabetes mellitus and/or chronic kidney disease, can create certain difficulties for practicing doctors due to a simultaneous increase in the risk of thromboembolic and hemorrhagic complications. The presence of diabetes mellitus and renal dysfunction can influence the results of antithrombotic therapy in patients with atrial fibrillation. The review provides information on the differences in efficacy and safety of individual oral anticoagulants in the prevention of thromboembolic complications of atrial fibrillation in patients with diabetes mellitus, impaired renal function.

Основные принципы лечения и профилактики инсультов как тромбоэмболических осложнений фибрилляции предсердий. Анализ рекомендаций Европейского общества кардиологов по лечению фибрилляции предсердий 2016 года

Основные принципы лечения и профилактики инсультов как тромбоэмболических осложнений фибрилляции предсердий. Анализ рекомендаций Европейского общества кардиологов по лечению фибрилляции предсердий 2016 года

Novel (Oral) Anticoagulant Challenges in Surgery.

SummaryNon-vitamin K oral anticoagulants (NOACs) are a relatively recent therapeutic modality for the prevention of systemic thromboembolic complications of atrial fibrillation and the prevention and management of venous thromboembolic disease. Approved indications for this class of anticoagulants are likely to further expand as the results of ongoing and new clinical trials are published and clinical experience grows. Despite their convenience compared with traditional methods of anticoagulation, there remain a few potential pitfalls associated with their use in the perioperative setting. In particular, there is limited experience and evidence base regarding anticoagulant management in the perioperative setting, especially given the different NOACs available, which in turn are different from the classical anticoagulants. This narrative review synthesizes the recent advances in development of specific NOAC reversal agents and the understanding of the complexities of laboratory measurement of NOAC anticoagulant effects, and aims to provide practicing clinicians with basic evidence-based tools for perioperative management of patients taking NOACs.

Arterial hypertension as a risk factor of intra-atrial thrombosis in patients with atrial fibrillation of non-valvular etiology

38 patients were examined (26 men and 12 women) aged 35 to 75 years with documented AF. Paroxysmal AF was diagnosed in 10 patients (26.32%). The persistent and permanent forms of arrhythmia were revealed in 14 cases (36.84%). Stage II-III hypertensive disease (HD) was diagnosed in 27 patients (71.1%). The transthoracic and transesophageal echocardiography was performed with the use of ultrasonic devices such as Aloka-SSD-4000 ProSound (Japan) and PhilipsIE 33 (USA). The analysis of results of echocardiography (both transthoracic and transesophageal) made it possible to detect intra-atrial clots in 54,8% of the patients with AF of non-valvular etiology. Atrial cavity thrombosis was registered in 15 of the 22 cases (68,2%) among the patients with hypertension as a direct cause of AF or another concomitant pathology. Lower blood flow velocity from the left atrial appendage was registered in hypertensive patients compared to those without hypertension - 29.0 (4.2) and 35.4 respectively (8.1) mm/s (p = 0.038; Student's t-test). The reduction of the peak bloodflow velocity in the left atrial appendage was proportional to the increase of hypertension (R = -0,861; p <0,001; R - Spearman's coefficient). The frequency of intra-atrial thrombosis did not depend on the form of atrialfibrillation and duration of the arrhythmic anamnesis. Hypertension is an independent predictor of thromboembolic complications in atrial fibrillation of non-valvular etiology.

Apixaban 5 mg Twice Daily and Clinical Outcomes in Patients With Atrial Fibrillation and Advanced Age, Low Body Weight, or High Creatinine: A Secondary Analysis of a Randomized Clinical Trial.

In the Apixaban for Reduction of Stroke and Other Thromboembolic Complications in Atrial Fibrillation (ARISTOTLE) trial, the standard dose of apixaban was 5 mg twice daily; patients with at least 2 dose-reduction criteria-80 years or older, weight 60 kg or less, and creatinine level 1.5 mg/dL or higher-received a reduced dose of apixaban of 2.5 mg twice daily. Little is known about patients with 1 dose-reduction criterion who received the 5 mg twice daily dose of apixaban. To determine the frequency of 1 dose-reduction criterion and whether the effects of the 5 mg twice daily dose of apixaban on stroke or systemic embolism and bleeding varied among patients with 1 or no dose-reduction criteria. Among 18 201 patients in the ARISTOTLE trial, 17 322 were included in this analysis. Annualized event rates of stroke or systemic embolism and major bleeding and hazard ratios (HRs) and 95% CIs were evaluated. Interactions between the effects of apixaban vs warfarin and the presence of 1 or no dose-reduction criteria were assessed. The first patient was enrolled in the ARISTOTLE trial on December 19, 2006, and follow-up was completed on January 30, 2011. Data were analyzed from January 2015 to May 30, 2016. Analysis of major bleeding included events during study drug treatment. Analysis of stroke or systemic embolism was based on intention to treat. Of the patients with 1 or no dose-reduction criteria assigned to receive the 5 mg twice daily dose of apixaban or warfarin, 3966 had 1 dose-reduction criterion; these patients had higher rates of stroke or systemic embolism (HR, 1.47; 95% CI, 1.20-1.81) and major bleeding (HR, 1.89; 95% CI, 1.62-2.20) compared with those with no dose-reduction criteria (n = 13 356). The benefit of the 5 mg twice daily dose of apixaban (n = 8665) compared with warfarin (n = 8657) on stroke or systemic embolism in patients with 1 dose-reduction criterion (HR, 0.94; 95% CI, 0.66-1.32) and no dose-reduction criterion (HR, 0.77; 95% CI, 0.62-0.97) were similar (P for interaction = .36). Similarly, the benefit of 5 mg twice daily dose of apixaban compared with warfarin on major bleeding in patients with 1 dose-reduction criterion (HR, 0.68; 95% CI, 0.53-0.87) and no dose-reduction criterion (HR, 0.72; 95% CI, 0.60-0.86) were similar (P for interaction = .71). Similar patterns were seen for each dose-reduction criterion and across the spectrum of age, body weight, creatinine level, and creatinine clearance. Patients with atrial fibrillation and isolated advanced age, low body weight, or renal dysfunction have a higher risk of stroke or systemic embolism and major bleeding but show consistent benefits with the 5 mg twice daily dose of apixaban vs warfarin compared with patients without these characteristics. The 5 mg twice daily dose of apixaban is safe, efficacious, and appropriate for patients with only 1 dose-reduction criterion. clinicaltrials.gov Identifier: NCT00412984.

Role of Platelets in Thromboembolism in Patients with Atrial Fibrillation.

Thromboembolic complications of atrial fibrillation (AF) are a major cause of morbidity and mortality but the mechanism of its process remain poorly understood. There are many as yet unanswered questions surrounding the increased thrombotic tendency in AF. One of the crucial questions is what determines the fact that a thrombus remains in the left atrium in situ in some patients, while in others it breaks off and leads to embolic complications. Recent studies indicated an important role of platelets in the left atrial's thrombus formation and suggest that the embolic potential of left atrial thromboses depends on the involvement of platelets in the process of fibrin stabilization rather than aggregation. New methods for investigating platelets function, such as the analysis of transcription activity of RNA coming from platelets contained in thrombi formed in AF, creates an opportunity for studying populations of platelets that are directly involved in homeostatic clot formation. In this paper we present current opinions on the participation of platelets in the pathogenesis of thromboembolism in patients with AF.

Percutaneous Left Atrial Appendage Ligation for Stroke Prevention in Atrial Fibrillation.

Prevention of thromboembolic complications in atrial fibrillation remains a tremendous clinical challenge. Knowledge that the left atrial appendage (LAA) is the most common anatomical origin of cardioembolic strokes1 has been the main motivation to develop clinical and procedural strategies to exclude the LAA from the circulation, either surgically or percutaneously. This review discusses the rationale behind these strategies, their relative merits, and future prospects for LAA exclusion strategies.