Pattern and Impact of Off-label Underdosing of Non-Vitamin K Antagonist Oral Anticoagulants in Patients With Atrial Fibrillation Who are Indicated for Standard Dosing.


  • 影响因子:2.86
  • DOI:10.1016/j.amjcard.2020.01.044
  • 作者列表:"Cho MS","Yun JE","Park JJ","Kim YJ","Lee J","Kim H","Park DW","Nam GB
  • 发表时间:2020-05-01

:With safety concerns about increasing bleeding, off-label underdosing of non-vitamin K antagonist anticoagulants (NOACs) is common in East Asian patients with atrial fibrillation (AF). We tried to investigate the pattern of NOAC underdosing and associated clinical outcomes in patients with AF who are indicated for standard dosing. Using the Korean National Health Insurance Service database, we evaluated 16,568 patients with a new prescription of NOAC who are indicated for standard NOAC dosing and compared 4,536 patients with warfarin with respect to thromboembolic events (ischemic stroke or systemic embolization), all-cause mortality and major bleeding. Of the 16,568 patients indicated for standard NOAC dosing, 8,549 (51.9%) received off-label underdosing (50.6% rivaroxaban, 53.0% apixaban). During a median follow up of 15.0 months, as compared with warfarin, underdosing of rivaroxaban was associated with lower risks of major thromboembolic events (hazard ratio [HR]: 0.53; 95% confidence interval [CI]: 0.41 to 0.69) and all-cause mortality (HR 0.57, 95% CI: 0.41 to 0.82), and a similar risk of major bleeding (HR 1.10, 95% CI: 0.82 to 1.46). However, underdosing of apixaban was associated with similar risks of major thromboembolic events (HR: 0.90; 95% CI: 0.70 to 1.16), all-cause mortality (HR 0.94, 95 CI: 0.71 to 1.24) and major bleeding (HR 0.84, 95% CI: 0.61 to 1.17). In conclusion, in this Korean population with AF who are indicated for standard NOAC dosing, off-label underdosing is common and its clinical benefit over warfarin was inconsistent according to types of NOAC. Notably, apixaban underdosing provides no benefit in effectiveness compared with warfarin.


: 考虑到增加出血的安全性问题,非维生素k拮抗剂抗凝剂 (NOACs) 的标签外剂量不足在东亚心房颤动 (AF) 患者中很常见。我们试图研究适用于标准剂量的AF患者的NOAC剂量不足模式和相关临床结局。使用韩国国家健康保险服务数据库,我们评估了16,568例NOAC新处方患者,这些患者适用于标准NOAC剂量,并就血栓栓塞事件 (缺血性卒中或全身性栓塞) 、全因死亡率和大出血对4,536例华法林患者进行了比较.在推荐标准NOAC给药的16,568例患者中,8,549例 (51.9%) 接受了标示外剂量不足 (50.6% 利伐沙班,53.0% 阿哌沙班).在15.0个月的中位随访期间,与华法林相比,利伐沙班未用药与较低的主要血栓栓塞事件风险 (风险比 [HR]: 0.53; 95% 置信区间 [CI]: 0.41至0.69) 和全因死亡率 (HR 0.57,95% CI: 0.41至0.82),和类似的大出血风险 (HR 1.10,95% CI: 0.82 ~ 1.46)。然而,阿哌沙班剂量不足与相似的主要血栓栓塞事件 (HR: 0.90; 95% CI: 0.70 ~ 1.16) 、全因死亡率 (HR 0.94,95 CI: 0.71 ~ 1.24) 和大出血 (HR 0.84,95% CI: 0.61 ~ 1.17) 风险相关.总之,在这一符合标准NOAC剂量的韩国房颤人群中,标示外剂量不足是常见的,根据NOAC的类型,其相对于华法林的临床获益不一致.值得注意的是,与华法林相比,阿哌沙班剂量不足在有效性方面没有获益.



作者列表:["Yaghi S","Chang AD","Akiki R","Collins S","Novack T","Hemendinger M","Schomer A","Grory BM","Cutting S","Burton T","Song C","Poppas A","McTaggart R","Jayaraman M","Merkler A","Kamel H","Elkind MSV","Furie K","Atalay MK"]

METHODS:BACKGROUND AND PURPOSE:The current left atrial appendage (LAA) classification system (cLAA-CS) categorizes it into 4 morphologies: chicken wing (CW), windsock, cactus, and cauliflower, though there is limited data on either reliability or associations between different morphologies and stroke risk. We aimed to develop a simplified LAA classification system and to determine its relationship to embolic stroke subtypes. METHODS:Consecutive patients with ischemic stroke from a prospective stroke registry who previously underwent a clinically-indicated chest CT were included. Stroke subtype was determined and LAA morphology was classified using the traditional system (in which CW = low risk) and a new system (LAA-H/L, in which low risk morphology (LAA-L) was defined as an acute angle bend or fold from the proximal/middle portion of the LAA and high risk morphology (LAA-H) was defined as all others). As a proof of concept study, we determined reliability for the two classification systems, and we assessed the associations between both classification systems with stroke subtypes in our cohort and previous studies. RESULTS:We identified 329 ischemic stroke patients with a qualifying chest CT (126 cardioembolic subtype, 116 embolic stroke of undetermined source (ESUS), and 87 non-cardioembolic subtypes). Intra- and inter-rater agreements improved using the LAA-H/L (0.95 and 0.85, respectively) vs. cLAA-CS (0.50 and 0.40). The LAA-H/L led to classifying 69 LAA morphologies that met criteria for CW as LAA-H. In fully adjusted models, LAA-H was associated with cardioembolic stroke (OR 5.4, 95%CI 2.1-13.7) and ESUS (OR 2.8 95% CI 1.2-6.4). Non-CW morphology was also associated with embolic stroke subtypes, but the effect size was much less pronounced. Studies using the cLAA-CS yielded mixed results for inter- and intra-rater agreements but most showed an association between a non-CW morphology and stroke with no difference among the three non-CW subtypes. CONCLUSION:The LAA-H/L classification system is simple, has excellent intra and inter-rater agreements, and may help risk identify patients with cardioembolic stroke subtypes. Larger studies are needed to validate these findings.

作者列表:["Kim S","Namba J","Goodman AM","Nguyen T","Saunders IM"]

METHODS:PURPOSE:Low-molecular-weight heparins are currently the recommended antithrombotic therapy for treatment and prevention of malignancy-related venous thromboembolism. Currently, the evidence evaluating direct oral anticoagulants versus low-molecular-weight heparins or a vitamin K antagonist in cancer patients with hematologic malignancies is limited. We evaluated the safety and efficacy of direct oral anticoagulants for venous thromboembolism treatment or stroke prevention for non-valvular atrial fibrillation in patients with hematologic malignancies. METHODS:This was a retrospective evaluation of adult patients with hematologic malignancies who received at least one dose of the Food and Drug Administration-approved direct oral anticoagulant for venous thromboembolism treatment or stroke prevention. We determined the frequency of major bleeding events, non-major bleeding events, stroke, systemic embolism, appropriateness of initial direct oral anticoagulant doses, holding practices prior to procedures, and the rate of all-cause mortality. An analysis was also performed to compare the incidence of bleeding between patients with a history of hematopoietic stem cell transplant to non-transplant patients. RESULTS:A total of 103 patients were identified, with the majority of patients receiving rivaroxaban for venous thromboembolism treatment. Major bleeding events occurred in four patients and no fatal bleeding events occurred. Non-major bleeding occurred in 29 patients, most commonly epistaxis and bruising. Two patients experienced a systemic embolism while on direct oral anticoagulant therapy. CONCLUSION:Direct oral anticoagulants may be a safe and effective alternative for anticoagulation therapy in patients with hematologic malignancies. However, larger prospective studies comparing direct oral anticoagulants to low-molecular-weight heparins or vitamin K antagonists are warranted to compare efficacy and safety outcomes in this patient population.

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作者列表:["Harky A","Chaplin G","Chan JSK","Eriksen P","MacCarthy-Ofosu B","Theologou T","Muir AD"]

METHODS::It has been over two decades since the very first robotic cardiac surgery was performed. Over the years, there has been an increase in the demand for less invasive cardiac surgical techniques. Developments in technology and engineering have provided an opportunity for robotic surgery to be applied to a variety of cardiac procedures, including coronary revascularisation, mitral valve surgery, atrial fibrillation ablation, and others. In coronary revascularisation, it is becoming more widely used in single vessel, as well as hybrid coronary artery approaches. Currently, several international centres are specialising in a totally endoscopic coronary artery bypass surgery involving multiple vessels. Mitral valve and other intracardiac pathologies such as atrial septal defect and intracardiac tumour are also increasingly being addressed robotically. Even though some studies have shown good results with robot-assisted cardiac surgery, there are still concerns about safety, cost and clinical efficacy. There are also limitations and additional challenges with the management of cardiopulmonary bypass and myocardial protection during robotic surgery. Implementing novel strategies to manage these challenges, together with careful patient selection can go a long way to producing satisfactory results. This review examines the current evidence behind robotic surgery in various aspects of cardiac surgery.

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