BACKGROUND & AIMS: :Dabigatran is a newly available oral direct thrombin inhibitor approved for anticoagulation therapy to prevent strokes in patients with nonvalvular atrial fibrillation. Unlike warfarin, dabigatran's observed therapeutic window and minimal drug-to-drug interaction suggest that invasive laboratory testing and dose adjustment is not necessary. In circumstances of excessive anticoagulation, such as overdoses, decreased kidney function, or instances of significant bleeding, reversing dabigatran's effects may be necessary. Unlike warfarin, no rapid-acting antidote to reverse the effects of dabigatran is known. However, hemodialysis has been suggested as a method of removing dabigatran and thereby reducing its anticoagulant effect. We describe a case in which hemodialysis was used in an attempt to remove dabigatran in a patient with excessive anticoagulation from dabigatran and severe intracranial hemorrhage. Serial dabigatran levels suggested that hemodialysis removed the drug. However, given the large volume of distribution of dabigatran in the terminal phase of elimination, a rebound in drug level was noted. We suggest that a longer duration of therapy or more continuous modality of hemodialysis may be needed in conjunction with the initial hemodialysis treatment of dabigatran coagulopathy.

背景与目标： 达比加群是一种新获得的口服直接凝血酶抑制剂，被批准用于抗凝治疗，以预防非瓣膜性房颤患者的中风。与华法林不同，达比加群观察到的治疗窗口和最小的药物与药物相互作用表明，没有必要进行侵入性实验室测试和剂量调整。在过度抗凝的情况下，例如过量，肾功能下降或大量出血，逆转达比加群的作用可能是必要的。与华法林不同，没有快速作用的解毒剂可以逆转达比加群的作用。然而，血液透析已被建议作为去除达比加群的方法，从而降低其抗凝作用。我们描述了一个案例，其中使用血液透析试图从达比加群中抗凝过度并严重颅内出血的患者中去除达比加群。连续的达比加群水平表明血液透析去除了药物。然而，鉴于达比加群在消除的最后阶段的大量分布，注意到药物水平反弹。我们建议，与达比加群凝血病的初始血液透析治疗相结合，可能需要更长的治疗时间或更连续的血液透析方式。

BACKGROUND & AIMS: INTRODUCTION:The objective of the present study was to evaluate, from an economic perspective, dabigatran etexilate in comparison to existing pharmaceutical therapeutic options available for the protection of moderate-to-high risk patients with non-valvular atrial fibrillation from cardioembolic risk. METHODS:An existing Markov model was adapted to the Greek setting to reflect the natural course of the disease and the management of patients with different therapies. The model predicts health and economic outcomes and the implications for the social security system during the course of a patient's lifetime. The data for the population of the model were derived from the international literature and local economic databases. RESULTS:The incremental cost per quality-adjusted life year (QALY) of dabigatran 150 mg twice daily relative to the other therapies varied from €5547 to €11,762 and that of dabigatran 110 mg twice daily from €7398 to €16,437. The incremental cost per QALY of dabigatran 150 mg relative to aspirin, the least costly option, was €11,762 and relative to warfarin and acenocoumarol, the local standards of care, it was €11,400 and €11,224 respectively, well below the local thresholds of acceptance. CONCLUSION:Dabigatran etexilate may represent a cost-effective option for the prevention of thromboembolic events in AF patients at moderate-to-high risk of stroke or systemic embolism.

背景与目标：

BACKGROUND & AIMS: :Essentials Factor Xa inhibitors cause more abnormal menstrual bleeding (AUB) than vitamin-K antagonists (VKA). We analyzed data of AUB in women, evaluating dabigatran versus VKA. We observed a 41% lower risk of AUB in women on dabigatran compared to those on VKA. Our findings of lower AUB risk on dabigatran should be corroborated in future studies. SUMMARY:Introduction Although direct oral anticoagulants (DOACs) are associated with a better safety profile than warfarin in patients with acute venous thromboembolism (VTE), direct factor Xa inhibitors involve a higher risk of abnormal uterine bleeding (AUB). We aimed to determine the risk of AUB during anticoagulation with dabigatran compared with warfarin. Methods Post-hoc analysis of the pooled RE-COVER studies and the RE-MEDY trial. Incidences of AUB, based on a defined preferred terms search for adverse events, in female patients aged 18-50 years treated with dabigatran, were compared with those in women treated with warfarin. Results Of the 2964 women included in the above-mentioned trials, 1280 women were in the relevant age category (18-50 years) and included in the current analysis. A total of 643 patients were randomized to treatment with dabigatran and 637 to treatment with warfarin. The overall rate of AUB was 8.1%, 5.9% for the women treated with dabigatran and 9.6% in those treated with warfarin, for an odds ratio for dabigatran-treated patients of 0.59 (95% confidence interval [CI], 0.39-0.90; P = 0.015). In the dabigatran-treated patients, three (0.5%) suffered major bleeding (MB) vs. five (0.8%) in the warfarin-treated patients (HR, 0.65; 95% CI, 0.15-2.72). MB or non-major relevant bleeding occurred in 30 (4.7%) patients randomized to receive dabigatran and 57 (8.9%) randomized to receive warfarin (HR, 0.53; 95% CI, 0.34-0.83). None of the bleeding events was fatal. Conclusion Dabigatran treatment was associated with a significantly (41%) lower risk of AUB than warfarin. Future studies in daily practice are needed to corroborate these findings.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:Treatment with non-vitamin K antagonist oral anticoagulants (NOACs) such as dabigatran (a direct thrombin inhibitor) or rivaroxaban (a direct inhibitor of factor [F] Xa) attenuates atherosclerotic plaque progression in hypercholesterolemic mice. PURPOSE:To evaluate the effect of NOACs application on the expression of coagulation proteins in loco within stenotic aortic valves and in valve interstitial cells (VICs) from patients with severe aortic stenosis (AS). METHODS:Primary cultures of VICs obtained from 90 patients undergoing aortic valve replacement were stimulated with TNF-α (50 ng/mL) and pre-treated with rivaroxaban (1 and 10 ng/mL) or dabigatran (25 and 250 ng/mL). The expression of coagulation proteins was analyzed by immunofluorescence. Cytokine levels were measured by ELISA. RESULTS:FX, FXa, FVII, thrombin and PAR1/2 were present in loco within human aortic stenotic valves. Cultured VICs exhibited constant expression of FX, TF, PAR1/2. Exposure of VICs to TNF-α caused the upregulated expression of TF, PAR1/2 and induced expression of thrombin, FVII and FXa. FX was expressed by 80% of VICs, regardless of stimulation. Cultured VICs were able to synthesize metalloproteinases 1-3, IL-6, IL-32, IL-34, osteopontin and osteocalcin, the levels of which increased under TNF-α stimulation. NOACs added to culture inhibited coagulation factor and PAR1/2 expression. Moreover, NOACs down-regulated VIC-derived proteins responsible for valve calcification and extracellular matrix remodeling. CONCLUSIONS:NOACs at therapeutic concentrations may inhibit the effects of FXa and thrombin at in vitro level. It might be speculated that long-term treatment with rivaroxaban or dabigatran could attenuate the progression of AS in humans.

背景与目标：

BACKGROUND & AIMS: OBJECTIVES:The optimal timing of anticoagulation after ischemic stroke in atrial fibrillation (AF) patients is unknown. Our aim was to demonstrate the feasibility and safety of initiating dabigatran therapy within 14 days of transient ischemic attack (TIA) or minor stroke in AF patients. PATIENTS AND METHODS:A prospective, multi-center registry (NCT02415855) in patients with AF treated with dabigatran within 14 days of acute ischemic stroke/TIA (National Institutes of Health Stroke Scale (NIHSS) ≤ 3) onset. Baseline and follow-up computed tomography (CT) scans were assessed for hemorrhagic transformation (HT) and graded by using European Cooperative Acute Stroke Study criteria. RESULTS:One hundred and one patients, with a mean age of 72.4 ± 11.5 years, were enrolled. Median infarct volume was 0 ml. Median time from index event onset to dabigatran initiation was 2 days, and median baseline NIHSS was 1. Pre-treatment HT was present in seven patients. No patients developed symptomatic HT. On the day 7 CT scan, HT was present in six patients (one progressing from baseline hemorrhagic infarction type 1). Infarct volume was a predictor of incident HT (odds ratio = 1.063 [1.020-1.107], p < 0.003). All six (100%) patients with new/progressive HT were functionally independent (modified Rankin Scale (mRS) = 0-2) at 30 days, which was similar to those without HT (90%, p = 0.422). Recurrent ischemic events occurred within 30 days in four patients, two of which were associated with severe disability and death (mRS 5 and 6, respectively). CONCLUSION:Early dabigatran treatment did not precipitate symptomatic HT after minor stroke. Asymptomatic HT was associated with larger baseline infarct volumes. Early recurrent ischemic events may be clinically more important.

背景与目标：

BACKGROUND & AIMS: BACKGROUND: Physiological age-related changes in the haemostatic and coagulation systems result in differing anticoagulant assay responses to standard anticoagulants. Therefore, we investigated the response of anticoagulant assays to dabigatran etexilate (DE) in children compared with adults. OBJECTIVE: This article assesses the relationship between plasma dabigatran concentration and coagulation assay results across age groups in children and adults. PATIENTS AND METHODS: Data from three clinical trials in which children received DE following standard of care for venous thromboembolism were compared with data from adult clinical trials. The effects of dabigatran concentration on diluted thrombin time (dTT), ecarin clotting time (ECT) and activated partial thromboplastin time (aPTT) were analysed graphically and with modelling. RESULTS: The concentration-dTT relationships were consistent in children across all ages and adults in the graphical analysis. For ECT and aPTT, relationships based on ratios over baseline were similar across all ages; absolute clotting times showed that the same exposure resulted in longer clotting times in some of the children aged < 1 year versus adults. Modelling showed concentration-clotting time relationships for all three assays were largely comparable between adults and children, except in those aged < 2 months, in whom there was a slight upward shift in ECT and aPTT relative to adults. CONCLUSION: Results suggest that developmental haemostatic changes will have little impact on response to DE. However, further paediatric clinical trials assessing the relationship between coagulation assay responses and clinical outcomes will be needed to confirm this finding.

背景与目标：

BACKGROUND & AIMS: PURPOSE:Left atrial catheter ablation for patients with atrial fibrillation (AF) requires periprocedural anticoagulation to minimize thromboembolic complications. High rates of major bleeding complications using dabigatran etexilate for periprocedural anticoagulation have been reported, raising concerns regarding its safety during left atrial catheter ablation. We sought to evaluate the safety and efficacy of a dabigatran use strategy versus warfarin, at a single high-volume AF ablation center. METHODS:We performed a retrospective analysis on consecutive patients undergoing left atrial ablation at Vanderbilt Medical Center from January 2011 through August 2012 with a minimum follow-up of 3 months. Patient cohorts were divided into two groups, those utilizing dabigatran etexilate pre- and post-ablation and those undergoing ablation on dose-adjusted warfarin, with or without low-molecular-weight heparin bridging. Dabigatran was held 24-30 h pre-procedure and restarted 4-6 h after hemostasis was achieved. We evaluated all thromboembolic and bleeding complications at 3 months post-ablation. RESULTS:A total of 254 patients underwent left atrial catheter ablation for atrial fibrillation or left atrial flutter. Periprocedural anticoagulation utilized dabigatran in 122 patients and warfarin in 135 patients. Three late thromboembolic complications occurred in the dabigatran group (2.5 %), compared with one (0.7 %) in the warfarin group (p = 0.28). The dabigatran group had similar minor bleeding (2.5 vs. 7.4 %, p = 0.07), major bleeding (1.6 vs. 0.7 %, p = 0.51), and composite of bleeding and thromboembolic complications (6.6 vs. 8.9 %, p = 0.49) when compared to warfarin. There were no acute thromboembolic complications in either group (<24 h post-ablation). CONCLUSIONS:In patients undergoing left atrial catheter ablation for AF or left atrial flutter, use of periprocedural dabigatran etexilate provides a safe and effective anticoagulation strategy compared to warfarin. A prospective randomized study is warranted.

背景与目标：

BACKGROUND & AIMS: OBJECTIVES:The aim of this observational study was to explore dabigatran concentrations in elderly and very elderly patients in a real-life population. Patients aged >75 years receiving dabigatran have a significantly higher risk of gastrointestinal bleeding compared withthose receiving warfarin. High trough concentrations have an important impact on this bleeding risk. METHODS:We measured dabigatran trough concentrations in 75 patients with atrial fibrillation, divided into age categories <75, ≥75 to 84 and ≥85 years. The most important exclusion criteria were use of interacting medication and severe renal failure. We analysed absolute trough concentrations and concentrations normalised for dose. RESULTS:Trough concentrations were considerably higher in the highest age category. Dose-normalised medians were 0.66, 0.83 and 1.20 ng/mL/mg in the <75, ≥75-84 and ≥85 age groups, respectively (p=0.004). CONCLUSION:Clinicians should be aware of higher dabigatran concentrations in elderly patients despite dose reduction.

背景与目标：

BACKGROUND & AIMS: :The National Institute for Health and Clinical Excellence (NICE) invited the manufacturer of dabigatran etexilate (Boehringer Ingelheim Ltd, UK) to submit evidence for the clinical and cost-effectiveness of this drug for the prevention of stroke and systemic embolism in patients with non-valvular atrial fibrillation (AF) as part of the NICE single technology appraisal process. The Centre for Reviews and Dissemination and the Centre for Health Economics at the University of York were commissioned to act as the evidence review group (ERG). This article presents a summary of the manufacturer's submission, the ERG report and the subsequent development of NICE guidance for the use of dabigatran within the UK National Health Service. Dabigatran was granted marketing authorisation by the European Medicines Agency for a sequential dosing regimen (DBG sequential), in which patients under 80 years are treated with dabigatran 150 mg twice daily (DBG150) and patients 80 years and over are given dabigatran 110 mg twice daily (DBG110). NICE decisions are bound by the marketing authorisation; therefore, the decision problem faced by the committee was whether the DBG sequential regimen was effective and cost-effective compared with warfarin or aspirin for patients with non-valvular AF and one or more risk factors. The RE-LY trial, a large multi-centre non-inferiority randomised clinical trial, was the primary source of clinical evidence. DBG150 was shown to be non-inferior, and subsequently superior to warfarin, for the primary outcome of all stroke/systemic embolism. DBG110 was found to be non-inferior to warfarin. Results were presented for a post hoc subgroup analysis for patients under and over 80 years of age, where DBG110 showed a statistically significant reduction of haemorrhagic stroke and intracranial haemorrhage in comparison to warfarin in patients over 80 years of age. This post hoc subgroup analysis by age was the basis for the licensed DBG sequential regimen. The economic evaluation compared the costs and outcomes of DBG110, DBG150 and DBG sequential against warfarin, aspirin, and aspirin plus clopidogrel. Across the three dosing regimens, dabigatran was associated with greater costs and better health outcomes than warfarin; however, DBG150 offered the most benefits and dominated DBG110 and DBG sequential (i.e. less costly and more effective). The cost-effectiveness of DBG150 was less favourable for patients well controlled on warfarin. In the first appraisal meeting, the committee issued a 'minded no' decision until additional analyses on the licensed DBG sequential regimen were presented by the manufacturer. These additional analyses indicated that the incremental cost-effectiveness ratio (ICER) of the DBG sequential regimen compared with warfarin ranged from £8,388 to £18,987 per quality-adjusted life year (QALY) gained depending on the level of monitoring costs assumed for warfarin. Patients on warfarin would need to be within therapeutic range 83-85 % of the time for the ICER to exceed £30,000 per additional QALY. Following consideration of the additional evidence and the responses from a large number of consultees and commentators, the committee recommended dabigatran as DBG sequential as an option for the prevention of stroke and systemic embolism in people with non-valvular AF with one or more risk factors for ischaemic stroke.

背景与目标： : 国家健康和临床卓越研究所 (NICE) 邀请了达比加群酯的制造商 (勃林格殷格翰有限公司，作为NICE单一技术评估过程的一部分，该药物用于预防非瓣膜性房颤 (AF) 患者的中风和全身性栓塞的临床和成本效益的证据。约克大学的审查和传播中心和卫生经济学中心被委托担任证据审查小组 (ERG)。本文介绍了制造商提交的内容，ERG报告以及随后在英国国家卫生局内使用达比加群的NICE指南的开发摘要。达比加群获得了欧洲药品管理局的连续给药方案 (DBG sequential) 的上市许可，其中80岁以下的患者每天两次接受达比加群150 mg治疗 (DBG150)，80岁及以上的患者每天两次接受达比加群110 mg治疗 (DBG110)。NICE的决定受营销授权的约束; 因此，委员会面临的决策问题是，对于非瓣膜性房颤和一种或多种危险因素的患者，与华法林或阿司匹林相比，DBG序贯方案是否有效且具有成本效益。RE-LY试验是一项大型的多中心非劣效性随机临床试验，是临床证据的主要来源。在所有卒中/全身性栓塞的主要结局中，DBG150显示非劣于华法林，随后优于华法林。发现DBG110不劣于华法林。结果是针对80岁以下和80岁以上的患者进行的事后亚组分析，其中与80岁以上的患者相比，DBG110显示出血性中风和颅内出血的统计学上显着减少。这项按年龄进行的事后亚组分析是许可的DBG序贯方案的基础。经济评估比较了DBG110，DBG150和DBG顺序对华法林，阿司匹林和阿司匹林加氯吡格雷的成本和结果。在三种给药方案中，达比加群比华法林具有更高的成本和更好的健康结果; 然而，DBG150提供了最大的益处，并且主导了DBG110和DBG顺序 (即成本更低且更有效)。对于华法林控制良好的患者，DBG150的成本效益较差。在第一次评估会议上，委员会发布了 “不考虑” 的决定，直到制造商对许可的DBG顺序方案进行了其他分析。这些额外的分析表明，与华法林相比，DBG序贯方案的增量成本效益比 (ICER) 在每个质量调整生命年 (QALY) 获得的8,388英镑至18,987英镑之间，这取决于华法林的监测成本水平。服用华法林的患者需要在83-85% 的治疗范围内，ICER每增加QALY超过30,000英镑。在考虑了其他证据以及大量咨询人员和评论员的回应之后，委员会建议达比加群作为DBG顺序疗法，作为预防具有一种或多种缺血性卒中危险因素的非瓣膜性房颤患者中风和全身性栓塞的一种选择。

BACKGROUND & AIMS: Importance:The risk of osteoporotic fracture with dabigatran use in patients with nonvalvular atrial fibrillation (NVAF) is unknown. Objective:To investigate the risk of osteoporotic fracture with dabigatran vs warfarin in patients with NVAF. Design, Setting, and Participants:Retrospective cohort study using a population-wide database managed by the Hong Kong Hospital Authority. Patients newly diagnosed with NVAF from 2010 through 2014 and prescribed dabigatran or warfarin were matched by propensity score at a 1:2 ratio with follow-up until July 31, 2016. Exposures:Dabigatran or warfarin use during the study period. Main Outcomes and Measures:Risk of osteoporotic hip fracture and vertebral fracture was compared between dabigatran and warfarin users using Poisson regression. The corresponding incidence rate ratio (IRR) and absolute risk difference (ARD) with 95% CIs were calculated. Results:Among 51 496 patients newly diagnosed with NVAF, 8152 new users of dabigatran (n = 3268) and warfarin (n = 4884) were matched by propensity score (50% women; mean [SD] age, 74 [11] years). Osteoporotic fracture developed in 104 (1.3%) patients during follow-up (32 dabigatran users [1.0%]; 72 warfarin users [1.5%]). Results of Poisson regression analysis showed that dabigatran use was associated with a significantly lower risk of osteoporotic fracture compared with warfarin (0.7 vs 1.1 per 100 person-years; ARD per 100 person-years, -0.68 [95% CI, -0.38 to -0.86]; IRR, 0.38 [95% CI, 0.22 to 0.66]). The association with lower risk was statistically significant in patients with a history of falls, fractures, or both (dabigatran vs warfarin, 1.6 vs 3.6 per 100 person-years; ARD per 100 person-years, -3.15 [95% CI, -2.40 to -3.45]; IRR, 0.12 [95% CI, 0.04 to 0.33]), but not in those without a history (0.6 vs 0.7 per 100 person-years; ARD per 100 person-years, -0.04 [95% CI, 0.67 to -0.39]; IRR, 0.95 [95% CI, 0.45 to 1.96]) (P value for interaction, <.001). Conclusions and Relevance:Among adults with NVAF receiving anticoagulation, the use of dabigatran compared with warfarin was associated with a lower risk of osteoporotic fracture. Additional study, perhaps including randomized clinical trials, may be warranted to further understand the relationship between use of dabigatran vs warfarin and risk of fracture.

背景与目标：

BACKGROUND & AIMS: :Dabigatran was non-inferior to warfarin for prevention of recurrent venous thromboembolism (VTE), and dabigatran had a lower rate of bleeding compared with warfarin in two large-scale randomised trials, RE-COVER and RE-COVER II. In this study, we investigate the efficacy and safety of dabigatran versus warfarin according to the index event that qualified the patient for enrollment, either symptomatic pulmonary embolism (PE) with or without deep-vein thrombosis (DVT), or DVT alone. We then analyse the anticoagulant effect of dabigatran vs warfarin on patients enrolled with PE. The pooled dataset for the efficacy analysis consisted of 2553 and 2554 patients who were randomised to dabigatran and warfarin, respectively. Recurrent VTE/VTE-related death during the study period and additional 30-day follow-up occurred in 2.7 % of all patients on dabigatran and in 2.4 % on warfarin (hazard ratio [HR] 1.09 [95 % confidence interval 0.77, 1.54]). In patients with PE as their index event, recurrent VTE/VTE-related death occurred in 2.9 % vs 3.1 % of patients (HR 0.93 [0.53, 1.64]). There were significantly fewer major bleeding events in patients treated with dabigatran than with warfarin (HR 0.60 [0.36, 0.99]). The pattern was similar both in patients with PE and in those with DVT alone as the index event. These analyses of the pooled dataset from the RE-COVER and RE-COVER II trials indicate that dabigatran is as effective as warfarin in preventing recurrent VTE, regardless of whether patients present with symptomatic PE (with or without DVT) or with symptomatic DVT alone. Dabigatran was also associated with a lower risk of bleeding than warfarin, regardless of the index event.

背景与目标： : 在预防复发性静脉血栓栓塞 (VTE) 方面，达比加群不逊于华法林，在两项大规模随机试验 (RE-COVER和RE-COVER II) 中，达比加群的出血率低于华法林。在这项研究中，我们根据符合患者入组条件的指数事件 (有症状的肺栓塞 (PE) 伴或不伴深静脉血栓形成 (DVT) 或单独DVT)，研究达比加群与华法林的疗效和安全性。然后，我们分析达比加群与华法林对PE患者的抗凝作用。用于疗效分析的汇总数据集由2553和2554名患者组成，他们分别被随机分配到达比加群和华法林。在研究期间和额外的30天随访期间，达比加群所有患者的2.7   % 和华法林的2.4   % 发生了VTE/VTE相关的复发性死亡 (风险比 [HR] 1.09 [95  % 置信区间0.77，1.54])。以PE为指标事件的患者中，2.9   % 比3.1   % 的患者发生VTE/VTE相关的复发性死亡 (HR 0.93 [0.53，1.64])。与华法林相比，达比加群治疗的患者的主要出血事件显著减少 (HR 0.60 [0.36，0.99])。PE患者和单纯DVT患者的模式相似。这些来自RE-COVER和RE-COVER II试验的汇总数据集的分析表明，无论患者是否出现有症状的PE (有或没有DVT) 或单独有症状的DVT，达比加群在预防复发性VTE方面与华法林一样有效。无论指数事件如何，达比加群的出血风险也低于华法林。

BACKGROUND & AIMS: BACKGROUND AND OBJECTIVE:To evaluate the cost-effectiveness of new anticoagulants and warfarin in the prevention of stroke in Chinese patients with atrial fibrillation (AF). METHODS:The Markov model was constructed to compare patients' quality-adjusted life-years (QALYs) using drug cost, the cost of the examination after taking a drug, and the incremental cost of other treatments. Both dabigatran (110 and 150 mg, twice a day) and rivaroxaban (20 mg, once a day) were compared with warfarin (3-6 mg, once a day). Willingness to pay, three times the 2018 China GDP per capita (9481.88 $), was the cost-effect threshold in our study. RESULTS:The total cost were was 5317.31$, 29673.33$, 23615.49$, and 34324.91$ for warfarin, rivaroxaban, dabigatran 110 mg bid, and dabigatran 150 mg bid, respectively. The QALYs for each of the four interventions were 11.07 years, 15.46 years, 12.4 years, and 15 years, respectively. The cost-effectiveness analysis of the three new oral anticoagulants and warfarin showed that the incremental cost-effectiveness ratio (ICER) was 5548.07$/QALY when rivaroxaban was compared with warfarin. Rivaroxaban was the most cost-effective choice and warfarin was the least. CONCLUSIONS:In Chinese patients with AF, although warfarin is cheaper, rivaroxaban has a better cost-effectiveness advantage from an economic point of view.

背景与目标：

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: Importance:Dabigatran and rivaroxaban are non-vitamin K oral anticoagulants approved for stroke prevention in patients with nonvalvular atrial fibrillation (AF). There are no randomized head-to-head comparisons of these drugs for stroke, bleeding, or mortality outcomes. Objective:To compare risks of thromboembolic stroke, intracranial hemorrhage (ICH), major extracranial bleeding including major gastrointestinal bleeding, and mortality in patients with nonvalvular AF who initiated dabigatran or rivaroxaban treatment for stroke prevention. Design, Setting, and Participants:Retrospective new-user cohort study of 118 891 patients with nonvalvular AF who were 65 years or older, enrolled in fee-for-service Medicare, and who initiated treatment with dabigatran or rivaroxaban from November 4, 2011, through June 30, 2014. Differences in baseline characteristics were adjusted using stabilized inverse probability of treatment weights based on propensity scores. The data analysis was performed from May 7, 2015, through June 30, 2016. Exposures:Dabigatran, 150 mg, twice daily; rivaroxaban, 20 mg, once daily. Main Outcomes and Measures:Adjusted hazard ratios (HRs) for the primary outcomes of thromboembolic stroke, ICH, major extracranial bleeding including major gastrointestinal bleeding, and mortality, with dabigatran as reference. Adjusted incidence rate differences (AIRDs) were also estimated. Results:A total of 52 240 dabigatran-treated and 66 651 rivaroxaban-treated patients (47% female) contributed 15 524 and 20 199 person-years of on-treatment follow-up, respectively, during which 2537 primary outcome events occurred. Rivaroxaban use was associated with a statistically nonsignificant reduction in thromboembolic stroke (HR, 0.81; 95% CI, 0.65-1.01; P = .07; AIRD = 1.8 fewer cases/1000 person-years), statistically significant increases in ICH (HR, 1.65; 95% CI, 1.20-2.26; P = .002; AIRD = 2.3 excess cases/1000 person-years) and major extracranial bleeding (HR, 1.48; 95% CI, 1.32-1.67; P < .001; AIRD = 13.0 excess cases/1000 person-years), including major gastrointestinal bleeding (HR, 1.40; 95% CI, 1.23-1.59; P < .001; AIRD = 9.4 excess cases/1000 person-years), and with a statistically nonsignificant increase in mortality (HR, 1.15; 95% CI, 1.00-1.32; P = .051; AIRD = 3.1 excess cases/1000 person-years). In patients 75 years or older or with CHADS2 score greater than 2, rivaroxaban use was associated with significantly increased mortality compared with dabigatran use. The excess rate of ICH with rivaroxaban use exceeded its reduced rate of thromboembolic stroke. Conclusions and Relevance:Treatment with rivaroxaban 20 mg once daily was associated with statistically significant increases in ICH and major extracranial bleeding, including major gastrointestinal bleeding, compared with dabigatran 150 mg twice daily.

背景与目标：

BACKGROUND & AIMS: -2

背景与目标： -2