BACKGROUND & AIMS: BACKGROUND:This phase 3 trial compared the efficacy and safety of rivaroxaban, an oral direct inhibitor of factor Xa, with those of enoxaparin for extended thromboprophylaxis in patients undergoing total hip arthroplasty. METHODS:In this randomized, double-blind study, we assigned 4541 patients to receive either 10 mg of oral rivaroxaban once daily, beginning after surgery, or 40 mg of enoxaparin subcutaneously once daily, beginning the evening before surgery, plus a placebo tablet or injection. The primary efficacy outcome was the composite of deep-vein thrombosis (either symptomatic or detected by bilateral venography if the patient was asymptomatic), nonfatal pulmonary embolism, or death from any cause at 36 days (range, 30 to 42). The main secondary efficacy outcome was major venous thromboembolism (proximal deep-vein thrombosis, nonfatal pulmonary embolism, or death from venous thromboembolism). The primary safety outcome was major bleeding. RESULTS:A total of 3153 patients were included in the superiority analysis (after 1388 exclusions), and 4433 were included in the safety analysis (after 108 exclusions). The primary efficacy outcome occurred in 18 of 1595 patients (1.1%) in the rivaroxaban group and in 58 of 1558 patients (3.7%) in the enoxaparin group (absolute risk reduction, 2.6%; 95% confidence interval [CI], 1.5 to 3.7; P<0.001). Major venous thromboembolism occurred in 4 of 1686 patients (0.2%) in the rivaroxaban group and in 33 of 1678 patients (2.0%) in the enoxaparin group (absolute risk reduction, 1.7%; 95% CI, 1.0 to 2.5; P<0.001). Major bleeding occurred in 6 of 2209 patients (0.3%) in the rivaroxaban group and in 2 of 2224 patients (0.1%) in the enoxaparin group (P=0.18). CONCLUSIONS:A once-daily, 10-mg oral dose of rivaroxaban was significantly more effective for extended thromboprophylaxis than a once-daily, 40-mg subcutaneous dose of enoxaparin in patients undergoing elective total hip arthroplasty. The two drugs had similar safety profiles. (ClinicalTrials.gov number, NCT00329628.)

背景与目标： 背景：这项3期试验比较了口服Xa因子直接抑制剂利伐沙班和依诺肝素对全髋关节置换术患者延长血栓预防的疗效和安全性。
方法：在这项随机，双盲研究中，我们分配4541名患者，使其在手术后开始每天一次接受10 mg口服利伐沙班治疗，或者在手术前一天晚上开始皮下每天一次接受40 mg依诺肝素的治疗，再加上安慰剂片或注射。主要疗效结果是深静脉血栓形成（有症状或如果患者无症状则可通过双侧静脉造影检查发现），非致命性肺栓塞或任何原因在36天时死亡（30至42天）。次要疗效的主要结果是主要的静脉血栓栓塞（近端深静脉血栓形成，非致命性肺栓塞或静脉血栓栓塞死亡）。主要安全结果是大出血。
结果：优势分析共纳入3153例患者（1388例除外），安全性分析共4433例（108例除外）。利伐沙班组1595例患者中有18例（1.1％）发生了主要疗效，依诺肝素组1558例中58例（3.7％）发生了（绝对风险降低2.6％； 95％置信区间[CI]为1.5至1.5）。 3.7； P <0.001）。利伐沙班组1686例患者中有4例发生严重静脉血栓栓塞（0.2％），依诺肝素组1678例患者中有33例（2.0％）发生（绝对风险降低1.7％; 95％CI为1.0至2.5; P <0.001 ）。利伐沙班组2209例患者中有6例发生大出血（0.3％），依诺肝素组2222例患者中有2例（0.1％）（P = 0.18）。
结论：对于行择期全髋关节置换术的患者，每天口服10 mg利伐沙班对延长血栓预防效果比每天一次40 mg皮下剂量依诺肝素有效。两种药物的安全性相似。 （ClinicalTrials.gov编号，NCT00329628。）

BACKGROUND & AIMS: :The localized activation of coagulation in vascular malformations can lead to a consumptive coagulopathy characterized by elevated D-dimers and a consumption of fibrinogen and platelets, eventually giving rise to a bleeding tendency. By reducing coagulation activation, anticoagulant treatment with heparin is able to limit this haemostatic dysregulation and the associated bleeding diathesis. Here, we present a case of a consumptive coagulopathy due to a large venous malformation with a sustained correction of the fibrinogen depletion and associated bleeding tendency both with subcutaneous enoxaparin and with the oral factor Xa inhibitor rivaroxaban.

背景与目标： ：血管畸形中凝血的局部激活会导致消耗性凝血病，其特征为D-二聚体升高以及纤维蛋白原和血小板的消耗，最终导致出血倾向。通过减少凝血激活，用肝素进行的抗凝治疗能够限制这种止血功能失调和相关的出血情况。在这里，我们介绍了由于皮下依诺肝素和口服因子Xa抑制剂rivaroxaban引起的大静脉畸形，纤维蛋白原消耗的持续矫正以及相关的出血倾向而导致的消耗性凝血病。

BACKGROUND & AIMS: :Bleeding is the most feared and difficult to predict adverse event of anticoagulation. We sought to investigate whether calibrated automated thrombography (CAT) parameters are associated with minor bleeding (MB) in anticoagulated patients following venous thromboembolism (VTE). Enrolled were 132 patients on rivaroxaban, 145 on vitamin K antagonists (VKA) and 31 controls who stopped anticoagulation. Prior to the next dose of the anticoagulant, we measured CAT parameters, along with rivaroxaban concentration and INR. During a median follow-up of 10 months, we recorded minor and major bleedings. On rivaroxaban, 27 (20.5%) patients with MB had longer time to start thrombin generation, lower peak thrombin generation and lower endogenous thrombin potential compared with subjects without MB (all p < 0.001). All CAT parameters, except for peak thrombin generation (p = 0.049), were similar in VKA patients with (n = 25, 17.2%) vs. without MBs. By logistic regression, time to start thrombin generation (p = 0.007) and unprovoked VTE (p = 0.041) independently predicted MBs on rivaroxaban. Major bleedings were more frequent in patients with MBs (17.3% vs. 1.8%, p < 0.001). Abnormal CAT parameters characterize VTE patients prone to MBs on rivaroxaban, but not on VKA. Time to start thrombin generation measured about 24 h since the last rivaroxaban dose might help predict MBs.

背景与目标： ：出血是最令人恐惧和最难以预测的抗凝不良事件。我们试图调查在静脉血栓栓塞（VTE）后抗凝患者中，校准的自动血栓成像（CAT）参数是否与轻微出血（MB）相关。入选了132例使用rivaroxaban的患者，145例使用维生素K拮抗剂（VKA）的患者和31例停止抗凝治疗的对照组。在下一次服用抗凝剂之前，我们测量了CAT参数以及利伐沙班的浓度和INR。在10个月的中位随访期间，我们记录了轻度和重度出血。在利伐沙班上，与无MB的受试者相比，27名（20.5％）的MB患者开始凝血酶的时间更长，凝血酶的峰值生成量较低，内源性凝血酶的潜能较低（所有p <0.001）。 VKA患者（n = 25，17.2％）与未使用MBs的患者相比，除凝血酶峰值峰值（p = 0.049）外，所有CAT参数均相似。通过逻辑回归，开始凝血酶生成的时间（p = 0.007）和无缘无故的VTE（p = 0.041）独立预测了利伐沙班上的MB。 MBs患者的大出血发生率更高（17.3％vs. 1.8％，p <0.001）。 CAT参数异常是在利伐沙班上VBE患者倾向于MB的特征，而在VKA上则不然。从最后一次利伐沙班剂量起大约24小时开始测量凝血酶生成的时间，可能有助于预测MB。

BACKGROUND & AIMS: RATIONALE:Data on nonvitamin K antagonist oral anticoagulant being used for the treatment of LAA thrombi are limited only in nonvalvular atrial fibrillation. There are no data on the antithrombotic efficacy and safety of nonvitamin K antagonist oral anticoagulant in the resolution of left atrial appendage (LAA) thrombi in patients with rheumatic mitral stenosis. PATIENT CONCERNS:A 49-year-old woman with known rheumatic mitral stenosis and atrial fibrillation was referred for percutaneous transvenous mitral commissurotomy because of progressive dyspnea on exertion over a period of 3 months. DIAGNOSES:Transesophageal echocardiography (TEE) demonstrated a large LAA thrombus protruding into left atria cavity before the procedure. INTERVENTIONS:Direct factor Xa (FXa) inhibitor rivaroxaban (20 mg/d) was started for the patient. After 3 weeks of rivaroxaban treatment TEE showed a relevantly decreased thrombus size, and a complete thrombus resolution was achieved after 5 weeks of anticoagulant therapy with the FXa inhibitor. OUTCOMES:To the best of our knowledge, this is the first documented case of large LAA thrombus resolution with nonvitamin K antagonist oral anticoagulant in severe mitral stenosis, and in which percutaneous transvenous mitral commissurotomy was performed subsequently. LESSONS:The report indicated that rivaroxaban could be a therapeutic option for mitral stenosis patients with LAA thrombus. Further study is required before the routine use of rivaroxaban in patients with rheumatic mitral stenosis and atrial fibrillation.

背景与目标： 理由：仅用于非瓣膜性房颤的非维生素K拮抗剂口服抗凝剂用于治疗LAA血栓的数据有限。目前尚无关于非维生素K拮抗剂口服抗凝剂对风湿性二尖瓣狭窄患者左心耳（LAA）血栓形成的抗血栓形成功效和安全性的数据。
患者担忧：一名49岁的已知风湿性二尖瓣狭窄和心房纤颤的妇女因在3个月的劳累期间进行性呼吸困难而接受经皮经皮二尖瓣合缝术。
诊断：经食道超声心动图（TEE）证实，术前有较大的LAA血栓伸入左心房腔。
干预措施：患者开始使用直接因子Xa（FXa）抑制剂利伐沙班（20 mg / d）。利伐沙班治疗3周后，TEE显示血栓大小相应减少，用FXa抑制剂进行抗凝治疗5周后，血栓完全消退。
结果：就我们所知，这是首次记录的严重二尖瓣狭窄合并非维生素K拮抗剂口服抗凝剂的大面积LAA血栓形成病例，随后进行了经皮经皮静脉二尖瓣合缝术。
经验教训：该报告指出，利伐沙班可以作为二尖瓣狭窄合并LAA血栓的患者的治疗选择。风湿性二尖瓣狭窄和房颤患者常规使用利伐沙班之前，需要进一步研究。

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： 背景与目的：评价新型抗凝药和华法林在中国房颤患者中的预防成本效益。
方法：建立马尔可夫模型以比较使用药物成本，服药后检查的成本以及其他治疗的增量成本的患者的质量调整生命年（QALYs）。将达比加群（110和150 mg，每天两次）和利伐沙班（20 mg，每天一次）与华法林（3-6 mg，每天一次）进行比较。在我们的研究中，支付意愿是2018年中国人均GDP（9481.88 $）的三倍。
结果：华法林，利伐沙班，达比加群110 mg出价和达比加群150 mg出价的总成本分别为5317.31 $，29673.33 $，23615.49 $和34324.91 $。四种干预措施的QALYs分别为11.07年，15.46年，12.4年和15年。三种新型口服抗凝药和华法林的成本效益分析表明，将利伐沙班与华法林比较时，增量成本效益比（ICER）为5548.07 $ / QALY。利伐沙班是最具成本效益的选择，而华法林则是最少的选择。
结论：在中国房颤患者中，尽管华法林价格便宜，但从经济角度考虑，利伐沙班具有更好的成本效益优势。

BACKGROUND & AIMS: OBJECTIVE:Rivaroxaban (BAY 59-7939) is an oral, direct Factor Xa (FXa) inhibitor being developed for the prevention and treatment of thromboembolic disorders. This analysis aimed to define population models for the pharmacokinetics (PK) and pharmacodynamics (PD) ofrivaroxaban in healthy males. METHODS:Non-linear, mixed-effect modeling was used to analyze rivaroxaban plasma concentration and PD data (FXa activity and clotting tests) from subjects in a phase I, multiple-ascending-dose study. Subjects received 5 mg rivaroxaban once, twice or three times daily, or 10, 20 or 30 mg rivaroxaban twice daily. RESULTS:The population PK of rivaroxaban were well described by an oral, two-compartment model with first-order absorption and elimination from the central compartment. Population mean estimates for apparent oral clearance and volume of distribution for the central compartment were 9.2 1/h and 55 1, respectively, with moderate inter-individual variability (17.4% and 30.7%, respectively). Total volume of distribution for rivaroxaban at steady state was approximately 70 1. Residual (unexplained) variability was 25%. FXa activity correlated with rivaroxaban plasma concentrations following an inhibitory Emax model; prothrombin time (PT) and rivaroxaban plasma concentrations correlated with a linear model, with a slope of 4.6 s/(100 microg/1). Inter-individual variability was low for the correlation with PT. The models derived were used to define sampling windows for population PK/PD modeling in Phase II studies. CONCLUSIONS:This analysis confirms that rivaroxaban has predictable, dose-proportional PK and PD. The linear correlation between rivaroxaban plasma concentrations and PT suggests that this test might be useful to assess rivaroxaban exposure in patients, if required.

背景与目标： 目的：Rivaroxaban（BAY 59-7939）是一种口服直接Xa因子（FXa）抑制剂，正在开发用于预防和治疗血栓栓塞性疾病。该分析旨在为健康男性中的利伐沙班的药代动力学（PK）和药效动力学（PD）定义种群模型。
方法：在第一阶段多剂量研究中，非线性混合效应模型用于分析利伐沙班的血浆浓度和PD数据（FXa活性和凝结试验）。受试者每天一次，两次或三次接受5毫克rivaroxaban，或每天两次接受10、20或30毫克rivaroxaban。
结果：利伐沙班的种群PK通过口服，两室模型被很好地描述，该模型具有一阶吸收和从中央室消除的作用。中央隔室的表观口腔清洁度和分布体积的总体平均估计分别为9.2 1 / h和55 1，个体之间的差异性中等（分别为17.4％和30.7％）。利伐沙班在稳定状态下的总分配量约为70 1.残余（无法解释的）变异性为25％。在抑制性Emax模型下，FXa活性与利伐沙班血浆浓度相关。凝血酶原时间（PT）和利伐沙班血浆浓度与线性模型相关，斜率为4.6 s /（100 microg / 1）。与PT的相关性，个体间变异性较低。在第二阶段研究中，使用导出的模型来定义用于人口PK / PD建模的采样窗口。
结论：该分析证实利伐沙班具有可预测的，与剂量成比例的PK和PD。利伐沙班血浆浓度与PT之间的线性相关性表明，如果需要的话，该试验对于评估利伐沙班患者的暴露可能是有用的。

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： 重要性：达比加群和利伐沙班是经批准用于非瓣膜性房颤（AF）患者的中风预防的非维生素K口服抗凝剂。这些药物在中风，出血或死亡率方面没有随机的头对头比较。
目的：比较开始使用达比加群或利伐沙班治疗的非瓣膜性房颤患者的血栓栓塞性中风，颅内出血（ICH），主要颅外出血（包括主要胃肠道出血）和死亡率的风险。
设计，背景和参与者：2011年11月对118891名65岁以上老年非瓣膜性房颤患者进行回顾性新使用者队列研究，参加了有偿服务的Medicare，并从2011年11月4日开始使用达比加群或利伐沙班治疗，直到2014年6月30日为止。基线特征的差异是根据倾向得分，使用稳定的治疗权重的逆概率进行调整的。数据分析的时间为2015年5月7日至2016年6月30日。
暴露：达比加群150毫克，每日两次；利伐沙班，20毫克，每天一次。
主要结果和措施：以达比加群为参考，对血栓栓塞性中风，ICH，主要颅外出血（包括主要胃肠道出血）和死亡率的主要结局调整后的危险比（HRs）。还估计了调整后的发病率差异（AIRD）。
结果：总共有52240例达比加群治疗和66651例利伐沙班治疗的患者（女性占47％）分别进行了15524和20199人年的治疗随访，其中发生了2537例主要预后事件。利伐沙班的使用与血栓栓塞性卒中的统计学上无统计学意义的降低（HR，0.81； 95％CI，0.65-1.01； P = .07； AIRD = 1.8病例/ 1000人-年）相比，ICH的统计学显着增加（HR， 1.65; 95％CI，1.20-2.26; P = .002; AIRD = 2.3超标病例/ 1000人年）和严重颅外出血（HR，1.48; 95％CI，1.32-1.67; P <.001; AIRD =每1 000人年增加13.0例），包括主要胃肠道出血（HR，1.40; 95％CI，1.23-1.59; P <.001; AIRD = 9.4超病情况/ 1000人年），且统计上无显着增加死亡率（HR，1.15； 95％CI，1.00-1.32； P = .051； AIRD = excess3.1超重病例/ 1000人年）。在75岁或以上或CHADS2评分大于2的患者中，与达比加群相比，利伐沙班的使用与死亡率显着增加有关。使用利伐沙班的ICH过量率超过了其降低的血栓栓塞性卒中率。
结论与相关性：与每日两次两次达比加群150 mg相比，每日一次利伐沙班20 mg治疗与ICH和主要颅外出血（包括主要胃肠道出血）的统计学显着增加相关。

BACKGROUND & AIMS: Importance:The COMPASS (Cardiovascular Outcomes for People Using Anticoagulation Strategies) randomized clinical trial was stopped early owing to the efficacy of low-dose rivaroxaban plus aspirin in preventing major cardiovascular events. The main reason for early trial termination was the effect of combination therapy on reducing ischemic strokes. Objective:To analyze the association between low-dose rivaroxaban with or without aspirin and different ischemic stroke subtypes. Design, Setting, and Participants:This is a secondary analysis of a multicenter, double-blind, randomized, placebo-controlled study that was performed in 33 countries from March 12, 2013, to May 10, 2016. Patients with stable atherosclerotic vascular disease were eligible, and a total of 27 395 participants were randomized and followed up to February 6, 2017. All first ischemic strokes and uncertain strokes that occurred by this date were adjudicated using TOAST (Trial of Org 10172 in Acute Stroke Treatment) criteria. The analysis of ischemic stroke subtypes was evaluated using an intention-to-treat principle. Statistical analysis was performed from March 12, 2013, to February 6, 2017. Interventions:Participants received rivaroxaban (2.5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban (5 mg twice a day), or aspirin (100 mg once a day). Main Outcomes and Measures:Risk of ischemic stroke subtypes during follow-up. Results:A total of 291 patients (66 women; mean [SD] age, 69.4 [8.5] years; 43 [14.8%] had a previous nonlacunar stroke) experienced an ischemic stroke. During the study, 49 patients (16.8%) received a diagnosis of atrial fibrillation. Applying TOAST criteria, 59 strokes (20.3%) were cardioembolic, 54 strokes (18.6%) were secondary to greater than 50% stenosis of the ipsilateral internal carotid artery, 42 strokes (14.4%) had a negative evaluation that met criteria for embolic stroke of undetermined source, and 21 strokes (7.2%) were secondary to small vessel disease. There were significantly fewer cardioembolic strokes (hazard ratio [HR], 0.40 [95% CI, 0.20-0.78]; P = .005) and embolic strokes of undetermined source (HR, 0.30 [95% CI, 0.12-0.74]; P = .006) in the combination therapy group compared with the aspirin-only group. A trend for reduction in strokes secondary to small vessel disease (HR, 0.36 [95% CI, 0.12-1.14]; P = .07) was not statistically significant. No significant difference was observed between the 2 groups in strokes secondary to greater than 50% carotid artery stenosis (HR, 0.85 [95% CI, 0.45-1.60]; P = .61). Rivaroxaban, 5 mg, twice daily showed a trend for reducing cardioembolic strokes compared with aspirin (HR, 0.57 [95% CI, 0.31-1.03]; P = .06) but was not associated with reducing other stroke subtypes. Conclusions and Relevance:For patients with systemic atherosclerosis, low-dose rivaroxaban plus aspirin was associated with large, significant reductions in cardioembolic strokes and embolic strokes of undetermined source. However, these results of exploratory analysis need to be independently confirmed before influencing clinical practice. Trial Registration:ClinicalTrials.gov identifier: NCT01776424.

背景与目标： 重要性：由于低剂量利伐沙班加阿司匹林在预防重大心血管事件中的功效，COMPASS（使用抗凝策略的人的心血管结局）随机临床试验已提前停止。提前终止试验的主要原因是联合治疗对减少缺血性卒中的作用。
目的：分析有或没有阿司匹林的低剂量利伐沙班与不同缺血性中风亚型的相关性。
设计，背景和参与者：这是一项多中心，双盲，随机，安慰剂对照研究的二次分析，该研究于2013年3月12日至2016年5月10日在33个国家/地区进行。稳定的动脉粥样硬化性血管疾病患者符合条件，共有27395名参与者被随机分组​​，并随访至2017年2月6日。使用TOAST（急性卒中治疗中的组织10172试验）对截至该日期发生的所有首次缺血性卒中和不确定性卒中进行判定。缺血性中风亚型的分析使用意向性治疗原则进行评估。从2013年3月12日至2017年2月6日进行统计分析。
干预措施：参与者接受利伐沙班（每天两次2.5毫克）加阿司匹林（每天一次100毫克），利伐沙班（每天两次5毫克）或阿司匹林（每天一次100毫克）。
主要结果和措施：随访期间缺血性中风亚型的风险。
结果：总共291例患者发生了缺血性中风（66名女性；平均[SD]年龄为69.4 [8.5]岁； 43名[14.8％]患有先前的非腔隙性中风）。在研究过程中，有49位患者（16.8％）被诊断为房颤。采用TOAST标准，心脏栓塞59例（20.3％），同侧颈内动脉狭窄大于50％继发54例（18.6％），符合栓塞性中风标准的阴性评估为42例（14.4％）来源不明，其中21例（7.2％）中风是继发于小血管疾病。心脏栓塞卒中（危险比[HR]，0.40 [95％CI，0.20-0.78]； P = .005）和未确定来源的栓塞卒中（HR，0.30 [95％CI，0.12-0.74]； P与单纯阿司匹林组相比，联合治疗组==。006）。继发于小血管疾病的卒中减少的趋势（HR，0.36 [95％CI，0.12-1.14]； P = .07）没有统计学意义。在颈动脉狭窄大于50％的继发卒中中，两组之间未观察到显着差异（HR，0.85 [95％CI，0.45-1.60]； P = 61）。与阿司匹林（HR，0.57 [95％CI，0.31-1.03]； P = .06）相比，每日两次5 mg利伐沙班有降低心脏栓塞性中风的趋势，但与减少其他中风亚型无关。
结论和相关性：对于系统性动脉粥样硬化患者，低剂量利伐沙班加阿司匹林可显着减少心脏栓塞性卒中和未确定来源的栓塞性卒中。但是，探索性分析的这些结果需要在影响临床实践之前进行独立确认。
试用注册：ClinicalTrials.gov标识符：NCT01776424。

BACKGROUND & AIMS: :Rivaroxaban has been found to be noninferior to warfarin for preventing stroke or systemic embolism in patients with high-risk atrial fibrillation (AF) and is associated with a lower rate of intracranial hemorrhage. To assess the cost-effectiveness of rivaroxaban compared to adjusted-dose warfarin for the prevention of stroke in patients with AF, we built a Markov model using a United States payer/Medicare perspective and a lifetime time horizon. The base-case analysis assumed a cohort of patients with AF 65 years of age with a congestive heart failure, hypertension, age, diabetes, stroke (2 points) score of 3 and no contraindications to anticoagulation. Data sources included the Rivaroxaban Once-daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET-AF) and other studies of anticoagulation. Outcome measurements included costs in 2011 United States dollars, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios (ICERs). Patients with AF treated with rivaroxaban lived an average of 10.03 QALYs at a lifetime treatment cost of $94,456. Those receiving warfarin lived an average of 9.81 QALYs and incurred costs of $88,544. The ICER for rivaroxaban was $27,498 per QALY. These results were most sensitive to changes in the hazard decrease of intracranial hemorrhage and stroke with rivaroxaban, cost of rivaroxaban, and time horizon. Monte Carlo simulation demonstrated rivaroxaban was cost-effective in 80% and 91% of 10,000 iterations at willingness-to-pay thresholds of $50,000 and $100,000 per QALY, respectively. In conclusion, this Markov model suggests that rivaroxaban therapy may be a cost-effective alternative to adjusted-dose warfarin for stroke prevention in AF.

背景与目标： Rivaroxaban被认为在预防高危房颤（AF）患者中风或全身性栓塞方面不逊于华法林，并且与颅内出血发生率较低相关。为了评估利伐沙班与调整剂量华法林相比预防房颤患者卒中的成本效益，我们使用美国付款人/医疗保险的观点和终生时间范围建立了马尔可夫模型。基本病例分析假设一组年龄在65岁以下的房颤患者，其充血性心力衰竭，高血压，年龄，糖尿病，中风（2分）得分为3，无抗凝禁忌症。数据来源包括利伐沙班每日一次口服直接因子Xa抑制与房颤中风和栓塞试验的维生素K拮抗作用比较（ROCKET-AF）以及其他抗凝研究。成果衡量标准包括2011年的美元成本，质量调整生命年（QALY）和增量成本效益比（ICER）。利伐沙班治疗的房颤患者平均生活10.03 QALYs，终生治疗费用为94,456美元。那些接受华法林治疗的患者平均生活了9.81个QALYs，费用为88,544美元。利伐沙班的ICER为每QALY 27,498美元。这些结果对利伐沙班引起的颅内出血和中风的危险性降低，利伐沙班的花费和时间跨度的变化最为敏感。蒙特卡洛模拟显示，利伐沙班在10,000次迭代的80％和91％的成本效益阈值分别为每QALY 50,000美元和100,000美元。总之，该马尔可夫模型表明，利伐沙班治疗可能是一种替代成本合理的华法林的经济有效替代方案，可用于预防房颤。

BACKGROUND & AIMS: :This study aimed to compare the efficacy and safety of aspirin, rivaroxaban and low-molecular-weight heparin (LMWH) for post total knee arthroplasty (TKA) deep vein thrombosis (DVT) prophylaxis. Between July 2011 and July 2013, a prospective randomized controlled trial was performed on 324 patients with osteoarthritis who underwent primary unilateral TKA. Twelve hours after the surgery, Group A was given oral rivaroxaban at a dose of 10 mg/day. Group B was given subcutaneous LMWH at a dose of 4000 AxaIU (0.4 ml)/day and Group C was given oral aspirin at a dose of 100 mg/day. All three groups were treated for 14 days, and all of the patients were followed for 4 weeks. The incidence of DVT, dominant/hidden blood loss, the incidence of wound complications and the incidence of subcutaneous ecchymosis in the affected extremities were compared between the three groups. The incidence of DVT was lower in Group A compared with the other two groups [3 (2.94%) vs. 14 (12.50%), P = 0.029; 3 (2.94%) vs. 18 (16.36%), P = 0.017]. However, hidden blood loss [1.71 (1.19-2.97) vs. 1.18 (0.77-2.31), P = 0.009; 1.71 (1.19-2.97) vs. 1.30 (0.61-2.43), P = 0.004] and wound complications [5 (4.90) vs. 3 (2.67), P = 0.027; 5 (4.90) vs. 2 (1.82), P = 0.014] were more common in Group A than in the other groups. There were no significant differences between Group B and Group C in the incidence of DVT [14 (12.50%) vs. 18 (16.36%), P = 0.831], hidden blood loss [1.18 (0.77-2.31) vs. 1.30 (0.61-2.43), P = 0.327] or wound complications [3 (2.67) vs. 2 (1.82), P = 0.209]. No significant differences in the incidence of limb swelling were found between the three groups [38 (37.25%) vs. 28 (25.00%) vs. 24 (21.82%), P = 0.247]. Group A had a higher incidence of subcutaneous ecchymosis in the affected extremities than Group C [74 (72.55%) vs. 54 (49.09%), P = 0.039], but there were no significant differences between Groups A and B [74 (72.55%) vs. 62 (55.36%), P = 0.193] or between Groups B and C [62 (55.36%) vs. 54 (49.09%), P = 0.427]. Rivaroxaban has a positive anticoagulation effect but leads to increases in both postoperative blood loss and wound complications in patients. Hence, clinicians using rivaroxaban for anticoagulant therapy should closely monitor the changes in the hemoglobin level and wound healing and promptly supplement blood volume and provide other symptomatic and supportive treatments. No significant difference in post-TKA DVT prophylaxis was found between aspirin and LMWH, and the former can be used as part of a multimodal anticoagulation therapy.

背景与目标： ：本研究旨在比较阿司匹林，利伐沙班和低分子量肝素（LMWH）在全膝关节置换术后（TKA）预防深静脉血栓形成（DVT）的有效性和安全性。在2011年7月至2013年7月之间，对324例行原发性单侧TKA的骨关节炎患者进行了一项前瞻性随机对照试验。手术后十二小时，给A组口服利伐沙班口服，剂量为10μg/天。 B组给予皮下注射LMWH，剂量为4000 AxaIU（0.4μml）/天，C组给予口服阿司匹林，剂量为100μgIU/天。三组均治疗14天，所有患者均随访4周。比较了三组患肢的DVT发生率，显性/隐性失血，伤口并发症的发生率和皮下瘀斑的发生率。与其他两组相比，A组的DVT发生率较低[3（2.94％）vs. 14（12.50％），P = 0.029; 3（2.94％）对18（16.36％），P = 0.017]。然而，隐性失血[1.71（1.19-2.97）对1.18（0.77-2.31），P = 0.009； 1.71（1.19-2.97）对1.30（0.61-2.43），P = 0.004]和伤口并发症[5（4.90）对3（2.67），P = 0.027； A组中5（4.90）vs. 2（1.82），P2 = 0.014]比其他组更常见。 B组和C组之间DVT的发生率无显着差异[14（12.50％）vs. 18（16.36％），P = 0.831]，隐性失血[1.18（0.77-2.31）vs.1.30（0.61） -2.43），P = 0.327]或伤口并发症[3（2.67）对2（1.82），P = 0.209]。三组之间肢体肿胀的发生率没有显着差异[38（37.25％）vs. 28（25.00％）vs. 24（21.82％），P = 0.247]。 A组患肢皮下瘀斑的发生率高于C组[74（72.55％）vs. 54（49.09％），P = 0.039]，但A组和B组之间无显着差异[74（72.55） ％）vs. 62（55.36％），P = 0.193]或在B组和C组之间[62（55.36％）vs. 54（49.09％），P = 0.427]。利伐沙班具有积极的抗凝作用，但会导致术后失血量增加和患者伤口并发症增加。因此，使用利伐沙班进行抗凝治疗的临床医生应密切监测血红蛋白水平和伤口愈合的变化，并迅速补充血容量并提供其他对症和支持治疗。阿司匹林和LMWH在TKA预防DVT预防方面无显着差异，前者可作为多模式抗凝治疗的一部分。

BACKGROUND & AIMS: BACKGROUND:Standard therapy for cancer-associated venous thromboembolism (VTE) is low-molecular-weight heparin. The use of direct oral anticoagulants for cancer-associated VTE has increased; however, their efficacy and safety in lung cancer patients remain unclear. OBJECTIVES:We examined the efficacy and safety of rivaroxaban compared with dalteparin for cancer-associated VTE in patients with primary lung cancer. METHODS:A single-center retrospective study of 204 patients with primary lung cancer who were prescribed rivaroxaban (n = 131) or dalteparin (n = 73) for VTE was performed. The primary endpoint was a composite event including recurrence and major or clinically relevant nonmajor bleeding. Secondary endpoints included the incidence of recurrence, major and clinically relevant nonmajor bleeding, all-cause mortality, and bleeding or pulmonary embolism-related mortality. RESULTS:The composite event occurred in 38 (29.0) and 12 (16.4%) patients in the rivaroxaban and dalteparin (p = 0.045) groups, respectively. The multivariate Cox proportional hazards model for age, Eastern Cooperative Oncology Group performance score, and bleeding risk factors revealed the rivaroxaban group showed a 1.176-fold composite event risk without statistical significance (0.595-2.324, p = 0.641). There was no statistically significant intergroup difference for the incidence of VTE recurrence (5.3% in the rivaroxaban group versus 2.7% in the dalteparin group, p = 0.495) and major or clinically relevant nonmajor bleeding (23.7% in the rivaroxaban group versus 13.7% in the dalteparin group, p = 0.089). There was no significant difference in the all-cause mortality rate (hazard ratio 0.864, 95% CI 0.624-1.196, p = 0.337). CONCLUSIONS:There was no difference in the safety and efficacy profile of rivaroxaban compared with dalteparin. Therefore, rivaroxaban may be a valuable treatment option for lung cancer-associated VTE.

背景与目标： 背景：癌症相关的静脉血栓栓塞症（VTE）的标准疗法是低分子量肝素。直接口服抗凝剂用于与癌症相关的VTE的使用有所增加；然而，它们在肺癌患者中的疗效和安全性尚不清楚。
目的：我们研究了利伐沙班与达肝素相比对原发性肺癌患者与癌症相关的VTE的有效性和安全性。
方法：对204例原发性肺癌患者进行单中心回顾性研究，他们接受利伐沙班（n = 131）或达肝素（n = 73）的VTE处方。主要终点为复合事件，包括复发和重大或临床相关的非重大出血。次要终点包括复发率，重大和临床相关的非重大出血，全因死亡率以及与出血或肺栓塞相关的死亡率。
结果：利伐沙班和达肝素（p = 0.045）组分别发生38例（29.0）和12例（16.4％）患者的复合事件。年龄，东部合作肿瘤小组表现评分和出血危险因素的多变量Cox比例风险模型显示，利伐沙班组的复合事件风险为1.176倍，无统计学意义（0.595-2.324，p = 0.641）。 VTE复发的发生率在两组间均无统计学差异（利伐沙班组为5.3％，达肝素组为2.7％，p = 0.495）以及重大或临床相关的非重大出血（利伐沙班组为23.7％，而利伐沙班组为13.7％）。达肝素组，p = 0.089）。全因死亡率没有显着差异（危险比0.864，95％CI 0.624-1.196，p = 0.337）。
结论：利伐沙班与达肝素相比，安全性和疗效无差异。因此，利伐沙班可能是与肺癌相关的VTE的一种有价值的治疗选择。

BACKGROUND & AIMS: BACKGROUND:Novel anticoagulations (NOACs) are increasingly prescribed for the prevention of stroke in premenopausal women with atrial fibrillation. Small studies suggest NOACs are associated with a higher risk of abnormal uterine bleeds than vitamin K antagonists (VKAs). Because there is no direct empirical evidence on the benefit/risk profile of rivaroxaban compared to VKAs in this subgroup, we synthesize available indirect evidence, estimate decision uncertainty on the treatments, and assess whether further research in premenopausal women is warranted. METHODS:A Markov model with annual cycles and a lifetime horizon was developed comparing rivaroxaban (the most frequently prescribed NOAC in this population) and VKAs. Clinical event rates, associated quality adjusted life years, and health care costs were obtained from different sources and adjusted for gender, age, and history of stroke. A Monte Carlo simulation with 10,000 iterations was then performed for a hypothetical cohort of premenopausal women, estimated to be reflective of the population of premenopausal women with AF in The Netherlands. RESULTS:In the simulation, rivaroxaban is the better treatment option for the prevention of ischemic strokes in premenopausal women in 61% of the iterations. Similarly, this is 98% for intracranial hemorrhages, 24% for major abnormal uterine bleeds, 1% for minor abnormal uterine bleeds, 9% for other major extracranial hemorrhages, and 23% for other minor extracranial hemorrhages. There is a 78% chance that rivaroxaban offers the most quality-adjusted life years. The expected value of perfect information in The Netherlands equals 122 quality-adjusted life years and 22 million Euros. CONCLUSIONS:There is a 22% risk that rivaroxaban offers a worse rather than a better benefit/risk profile than vitamin K antagonists in premenopausal women. Although rivaroxaban is preferred over VKAs in this population, further research is warranted, and should preferably take the shape of an internationally coordinated registry study including other NOACs.

背景与目标： 背景：为预防绝经前患有房颤的女性中风，越来越多地采用新型抗凝剂（NOAC）。小型研究表明，与维生素K拮抗剂（VKA）相比，NOAC与异常子宫出血的风险更高。由于在该亚组中尚无关于利伐沙班与VKA相比获益/风险概况的直接经验证据，因此我们综合了可用的间接证据，估计了治疗的决策不确定性，并评估了是否有必要对绝经前妇女进行进一步研究。
方法：比较了利伐沙班（该人群中最常开处方的NOAC）和VKA，建立了一个具有年度周期和寿命范围的马尔可夫模型。从不同来源获得临床事件发生率，相关的质量调整生命年和医疗保健费用，并对性别，年龄和中风病史进行调整。然后，对假设的绝经前女性队列进行了10,000次迭代的Monte Carlo模拟，估计该群体反映了荷兰的AF绝经前女性人群。
结果：在模拟中，在61％的迭代中，利伐沙班是预防绝经前女性缺血性卒中的较好治疗选择。同样，颅内出血为98％，严重异常子宫出血为24％，轻度异常子宫出血为1％，其他重大颅外出血为9％，其他轻度颅外出血为23％。利伐沙班有78％的机会提供最优质的生命周期。在荷兰，完美信息的预期价值相当于122个质量调整的生命年和2200万欧元。
结论：在绝经前妇女中，利伐沙班比维生素K拮抗剂提供更差的益处/风险比有22％的风险。尽管在该人群中利伐沙班优于VKA，但有必要进行进一步的研究，并应采用国际协调的注册研究形式，包括其他NOAC。

BACKGROUND & AIMS: :We investigated three-month clinical outcomes in patients with venous thromboembolism (VTE) treated with rivaroxaban or conventional anticoagulation in routine clinical practice. Between November 2012 and February 2015, 2,062 consecutive patients with VTE from 11 acute care hospitals in Switzerland were enrolled in the SWIss Venous ThromboEmbolism Registry (SWIVTER). Overall, 417 (20 %) patients were treated with rivaroxaban. In comparison to 1,645 patients on conventional anticoagulation, patients on rivaroxaban were younger (56 ± 18 vs. 65 ± 17 years; p<0.001), less often had pulmonary embolism (38 % vs 66 %; p<0.001), hypertension (26 % vs 41 %; p<0.001), cancer (10 % vs 28 %; p<0.001), congestive heart failure (10 % vs 17 %; p=0.001), diabetes (8 % vs 15 %; p<0.001), chronic lung disease (7 % vs 13 %; p=0.001), renal insufficiency (7 % vs 13 %; p=0.001), recent surgery (7 % vs 14 %; p<0.001), and acute coronary syndrome (1 % vs 4 %; p=0.009). VTE reperfusion therapy was more frequently used (28 % vs 9 %; p<0.001) and indefinite-duration anticoagulation treatment less often planned (26 % vs 39 %; p<0.001), respectively. In the propensity score-adjusted population, the risk of recurrent VTE was similar in patients on rivaroxaban vs conventional anticoagulation (1.2 % vs 2.1 %, hazard ratio [HR] 0.55, 95 % confidence interval [CI] 0.18-1.65; p=0.29); the risk of major bleeding was also similar, respectively (0.5 % vs 0.5 %, HR 1.00, 95 %CI 0.14-7.07; p=1.00). Conventional anticoagulation is still frequently used for the treatment of VTE, particularly in the elderly and those with comorbidities. Early clinical outcomes were comparable between propensity score-adjusted patient populations on rivaroxaban and conventional anticoagulation.

背景与目标： ：我们在常规临床实践中研究了利伐沙班或常规抗凝治疗的静脉血栓栓塞症（VTE）患者三个月的临床结局。在2012年11月至2015年2月之间，来自瑞士11所急诊医院的2,062例VTE连续患者被纳入SWIs静脉血栓栓塞注册表（SWIVTER）。总体上，有417（20％）的患者接受了利伐沙班治疗。与1,645例接受常规抗凝治疗的患者相比，利伐沙班的患者更年轻（56±18 vs. 65±17岁； p <0.001），发生肺栓塞的频率更低（38 %% vs 66 %%； p <0.001），高血压（26岁） ％vs 41％; p <0.001），癌症（10％vs 28％; p <0.001），充血性心力衰竭（10％vs 17％; p = 0.001），糖尿病（8％vs 15％; p <0.001） ，慢性肺部疾病（7 %% vs 13％; p = 0.001），肾功能不全（7 %% vs 13;％; p = 0.001），近期手术（7 %% vs 14％; p <0.001）和急性冠脉综合征（1 ％vs 4％； p = 0.009）。 VTE再灌注疗法的使用频率更高（分别为28％和9％； p <0.001）和不定期的抗凝治疗（计划百分比分别为26％和39％； p <0.001）。在按倾向评分调整的人群中，利伐沙班与常规抗凝治疗的患者再次发生VTE的风险相似（1.2 %% vs 2.1 %%，危险比[HR] 0.55，95 %%置信区间[CI] 0.18-1.65； p = 0.29 ）;大出血的风险也分别相似（0.5 %% vs.0.5 %%，HR 1.00，95 %% CI 0.14-7.07； p = 1.00）。传统的抗凝治疗仍经常用于VTE的治疗，尤其是在老年人和合并症患者中。利伐沙班和常规抗凝治疗的倾向评分调整后的患者人群之间的早期临床结果具有可比性。

BACKGROUND & AIMS: :Post-thrombotic syndrome (PTS) is a common complication of deep-vein thrombosis (DVT). Poor quality treatment with vitamin K antagonists (VKA) is a risk factor for PTS. We hypothesised that treatment with the direct oral anticoagulant (DOAC) rivaroxaban may lower PTS incidence as compared to enoxaparin/VKA, as DOACs have a more stable pharmacologic profile than VKA. We performed a post-hoc subgroup analysis of the Einstein DVT trial (n=3449). Kaplan-Meier survival analysis was performed to compare the cumulative incidence of PTS between the rivaroxaban and enoxaparin/VKA groups. Hazard ratios (HR) and 95 % confidence intervals (CI) were calculated using Cox proportional hazards models. We included 336 patients with a mean age of 58 ± 16 years and a median follow-up after index DVT of 57 months (interquartile range 48-64). Of these, 162 (48 %) had been treated with rivaroxaban and 174 (52 %) with enoxaparin/VKA. The cumulative PTS incidence at 60 months follow-up was 29 % in the rivaroxaban group and 40 % in the enoxaparin/VKA group. After adjusting for age, gender, body mass index, previous VTE, ipsilateral recurrent DVT, extent of DVT, idiopathic DVT, duration of anticoagulant treatment, compliance to assigned study medication, elastic compression stocking use and active malignancy, the HR of PTS development for rivaroxaban was 0.76 (95 % CI: 0.51-1.13). In conclusion, treatment of acute DVT with rivaroxaban was associated with a numerically lower but statistically non-significant risk of PTS compared to enoxaparin/VKA treatment. The potential effect on reducing PTS deserves evaluation in a large randomised trial.

背景与目标： ：血栓后综合症（PTS）是深静脉血栓形成（DVT）的常见并发症。维生素K拮抗剂（VKA）的治疗质量差是PTS的危险因素。我们假设与依诺肝素/ VKA相比，直接口服抗凝剂（DOAC）利伐沙班治疗可降低PTS发生率，因为DOACs的药理作用比VKA更稳定。我们对爱因斯坦DVT试验（n = 3449）进行了事后亚组分析。进行Kaplan-Meier生存分析以比较利伐沙班和依诺肝素/ VKA组之间PTS的累积发生率。使用Cox比例风险模型计算危害比（HR）和95）％置信区间（CI）。我们纳入了336例平均年龄58±16岁，DVT指数中位数为57个月（四分位间距48-64）的中位随访患者。其中162例（48％）已用利伐沙班治疗，174例（52％）已用依诺肝素/ VKA治疗。利伐沙班组在60个月随访时的累积PTS发生率为29％，依诺肝素/ VKA组为40％。在调整了年龄，性别，体重指数，先前的VTE，同侧复发性DVT，DVT的程度，特发性DVT，抗凝治疗的持续时间，对指定研究药物的依从性，弹性压缩袜的使用和活动性恶性肿瘤，PTS发育的HR之后利伐沙班为0.76（95％CI：0.51-1.13）。总之，与依诺肝素/ VKA治疗相比，利伐沙班治疗急性DVT与PTS的风险数值较低，但在统计学上无统计学意义。减少PTS的潜在影响值得在一项大型随机试验中进行评估。

BACKGROUND & AIMS: BACKGROUND:Rivaroxaban, a direct factor Xa inhibitor, has seldom been used in patients with coronary artery disease. In this analysis, we aimed to systematically compare the efficacy and safety of rivaroxaban in addition to the anti-platelet regimen in patients with coronary artery disease. METHODS:Online databases (MEDLINE, EMBASE, Cochrane database, www.ClinicalTrials.gov and Google scholar were searched for randomized controlled trials which were exclusively based on patients with coronary artery disease; and which compared efficacy (cardiovascular outcomes) and safety (bleeding outcomes) outcomes with the addition of rivaroxaban to the other anti-platelet agents. Analysis was carried out by the RevMan 5.3 software whereby odds ratios (OR) and 95% confidence intervals (CI) were generated following data input. RESULTS:Four trials with a total number of 40,148 patients were included (23,231 participants were treated with rivaroxaban whereas 16,919 participants were treated with placebo) in this analysis. Patients' enrollment period varied from years 2006 to 2016. The current results showed addition of rivaroxaban to significantly lower composite endpoints (OR: 0.81, 95% CI: 0.74-0.88; P = 0.00001). In addition, all-cause death, cardiac death, myocardial infarction, and stent thrombosis were also significantly reduced (OR: 0.82, 95% CI: 0.72-0.92; P = 0.0009), (OR: 0.80, 95% CI: 0.69-0.92; P = 0.002), (OR: 0.87, 95% CI: 0.77-0.98; P = 0.03) and (OR: 0.73, 95% CI: 0.55-0.97; P = 0.03) respectively. However, stroke was not significantly different. However, TIMI defined minor and major bleeding were significantly higher with rivaroxaban (OR: 2.27, 95% CI: 1.47-3.49; P = 0.0002) and (OR: 3.44, 95% CI: 1.13-10.52; P = 0.03) respectively. In addition, intracranial hemorrhage and bleeding which was defined according to the International Society on Thrombosis and Hemostasis criteria were also significantly higher with rivaroxaban (OR: 1.63, 95% CI: 1.04-2.56; P = 0.03) and (OR: 1.80, 95% CI: 1.45-2.22; P = 0.00001) respectively. Nevertheless, fatal bleeding was not significantly different. CONCLUSIONS:Addition of rivaroxaban to the anti-platelet regimen was effective in patients with coronary artery disease, but the safety outcomes were doubtful. Further future trials will be able to completely solve this issue.

背景与目标： 背景：Rivaroxaban是一种直接的Xa抑制剂，很少用于冠心病患者。在这项分析中，我们旨在系统比较利伐沙班和抗血小板方案对冠心病患者的疗效和安全性。
方法：搜索在线数据库（MEDLINE，EMBASE，Cochrane数据库，www.ClinicalTrials.gov和Google Scholar），以仅基于冠心病患者的随机对照试验进行比较，并比较疗效（心血管结局）和安全性（出血结局）通过在其他抗血小板药物中添加利伐沙班来获得结果。RevMan 5.3软件进行了分析，输入数据后得出了比值比（OR）和95％置信区间（CI）。
结果：本研究共纳入四项试验，共40,148例患者（23,231名参与者接受了利伐沙班治疗，而16,919名参与者接受了安慰剂治疗）。患者的入组时间从2006年到2016年不等。当前结果显示，加入利伐沙班可显着降低复合终点（OR：0.81，95％CI：0.74-0.88； P = 0.00001）。此外，全因死亡，心源性死亡，心肌梗塞和支架内血栓形成也显着降低（OR：0.82，95％CI：0.72-0.92； P = 0.0009），（OR：0.80，95％CI：0.69- 0.92； P ＝ 0.002），（OR：0.87，95％CI：0.77-0.98； P ＝ 0.03）和（OR：0.73，95％CI：0.55-0.97； P ＝ 0.03）。但是，中风并没有显着差异。但是，TIMI定义的利伐沙班的轻微和主要出血明显更高（OR：2.27，95％CI：1.47-3.49； P = 0.0002）和（OR：3.44，95％CI：1.13-10.52； P = 0.03）。此外，使用利伐沙班治疗时，根据国际血栓形成和止血标准定义的颅内出血和出血也明显更高（OR：1.63，95％CI：1.04-2.56； P = 0.03）和（OR：1.80，95 ％CI：1.45-2.22； P ＝ 0.00001）。然而，致命出血并没有显着差异。
结论：在抗血小板方案中加用利伐沙班对冠心病患者有效，但安全性结果值得怀疑。将来的进一步试验将能够完全解决该问题。