• 【使用阿哌沙班或维生素k拮抗剂治疗的非瓣膜性房颤患者的患者特征和出血事件: 来自意大利行政数据库的真实证据.】 复制标题 收藏 收藏
    DOI:10.2217/cer-2018-0054 复制DOI
    作者列表:Ramagopalan S,Allan V,Saragoni S,Esposti LD,Alessandrini D,Perrone V,Buda S,Stynes G,Toma C,DeSolda F,a LHUs group.
    BACKGROUND & AIMS: AIM:This study aimed to evaluate the risk of major bleeding among two cohorts of nonvalvular atrial fibrillation patients newly initiating a vitamin K antagonist (VKA) or apixaban in a real-world setting in Italy. PATIENTS & METHODS:A retrospective study using a large administrative database of Italian local health units was performed, using data from ten local health units and patients were included from the date of new initiation of apixaban or VKAs from January 2012 to June 2015. RESULTS:Risk of major bleeding was calculated using an adjusted Cox regression model. Compared with VKA, apixaban had a significantly lower risk of major bleeding (hazard ratio = 0.44 [95% CI: 0.12-0.97]). CONCLUSION:In this analysis, apixaban was associated with a lower risk of major bleeding compared with VKA.
    背景与目标:
  • 【新型冠状病毒肺炎的抗凝: 依诺肝素、肝素和阿哌沙班对死亡率的影响。】 复制标题 收藏 收藏
    DOI:10.1055/s-0040-1720978 复制DOI
    作者列表:Billett HH,Reyes-Gil M,Szymanski J,Ikemura K,Stahl LR,Lo Y,Rahman S,Gonzalez-Lugo JD,Kushnir M,Barouqa M,Golestaneh L,Bellin E
    BACKGROUND & AIMS: BACKGROUND: Mortality in coronavirus disease of 2019 (COVID-19) is associated with increases in prothrombotic parameters, particularly D-dimer levels. Anticoagulation has been proposed as therapy to decrease mortality, often adjusted for illness severity. OBJECTIVE: We wanted to investigate whether anticoagulation improves survival in COVID-19 and if this improvement in survival is associated with disease severity. METHODS: This is a cohort study simulating an intention-to-treat clinical trial, by analyzing the effect on mortality of anticoagulation therapy chosen in the first 48 hours of hospitalization. We analyzed 3,625 COVID-19+ inpatients, controlling for age, gender, glomerular filtration rate, oxygen saturation, ventilation requirement, intensive care unit admission, and time period, all determined during the first 48 hours. RESULTS: Adjusted logistic regression analyses demonstrated a significant decrease in mortality with prophylactic use of apixaban (odds ratio [OR] 0.46, p = 0.001) and enoxaparin (OR = 0.49, p = 0.001). Therapeutic apixaban was also associated with decreased mortality (OR 0.57, p = 0.006) but was not more beneficial than prophylactic use when analyzed over the entire cohort or within D-dimer stratified categories. Higher D-dimer levels were associated with increased mortality (p < 0.0001). When adjusted for these same comorbidities within D-dimer strata, patients with D-dimer levels < 1 µg/mL did not appear to benefit from anticoagulation while patients with D-dimer levels > 10 µg/mL derived the most benefit. There was no increase in transfusion requirement with any of the anticoagulants used. CONCLUSION: We conclude that COVID-19+ patients with moderate or severe illness benefit from anticoagulation and that apixaban has similar efficacy to enoxaparin in decreasing mortality in this disease.
    背景与目标:
  • 【阿哌沙班与目前房颤患者卒中预防标准的成本-效果.】 复制标题 收藏 收藏
    DOI:10.1093/eurheartj/ehu006 复制DOI
    作者列表:Dorian P,Kongnakorn T,Phatak H,Rublee DA,Kuznik A,Lanitis T,Liu LZ,Iloeje U,Hernandez L,Lip GY
    BACKGROUND & AIMS: AIMS:Warfarin, a vitamin K antagonist (VKA), has been the standard of care for stroke prevention in patients with atrial fibrillation (AF). Aspirin is recommended for low-risk patients and those unsuitable for warfarin. Apixaban is an oral anticoagulant that has demonstrated better efficacy than warfarin and aspirin in the ARISTOTLE and AVERROES studies, respectively, and causes less bleeding than warfarin. We evaluated the potential cost-effectiveness of apixaban against warfarin and aspirin from the perspective of the UK payer perspective. RESULTS AND METHODS:A lifetime Markov model was developed to evaluate the pharmacoeconomic impact of apixaban compared with warfarin and aspirin in VKA suitable and VKA unsuitable patients, respectively. Clinical events considered in the model include ischaemic stroke, haemorrhagic stroke, intracranial haemorrhage, other major bleed, clinically relevant non-major bleed, myocardial infarction, cardiovascular hospitalization and treatment discontinuations; data from the ARISTOTLE and AVERROES trials and published mortality rates and event-related utility rates were used in the model. Apixaban was projected to increase life expectancy and quality-adjusted life years (QALYs) compared with warfarin and aspirin. These gains were expected to be achieved at a drug acquisition-related cost increase over lifetime. The estimated incremental cost-effectiveness ratio was £11 909 and £7196 per QALY gained with apixaban compared with warfarin and aspirin, respectively. Sensitivity analyses indicated that results were robust to a wide range of inputs. CONCLUSIONS:Based on randomized trial data, apixaban is a cost-effective alternative to warfarin and aspirin, in VKA suitable and VKA unsuitable patients with AF, respectively.
    背景与目标:
  • 4 Apixaban: first global approval. 复制标题 收藏 收藏

    【Apixaban: 首次全球批准。】 复制标题 收藏 收藏
    DOI:10.2165/11596820-000000000-00000 复制DOI
    作者列表:Watson J,Whiteside G,Perry C
    BACKGROUND & AIMS: :Apixaban (Eliquis™), an oral direct factor Xa inhibitor, is being developed by Bristol-Myers Squibb and Pfizer as a therapy for the prevention and/or treatment of thrombotic disorders. Apixaban has been approved in the EU for the prevention of venous thromboembolism (VTE) after hip or knee replacement. A rolling submission for approval of apixaban for the prevention of stroke in patients with atrial fibrillation has also been initiated in the US. Worldwide phase III development of apixaban is underway for the prevention and treatment of VTE, and prevention of stroke in patients with atrial fibrillation. Development for acute coronary syndromes has been stopped following the discontinuation of the phase III APPRAISE-II trial. This article summarizes the milestones in the development of apixaban leading to this first approval for the prevention of VTE after hip or knee replacement.
    背景与目标: : 阿哌沙班 (Eliquis™百时美施贵宝 (Bristol-Myers Squibb) 和辉瑞 (Pfizer) 正在开发一种口服直接因子Xa抑制剂,作为预防和/或治疗血栓性疾病的疗法。阿哌沙班已在欧盟被批准用于预防髋关节或膝关节置换术后静脉血栓栓塞 (VTE)。在美国,还开始了批准阿哌沙班用于预防房颤患者中风的滚动提交。阿哌沙班的全球III期开发正在进行中,用于预防和治疗VTE以及预防房颤患者的中风。终止III期评估-II试验后,急性冠状动脉综合征的发展已停止。本文总结了阿哌沙班发展的里程碑,从而首次批准用于预防髋关节或膝关节置换术后的VTE。
  • 【阿哌沙班成功治疗WATCHMAN装置相关血栓: 一例报告。】 复制标题 收藏 收藏
    DOI:10.1097/MD.0000000000008693 复制DOI
    作者列表:Wong CK,Chan PH,Lam CC,Kwok OH,Lam YY,Siu CW
    BACKGROUND & AIMS: RATIONALE:Among atrial fibrillation patients with high risk of bleeding, left atrial appendage occlusion has emerged as an alternative to long-term oral anticoagulation therapy for stroke prevention. Device-related thrombus remains a major concern because it may result in recurrent embolic events. To date, there is no consensus on the optimal method of treating device-related-thrombus. PATIENT CONCERNS:A 78-year-old man with atrial fibrillation had an episode of intracranial hemorrhage while taking warfarin. He subsequently underwent percutaneous placement of a 30-mm Watchman device to the left atrial appendage. He was prescribed dual anti-platelet therapy with aspirin and clopidogrel. DIAGNOSIS:Reassessment echocardiography 3 months later found device-related thrombus. INTERVENTIONS:The antithrombotic regimen was switched from dual antiplatelet therapy to apixaban. OUTCOMES:Reassessment echocardiography 3 months later revealed complete resolution of the device-related thrombus. Apixaban was stopped. He had dual antiplatelet therapy for 6 more months followed by life-long aspirin. There was no bleeding complication since implantation of Watchman device. LESSONS:We demonstrated successful treatment of device-related thrombus with a short course of apixaban with complete resolution of thrombus. Further randomized controlled trials are required to determine the choice and duration of drug therapy for device-related thrombus.
    背景与目标:
  • 【阿哌沙班在预防非瓣膜性心房颤动中中风和全身性栓塞的作用.】 复制标题 收藏 收藏
    DOI:10.1358/dot.2013.49.7.1980498 复制DOI
    作者列表:Pujadas-Mestres L,Escolar G,Arellano-Rodrigo E,Galán AM
    BACKGROUND & AIMS: :Conventional anticoagulant therapies can significantly reduce the risk of stroke and related complications in patients with atrial fibrillation (AF). Classic oral anticoagulants based on vitamin K antagonism have shown effectiveness in the prevention of thromboembolic complications in this clinical setting. Unfortunately, vitamin K antagonists that have shown effectiveness in the prevention of thromboembolic complications in patients with nonvalvular AF hold inherent limitations including delayed onset of action, narrow therapeutic index, variability of their response, need for repeated control and numerous interactions with food and other drugs. Since the frequency of stroke related to AF increases with age, guidelines from different scientific societies advise that the risk of bleeding for a patient should be quantified before exposure to anticoagulation and balanced against the risk of stroke with and without anticoagulation. A consequence of assessing this risk/benefit balance is that not all patients with AF at thromboembolic risk receive adequate anticoagulant treatment. Apixaban is a new oral anticoagulant with a direct, specific and reversible inhibitory action on coagulation factor Xa and with demonstrated safety and efficacy in the prophylaxis and treatment of venous thromboembolism in several clinical studies involving thousands of patients subjected to major orthopedic surgery. Results of two large phase III trials have demonstrated the efficacy and safety of apixaban compared with aspirin or warfarin, in the prevention of stroke in patients with AF. Apixaban demonstrated superiority over classic vitamin K antagonists on the previously specified outcomes of stroke, systemic embolism, major bleeding and death. For those patients unsuitable for treatment with vitamin K antagonists because of an excessive bleeding risk, apixaban showed more efficacy than aspirin in stroke prevention with a not statistically significant modest increase of major bleeding.
    背景与目标: : 常规的抗凝治疗可以显着降低房颤 (AF) 患者的中风和相关并发症的风险。基于维生素k拮抗作用的经典口服抗凝剂已显示出在该临床环境中预防血栓栓塞并发症的有效性。不幸的是,已显示出对非瓣膜性AF患者的血栓栓塞并发症预防有效的维生素k拮抗剂具有固有的局限性,包括作用延迟,治疗指数狭窄,反应变异性,需要重复控制以及与食物和其他药物的多种相互作用。由于与AF相关的卒中频率随着年龄的增长而增加,因此来自不同科学社会的指南建议,在接受抗凝治疗之前,应量化患者的出血风险,并平衡有无抗凝治疗的中风风险。评估这种风险/收益平衡的结果是,并非所有具有血栓栓塞风险的AF患者都接受了足够的抗凝治疗。阿哌沙班是一种新型口服抗凝剂,对凝血因子Xa具有直接,特异性和可逆的抑制作用,并在预防和治疗静脉血栓栓塞症方面具有安全性和有效性,涉及数千例接受骨科手术的患者。两项大型III期试验的结果表明,与阿司匹林或华法林相比,阿哌沙班在预防房颤患者中风方面的有效性和安全性。阿哌沙班在先前指定的中风,全身性栓塞,大出血和死亡的结局方面表现出优于经典的维生素k拮抗剂的优势。对于那些由于出血风险过大而不适合使用维生素k拮抗剂治疗的患者,阿哌沙班在预防中风方面显示出比阿司匹林更高的功效,但主要出血的增加在统计学上没有显着增加。
  • 【阿哌沙班: 一种新兴的口服因子Xa抑制剂。】 复制标题 收藏 收藏
    DOI:10.1007/s11239-009-0421-4 复制DOI
    作者列表:Roser-Jones C,Becker RC
    BACKGROUND & AIMS: :Apixaban, an oral direct factor Xa inhibitor, is currently in late stage clinical development for the prevention and treatment of thromboembolic diseases. In comparison with current treatment standards for venous thromboembolism (VTE) prophylaxis, apixaban has shown decreased rates of clinically significant bleeding with mixed results in terms of non-inferiority for VTE events. Secondary treatment of VTE with apixaban is currently in phase III clinical study after earlier trials showed comparable safety and efficacy outcomes. The APPRAISE-1 trial, a phase II investigation of apixaban versus placebo following acute coronary syndrome showed a higher risk of clinically significant bleeding in addition to a trend toward decreased ischemic events. A large, international phase III clinical study (APPRAISE-2) of apixaban following acute coronary syndrome is currently underway. Large, phase III studies testing apixaban for the prevention of vascular events in subjects with non-valvular atrial fibrillation are also ongoing.
    背景与目标: : 阿哌沙班是一种口服直接因子Xa抑制剂,目前在预防和治疗血栓栓塞性疾病方面处于晚期临床开发阶段。与目前预防静脉血栓栓塞 (VTE) 的治疗标准相比,阿哌沙班的临床显着出血率降低,VTE事件的非劣效性结果参差不齐。在早期试验显示出相当的安全性和有效性结果后,阿哌沙班的VTE二次治疗目前处于III期临床研究中。评估-1试验是急性冠状动脉综合征后阿哌沙班与安慰剂的II期研究,除了缺血性事件减少的趋势外,临床上显着出血的风险更高。目前正在进行急性冠状动脉综合征后阿哌沙班的大型国际III期临床研究 (评估-2)。大型III期研究也在进行中,测试阿哌沙班预防非瓣膜性房颤患者的血管事件。
  • 【阿哌沙班与华法林预防心房颤动消融围手术期脑血栓栓塞的比较: 多中心前瞻性随机研究.】 复制标题 收藏 收藏
    DOI:10.1111/jce.12928 复制DOI
    作者列表:Kuwahara T,Abe M,Yamaki M,Fujieda H,Abe Y,Hashimoto K,Ishiba M,Sakai H,Hishikari K,Takigawa M,Okubo K,Takagi K,Tanaka Y,Nakajima J,Takahashi A
    BACKGROUND & AIMS: INTRODUCTION:Stroke can be a life-threatening complication of atrial fibrillation (AF) catheter ablation. Uninterrupted warfarin treatment contributes to minimizing the risk of stroke complications. METHODS AND RESULTS:This was a prospective, open-label, randomized, multicenter study assessing the safety and efficacy of apixaban for the prevention of cerebral thromboembolism complicating AF catheter ablation. Two hundred patients with drug-resistant AF were equally assigned to take either apixaban (5 mg or 2.5 mg twice daily) or warfarin (target international normalized ratio, 2-3) for at least 1 month before AF ablation. Neither drug regimen was interrupted throughout the operative period. Diffusion-weighted magnetic resonance imaging was performed for all patients to detect silent cerebral infarction (SCI) after the ablation. Primary outcomes were defined as the occurrence of stroke, transient ischemic attack, SCI, or major bleeding that required intervention. The secondary outcome was minor bleeding. The groups did not statistically differ in patients' backgrounds or procedural parameters. During AF ablation, the apixaban group required administration of more heparin to maintain an activated clotting time > 300 seconds than the warfarin group (apixaban, 14,000 ± 4,000 units; warfarin, 9,000 ± 3,000 units). Three primary outcome events occurred in each group (apixaban, 2 SCI and 1 major bleed; warfarin, 3 SCI, P = 1.00), and 3 and 4 secondary outcome events occurred in the apixaban and warfarin groups (P = 0.70), respectively. CONCLUSION:Apixaban has similar safety and effectiveness to warfarin for the prevention of cerebral thromboembolism during the periprocedural period of AF ablation.
    背景与目标:
  • 【在日本非瓣膜性房颤患者中,阿哌沙班,达比加群和小剂量利伐沙班与华法林的出血风险比较: 对行政索赔数据的倾向匹配分析。】 复制标题 收藏 收藏
    DOI:10.1080/03007995.2017.1374935 复制DOI
    作者列表:Kohsaka S,Murata T,Izumi N,Katada J,Wang F,Terayama Y
    BACKGROUND & AIMS: OBJECTIVES:There is scarce evidence comparing novel oral anticoagulants (NOACs) with warfarin in real-world settings in Japan. This study compared the risk of bleeding events among patients with non-valvular atrial fibrillation (NVAF) initiating treatment with NOACs versus warfarin. METHODS:A retrospective cohort study was conducted using a de-identified electronic health record based database of health claims and Diagnosis Procedure Combination data from 275 consenting hospitals in Japan. NVAF patients newly initiated on oral anticoagulants were eligible. Based on the first prescription, patients were assigned to 5/2.5 mg BID apixaban, 150/110 mg BID dabigatran, 15/10 mg QD rivaroxaban (approved dose lower in Japan compared to Western countries [20/15 mg QD]) or warfarin groups. One-to-one propensity score matching (PSM) was used to balance patient characteristics between warfarin and each NOAC. Patients were followed up to 1 year post-first prescription. RESULTS:Among 38,662 eligible patients, a total of 5977, 5090, and 6726 matched pairs were identified for warfarin versus apixaban, warfarin versus dabigatran, and warfarin versus rivaroxaban, respectively after PSM. Compared to warfarin, apixaban (hazard ratio [HR] 0.586; 95% CI 0.421-0.815), dabigatran (HR 0.617; 0.425-0.895) and rivaroxaban (HR 0.693; 0.514-0.933) were associated with a significantly lower risk of major bleeding. The risk of any bleeding was significantly lower for apixaban (HR 0.782; 0.682-0.896), but not for dabigatran (HR 0.988; 0.860-1.135) or rivaroxaban (HR 0.938; 0.832-1.057) when comparing to warfarin. CONCLUSIONS:Among Japanese patients with NVAF, treatment with apixaban 5/2.5 mg BID was associated with a significantly lower risk of major bleeding and any bleeding when compared to warfarin. Treatment with dabigatran 150/110 mg BID or rivaroxaban 15/10 mg QD was associated with a significantly lower risk of major bleeding, but not any bleeding, than warfarin. The potential benefit of individual NOACs in real-world practice needs to be assessed further.
    背景与目标:
  • 【四因素凝血酶原复合物浓缩物在健康受试者中逆转阿哌沙班抗凝作用: 一项随机三期交叉研究。】 复制标题 收藏 收藏
    DOI:10.1111/jth.13815 复制DOI
    作者列表:Song Y,Wang Z,Perlstein I,Wang J,LaCreta F,Frost RJA,Frost C
    BACKGROUND & AIMS: :Essentials Prothrombin complex concentrates (PCCs) may reverse the effect of factor Xa (FXa) inhibitors. We conducted an open-label, randomized, placebo-controlled, three-period crossover study in 15 subjects. Both PCCs rapidly reversed apixaban-mediated decreases in mean endogenous thrombin potential. Four-factor PCC administration had no effect on apixaban pharmacokinetics or anti-FXa activity. SUMMARY:Background Currently, there is no approved reversal agent for direct activated factor Xa (FXa) inhibitors; however, several agents are under investigation, including prothrombin complex concentrates (PCCs). Objective This open-label, randomized, placebo-controlled, three-period crossover study assessed the effect of two four-factor PCCs on apixaban pharmacodynamics and pharmacokinetics in 15 healthy subjects. Methods Subjects received apixaban 10 mg twice daily for 3 days. On day 4, 3 h after apixaban, subjects received a 30-min infusion of 50 IU kg-1 Cofact, Beriplex P/N (Beriplex), or saline. Change in endogenous thrombin potential (ETP), measured with a thrombin generation assay (TGA), was the primary endpoint. Secondary endpoints included changes in other TGA parameters, prothrombin time (PT), International Normalized Ratio (INR), activated partial thromboplastin time, anti-FXa activity, apixaban pharmacokinetics, and safety. Results Apixaban-related changes in ETP and several other pharmacodynamic measures occurred following apixaban administration. Both PCCs reversed apixaban's effect on ETP; the differences in adjusted mean change from pre-PCC baseline to end of infusion were 425 nm min (95% confidence interval [CI] 219.8-630.7 nm min; P < 0.001) for Cofact, and 91 nm min (95% CI - 31.3 to 212.4 nm min; P > 0.05) for Beriplex. Both PCCs returned ETP to pre-apixaban baseline levels 4 h after PCC infusion, versus 45 h for placebo. For both PCCs, mean ETP peaked 21 h after PCC initiation, and then slowly decreased over the following 48 h. Both PCCs reversed apixaban's effect on TGA peak height, PT, and INR. Apixaban pharmacokinetic and anti-FXa profiles were consistent across treatments. Conclusions Cofact and Beriplex reversed apixaban's steady-state effects on several coagulation assessments.
    背景与目标:
  • 【在 “现实世界” 临床实践中,阿哌沙班与华法林在非瓣膜性房颤患者中的有效性和安全性。76,940名患者的倾向匹配分析。】 复制标题 收藏 收藏
    DOI:10.1160/TH17-01-0068 复制DOI
    作者列表:Li XS,Deitelzweig S,Keshishian A,Hamilton M,Horblyuk R,Gupta K,Luo X,Mardekian J,Friend K,Nadkarni A,Pan X,Lip GYH
    BACKGROUND & AIMS: :The ARISTOTLE trial showed a risk reduction of stroke/systemic embolism (SE) and major bleeding in non-valvular atrial fibrillation (NVAF) patients treated with apixaban compared to warfarin. This retrospective study used four large US claims databases (MarketScan, PharMetrics, Optum, and Humana) of NVAF patients newly initiating apixaban or warfarin from January 1, 2013 to September 30, 2015. After 1:1 warfarin-apixaban propensity score matching (PSM) within each database, the resulting patient records were pooled. Kaplan-Meier curves and Cox proportional hazards models were used to estimate the cumulative incidence and hazard ratios (HRs) of stroke/SE and major bleeding (identified using the first listed diagnosis of inpatient claims) within one year of therapy initiation. The study included a total of 76,940 (38,470 warfarin and 38,470 apixaban) patients. Among the 38,470 matched pairs, 14,563 were from MarketScan, 7,683 were from PharMetrics, 7,894 were from Optum, and 8,330 were from Humana. Baseline characteristics were balanced between the two cohorts with a mean (standard deviation [SD]) age of 71 (12) years and a mean (SD) CHA2DS2-VASc score of 3.2 (1.7). Apixaban initiators had a significantly lower risk of stroke/SE (HR: 0.67, 95 % CI: 0.59-0.76) and major bleeding (HR: 0.60, 95 % CI: 0.54-0.65) than warfarin initiators. Different types of stroke/SE and major bleeding - including ischaemic stroke, haemorrhagic stroke, SE, intracranial haemorrhage, gastrointestinal bleeding, and other major bleeding - were all significantly lower for apixaban compared to warfarin treatment. Subgroup analyses (apixaban dosage, age strata, CHA2DS2-VASc or HAS-BLED score strata, or dataset source) all show consistently lower risks of stroke/SE and major bleeding associated with apixaban as compared to warfarin treatment. This is the largest "real-world" study on apixaban effectiveness and safety to date, showing that apixaban initiation was associated with significant risk reductions in stroke/SE and major bleeding compared to warfarin initiation after PSM. These benefits were consistent across various high-risk subgroups and both the standard- and low-dose apixaban dose regimens.
    背景与目标: : ARISTOTLE试验显示,与华法林相比,使用阿哌沙班治疗的非瓣膜性房颤 (NVAF) 患者中风/全身性栓塞 (SE) 和大出血的风险降低。这项回顾性研究使用了四个美国大型索赔数据库 (MarketScan,PharMetrics,Optum和Humana),这些NVAF患者从2013年1月1日到2015年9月30日新开始使用阿哌沙班或华法林。在每个数据库中进行1:1华法林-阿哌沙班倾向评分匹配 (PSM) 后,汇总所得患者记录。使用Kaplan-Meier曲线和Cox比例风险模型来估计治疗开始一年内中风/SE和大出血 (使用首次列出的住院患者索赔诊断确定) 的累积发生率和风险比 (HRs)。该研究共纳入76,940名患者 (38,470华法林和38,470阿哌沙班)。在38,470配对中,14,563来自marketsccan,7,683来自PharMetrics,7,894来自Optum,8,330来自Humana。基线特征在两个队列之间是平衡的,平均 (标准差 [SD]) 年龄为71 (12) 岁,平均 (SD) CHA2DS2-VASc得分为3.2 (1.7)。与华法林引发剂相比,阿哌沙班引发剂的卒中/SE (HR: 0.67,95   % CI: 0.59-0.76) 和大出血 (HR: 0.60,95   % CI: 0.54-0.65) 风险显著降低。与华法林治疗相比,阿哌沙班的不同类型的中风/SE和主要出血 (包括缺血性中风,出血性中风,SE,颅内出血,胃肠道出血和其他主要出血) 均显着降低。亚组分析 (阿哌沙班剂量,年龄层,CHA2DS2-VASc或HAS-BLED评分层或数据集来源) 均显示与华法林治疗相比,与阿哌沙班相关的卒中/硒和大出血的风险始终较低。这是迄今为止关于阿哌沙班有效性和安全性的最大 “现实世界” 研究,表明与PSM后的华法林相比,阿哌沙班的启动与中风/SE和大出血的显着风险降低相关。这些获益在各种高危亚组以及标准和低剂量阿哌沙班剂量方案中是一致的.
  • 【阿哌沙班双重或三重抗血栓治疗对体内和体外灌注室模型中血栓形成的影响: 开放标签,对照,顺序研究。】 复制标题 收藏 收藏
    DOI:10.1097/MD.0000000000004145 复制DOI
    作者列表:Weisshaar S,Litschauer B,Bucher S,Riesenhuber M,Kapiotis S,Kyrle PA,Wolzt M
    BACKGROUND & AIMS: BACKGROUND:There is a need to optimize pharmacological treatment in patients with acute coronary syndrome and concomitant atrial fibrillation, in particular with newer antithrombotic medicines. We have therefore studied if dual or triple combination of antithrombotic agents exert similar effects on coagulation activation in an in vivo model in the skin microvasculature and in an ex vivo perfusion chamber. METHODS AND RESULTS:Shed blood platelet activation (β-thromboglobulin [β-TG]), thrombin generation (thrombin-antithrombin complex [TAT]) and volume as well as markers of thrombus size (D-dimer) and its platelet content (P-selectin) in a perfusion chamber were studied in a sequential, open-label, parallel group trial in 40 healthy male volunteers (n = 20 per group). Subjects received ticagrelor and apixaban without or with acetylsalicylic acid (ASA). Outcome parameters were assessed at 3 hours after therapy dosing, and at steady-state trough and peak conditions.A triple or dual therapy induced a comparable decrease in shed blood β-TG at 3 hours after therapy dosing but was more pronounced at steady-state conditions with the more intense treatment combination. During both antithrombotic regimens a similarly sustained inhibition in thrombin generation was observed which was accompanied by comparable increases in shed blood volume. In contrast, no treatment effect could be observed in the perfusion chamber experiment. CONCLUSION:Ticagrelor and apixaban with or without ASA inhibit platelet activation and thrombin formation in vivo in healthy subjects. Platelet inhibition was greater at steady-state conditions after triple therapy administration.
    背景与目标:
  • 【在德国常规实践中,阿哌沙班和维生素k拮抗剂治疗非瓣膜性房颤患者的比较有效性和安全性。】 复制标题 收藏 收藏
    DOI:10.1016/j.hlc.2017.04.002 复制DOI
    作者列表:Coleman CI,Peacock WF,Antz M
    BACKGROUND & AIMS: BACKGROUND:Scarce data comparing real-world outcomes between apixaban and vitamin K antagonist (VKA) users with nonvalvular atrial fibrillation (NVAF) are available. We sought to assess the effectiveness and safety of newly-initiated apixaban vs. VKA in German NVAF patients. MATERIALS AND METHODS:We performed a retrospective analysis in German outpatients using IMS Disease Analyzer data. Adults newly-initiated on apixaban or a VKA from January 2013 to March 2015 with a diagnosis of NVAF on the day of the first qualifying oral anticoagulant (OAC) prescription (index date) or any time during 1 year prior, and at least 1 year of follow-up were included. Patients experiencing a prior event in the composite endpoint, receiving an OAC before the index date, >1 OAC on the index date or switched to another OAC during follow-up were excluded. Apixaban and VKA users were 1:1 propensity-score matched. We evaluated the composite of ischaemic stroke, transient ischaemic attack (TIA), myocardial infarction (MI) or intracranial haemorrhage (ICH) in the year after OAC initiation. Cox regression was used to calculate hazard ratios (HRs) and 95% confidence intervals (CIs). RESULTS:In total, 835 apixaban and 835 VKA users were matched. Forty-one composite events were identified. Hazard of the composite endpoint did not differ between apixaban and VKA users (HR=0.87, 95%CI=0.47-1.60). Ischaemic stroke and MI occurred at dissimilar (albeit not statistically significant) rates between apixaban and VKA therapy (HR=1.51, 95%CI=0.54-4.24) and (HR=0.33, 95%CI=0.11-1.03). Only two patients (both in the apixaban cohort) experienced an ICH. CONCLUSIONS:Apixaban and VKA therapy were associated with a similar impact on the composite endpoint in real-world German practice. Additional investigation is needed to evaluate the numeric trends of ischaemic stroke and decreased number of MIs observed with apixaban, as well as the high rate of reduced dose apixaban use found in this analysis.
    背景与目标:
  • 14 Assembling the Puzzle of Apixaban Solid Forms. 复制标题 收藏 收藏

    【组装阿哌沙班固体形式的拼图。】 复制标题 收藏 收藏
    DOI:10.1021/acs.molpharmaceut.8b00060 复制DOI
    作者列表:Barbas R,Puigjaner C,Prohens R
    BACKGROUND & AIMS: :An in-depth analysis of the solid forms of the anticoagulant drug Apixaban (APX) has been conducted to sort out the confusion in the scientific and patent literature regarding the solid forms landscape. The nomenclature employed and the accompanying characterization data are often unclear and incomplete, leading to a situation in which apparently the same form has been reported by different authors or claimed by different inventors. A comprehensive solid forms screen and a full and careful comparison with the literature data has been performed to draw a reliable picture of the solid forms landscape of APX.
    背景与目标: : 已经对抗凝药物阿哌沙班 (APX) 的固体形式进行了深入分析,以理清科学和专利文献中有关固体形式景观的困惑。所采用的命名法和随附的表征数据通常不清楚且不完整,从而导致一种情况,即不同的作者已经报告了相同的形式,或者不同的发明人声称了相同的形式。已进行了全面的实体形式屏幕,并与文献数据进行了全面而仔细的比较,以绘制出APX实体形式的可靠图片。
  • 【法国房颤患者的中风预防: 新型口服抗凝剂 (阿哌沙班,达比加群和利伐沙班),华法林和阿司匹林的比较成本效益。】 复制标题 收藏 收藏
    DOI:10.3111/13696998.2014.923891 复制DOI
    作者列表:Lanitis T,Cotté FE,Gaudin AF,Kachaner I,Kongnakorn T,Durand-Zaleski I
    BACKGROUND & AIMS: OBJECTIVES:To conduct an economic evaluation of the currently prescribed treatments for stroke prevention in patients with non-valvular atrial fibrillation (NVAF) including warfarin, aspirin, and novel oral anticoagulants (NOACs) from a French payer perspective. METHODS:A previously published Markov model was adapted in accordance to the new French guidelines of the Commission for Economic Evaluation and Public Health (CEESP), to adopt the recommended efficiency frontier approach. A cohort of patients with NVAF eligible for stroke preventive treatment was simulated over lifetime. Clinical events modeled included strokes, systemic embolism, intracranial hemorrhage, other major bleeds, clinically relevant non-major bleeds, and myocardial infarction. Efficacy and bleeding data for warfarin, apixaban, and aspirin were obtained from ARISTOTLE and AVERROES trials, whilst efficacy data for other NOACs were from published indirect comparisons. Acute medical costs were obtained from a dedicated analysis of the French national hospitalization database (PMSI). Long-term medical costs and utility data were derived from the literature. Univariate and probabilistic sensitivity analyses were performed to assess the robustness of the model projections. RESULTS:Warfarin and apixaban were the two optimal treatment choices, as the other five treatment strategies including aspirin, dabigatran 110 mg, dabigatran in sequential dosages, dabigatran 150 mg, and rivaroxaban were strictly dominated on the efficiency frontier. Further, apixaban was a cost-effective alternative vs warfarin with an incremental cost of €2314 and an incremental quality-adjusted life year (QALY) of 0.189, corresponding to an incremental cost-effectiveness ratio (ICER) of €12,227/QALY. CONCLUSIONS:Apixaban may be the most economically efficient alternative to warfarin in NVAF patients eligible for stroke prevention in France. All other strategies were dominated, yielding apixaban as a less costly yet more effective treatment alternative. As formally requested by the CEESP, these results need to be verified in a French clinical setting using stroke reduction and bleeding safety observed in real-life patient cohorts using these anticoagulants.
    背景与目标:

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