New-generation oral anticoagulants for the prevention of stroke: Implications for neurosurgery

A new generation of oral anticoagulants, namely direct thrombin inhibitors and factor X_a inhibitors, have recently been approved for clinical use in patients with atrial fibrillation. These novel families of drugs have been shown to have favorable efficacy and safety profiles in multiple clinical settings, particularly in the prevention of atrial fibrillation-related stroke, and are likely to become part of everyday practice, making a crossover to neurosurgical patients inevitable. Concern has risen regarding the complexity of managing intracranial and intraspinal hemorrhages related to these drugs. This review aims to provide an update on the most recent advances in oral anticoagulant drug therapy from a neurosurgeon’s perspective. We discuss current evidence for the use of these novel agents, their limitations, existing methods of drug-level monitoring, and controversies related to anticoagulation reversal. We also discuss specific topics such as anticoagulation resumption after intracranial or intraspinal bleeding, perioperative anticoagulant administration, and the possibility of combination with tissue plasminogen activator in the setting of acute ischemic stroke. A special focus is given to the incidence of intracranial and intraspinal hemorrhage associated with each drug.     

达比加群酯与低分子肝素预防髋关节置换术后下肢深静脉血栓的作用比较

目的 比较达比加群酯与低分子肝素预防髋关节置换术后并发下肢深静脉血栓（DVT）的疗效与安全性的差异。方法 选择2014年1月至2015年10月在宣城中心医院住院的单髋或双髋关节置换术患者73例,随机分为基础治疗组（对照组）24例,达比加群酯组（DE组）25例,低分子肝素组（LMWH组）24例。置换后行双下肢彩色多普勒检查评估DVT形成情况,并观察比较各组患者治疗前后血小板计数,凝血酶元时间（PT）变化情况及安全性。结果 DE组和LMWH预防DVT效果优于对照组（P<0.05）,而DE组和LMWH组患者在预防DVT发生上差异无统计学意义（P>0.05）。DE组和LMWH组在治疗期间均无严重出血。结论 达比加群酯与低分子肝素均具有较好的预防髋关节置换后DVT的发生,达比加群酯疗效及安全性与低分子肝素作用相当。     

Dabigatran,rivaroxaban, and apixaban are superior to warfarin in Asian patients with non-valvular atrial fibrillation: An updated meta-analysis

BACKGROUNDMost of the randomized clinical trials that led to the wide use of non-vitamin K antagonist oral anticoagulants for stroke prevention in patients with atrial fibrillation (AF) originated from western countries. AIMTo systematically review and quantitatively synthesize the real-world data regarding the efficacy and safety of dabigatran, rivaroxaban, and apixaban compared to warfarin for stroke prevention in Asian patients with non-valvular AF.METHODSMedline, Cochrane, and ClinicalTrial.gov databases were reviewed. A random-effect model meta-analysis was used and I-square was utilized to assess the heterogeneity. The primary outcome was ischemic stroke. The secondary outcomes were all-cause mortality, major bleeding, intracranial hemorrhage, and gastrointestinal bleeding.RESULTSTwelve studies from East Asia or Southeast Asia and 441450 patients were included. Dabigatran, rivaroxaban, and apixaban were associated with a significant reduction in the incidence of ischemic stroke [hazard ratio (HR) = 0.78, 95% confidence interval (CI): 0.65-0.94; HR = 0.79, 95%CI: 0.74-0.85, HR = 0.70, 95%CI: 0.62-0.78; respectively], all-cause mortality (HR = 0.68, 95%CI: 0.56-0.83; HR = 0.66, 95%CI: 0.52-0.84; HR = 0.66, 95%CI: 0.49-0.90; respectively), and major bleeding (HR = 0.61, 95%CI: 0.54-0.69; HR = 0.70, 95%CI: 0.54-0.90; HR = 0.58, 95%CI: 0.43-0.78; respectively) compared to warfarin.CONCLUSIONDabigatran, rivaroxaban, and apixaban appear to be superior to warfarin in both efficacy and safety in Asians with non-valvular AF.     

达比加群酯不良反应文献的分析

通过检索PubMed、中国知网数据库和维普数据库关于达比加群酯不良反应的文献并对其进行回顾性分析和总结。达比加群酯致ADR的个案报道共73例;其性别分布男性44例（60.3%）,女性29例（39.7%）;年龄分布以70岁以上较多（59例,80.8%）;多发生在用药后6个月内（60例,82.2%）;达比加群酯致ADR临床表现以消化系统损害（50.7%）、血液系统损害（15.1%）和心血管系统损害（11.0%）多见。临床使用达比加群酯过程中应重点考量患者肾功能、年龄、体重和性别等危险因素,并重点监测和防治其ADR,避免ADR的发生。     

Management of venous thromboembolism in cancer patients and the role of the new oral anticoagulants

Patients with cancer are at high risk for venous thromboembolism (VTE). Most clinical guidelines agree that low-molecular-weight heparins (LMWHs) are the preferred anticoagulants for the prevention and treatment of VTE in cancer patients. However, LMWHs require daily injections, weight-adjustment of dose, and can be associated with heparin-induced thrombocytopenia; all of which are important considerations in managing cancer-associated VTE. Comparatively, the new oral anticoagulants offer a more attractive option because of their oral administration, fixed-dose, and lack of routine laboratory monitoring. The results of phase III trials support the efficacy and safety of the new oral anticoagulants in the management of VTE. However, generalizing these findings to cancer patients with VTE is difficult since very few cancer patients were included. In this comprehensive review, we provide an overview of the current treatment of VTE, explore anticoagulant thromboprophylaxis in ambulatory cancer patients, and summarize existing evidence on the efficacy and safety of the new oral anticoagulants for the management of VTE in both non-cancer and cancer populations.