阿哌沙班预防心房颤动患者的卒中

阿哌沙班是激活Ⅹ因子(Ⅹa)抑制剂,具有快速吸收、线性药代动力学、较少药物相互作用的特点。在不适合接受华法林治疗的心房颤动人群中所进行的随机对照试验证实,阿哌沙班在减少卒中和系统栓塞方面的疗效优于阿司匹林,安全性相似;在至少有1个危险因素的心房颤动人群中进行的与华法林的对照试验中,阿哌沙班可减少卒中和栓塞事件,主要是减少出血性卒中,同时减少重要出血和全因死亡。     

Novel anticoagulants – an update on the latest developments and management for clinicians treating patients on these drugs

There are several novel anticoagulant agents that are being increasingly used as an alternative to warfarin, with these drugs being reported to be at least as effective if not better. Their increased use means that oral care clinicians should have a sound understanding of the mechanism of action, pharmacology, reversal strategies and management of bleeding in patients taking these drugs. Surprisingly, there is little published in the current literature specific to professionals involved in oral health care. In this review, we provide an overview of these drugs and discuss the management of patients who need an oral procedure based on currently available literature and clinical trials.     

阿哌沙班中3个杂质的合成研究

目的设计并合成阿哌沙班中的3个杂质。方法以2-氯-2-[2-(4-甲氧基苯基)亚肼基]乙酸乙酯和5,6-二氢-3-(4-吗啉基)-1-[4-(2-氧代-1-哌啶基)苯基]-2(1H)-吡啶酮为起始原料,经过环合和水解反应得到目标化合物1,化合物1分别经过水解和取代反应得到目标化合物2和3。结果合成了目标化合物,并利用MS、~1H-NMR和~(13)C-NMR确证了结构:目标化合物1~3的质量分数分别为99.3%、99.1%、99.2%。结论 3个杂质的合成和纯化为阿哌沙班的杂质研究奠定了物质基础。     

口服直接Ⅹa因子抑制剂致血管炎的文献分析

目的： 探讨口服直接Ⅹa因子抑制剂致血管炎的临床特点及可能机制,为临床用药提供参考。方法： 检索国内外文献数据库PubMed、SCI、Embase（OVIP）、中国知网、万方数据库、维普数据库中关于口服直接Ⅹa因子致血管炎的文献报道,检索时间均自建库到2019年12月,筛选文献后提取文献信息,包括患者基本信息、用药情况、药品不良反应发生、处理和转归等信息,并进行分析。结果： 共纳入7份报告,7例患者,6例涉及利伐沙班,1例涉及阿哌沙班,其中男4例,女3例,平均年龄（56.43±19.89）岁,不良反应血管炎类型均经活检证实为白细胞破裂性血管炎,发生时间距首次用药最短4 d,最长3个月,其ADR关联性评价为很可能（5/7）和高度可能（2/7）,均为严重的ADR,4例停药后好转,3例停药并接受糖皮质激素治疗后好转。结论： 需要重视口服直接Ⅹa因子抑制剂致血管炎的可能,尤其是白细胞破裂性血管炎,促进安全合理用药。     

Comparison of effectiveness and safety of treatment with apixaban vs. other oral anticoagulants among elderly nonvalvular atrial fibrillation patients

Objective: To compare the risk of stroke/systemic embolism (S/SE) and major bleeding (MB) of elderly (≥65 years of age) nonvalvular atrial fibrillation (NVAF) patients initiating apixaban vs. rivaroxaban, dabigatran, or warfarin.

Methods: NVAF patients with Medicare Advantage coverage in the US initiating oral anticoagulants (OACs, index event) were identified from the Humana database (1 January 2013–30 September 2015) and grouped into cohorts depending on OAC initiated. Propensity score matching (PSM), 1:1, was conducted among patients treated with apixaban vs. each other OAC, separately. Rates of S/SE and MB were evaluated in the follow-up. Cox regressions were used to compare the risk of S/SE and MB between apixaban and each of the other OACs during the follow-up.

Results: The matched pairs of apixaban vs. rivaroxaban (n?=?13,620), apixaban vs. dabigatran (n?=?4654), and apixaban vs. warfarin (n?=?14,214) were well balanced for key patient characteristics. Adjusted risks for S/SE (hazard ratio [HR] vs. rivaroxaban: 0.72, p?=?.003; vs. warfarin: 0.65, p?p?p?apixaban vs. rivaroxaban and warfarin. Adjusted risks for S/SE (HR: 0.78, p?=?.27) and MB (HR: 0.82, p?=?.23) of NVAF patients treated with apixaban vs. dabigatran trended to be lower, but did not reach statistical significance.

Conclusions: In the real-world setting after controlling for differences in patient characteristics, apixaban is associated with significantly lower risk of S/SE and MB than rivaroxaban and warfarin, and a trend towards better outcomes vs. dabigatran among elderly NVAF patients in the US.     

新型口服抗凝药在急性缺血性脑卒中的应用

阐述分析新型口服抗凝药在非瓣膜病性心房颤动急性缺血性脑卒中的应用进展。结合华法林制剂使用的局限性、患者服用依从性差、需要反复检测凝血功能繁琐性,就有关新型抗凝药达比加群、利伐沙班、阿哌沙班、依度沙班的药理作用、使用方法及适应证、禁忌证予以阐述。并查阅文献,阐述新型口服抗凝药在非瓣膜病心房颤动性急性缺血性脑卒中的应用特点,对比分析各种药物的代谢规律,探讨其毒副作用,指出相关药物过量使用的拮抗方法,分析存在的不足,提出目前需要亟待解决的问题,以便更好的在临床推广应用,最大限度降低不良反应。