高效液相色谱法检测甲磺酸达比加群酯及有关物质

为了研究甲磺酸达比加群酯的有关物质,本研究合成了7个有关化合物,建立了相关的HPLC检测方法(以XBridge C₁₈为色谱柱,甲醇-0.01 mol/L磷酸二氢钾为流动相梯度洗脱,检测波长为310 nm),并对样品的溶解溶剂和进样体积进行了筛选。结果显示,所建立的HPLC分析方法能使达比加群酯和7个化合物达到完全分离,且重复性好,准确度高,适用于甲磺酸达比加群酯有关物质的检测。     

Dabigatran and rivaroxaban for prevention of venous thromboembolism--systematic review and adjusted indirect comparison

What is known and objective: Dabigatran and rivaroxaban are new oral anticoagulants for thromboprophylaxis after elective orthopaedic surgery. We aimed to systematically compare their relative benefits and harms through meta‐analysis, and adjusted indirect comparison. Methods: We searched PubMed, EMBASE, trial registries and regulatory documents through May 2009 for randomized controlled trials (RCTs) of dabigatran (150 and 220 mg daily) and rivaroxaban (10 mg daily) compared with enoxaparin (40–60 mg daily) in elective orthopaedic surgery. We used random effects meta‐analysis to calculate pooled relative risks (RRs) and 95% confidence intervals (95% CI) for the outcomes of total venous thromboembolism, VTE (deep venous thrombosis, non‐fatal pulmonary embolism and all‐cause mortality), and haemorrhagic adverse events (major and clinically relevant non‐major bleeds). Adjusted indirect comparison was used for the pooled RRs of dabigatran and rivaroxaban with enoxaparin as the common control. Results: Rivaroxaban was superior to enoxaparin for the prevention of venous thromoboembolism (RR 0·56, 95% CI 0·43–0·73, P < 0·0001), with a trend for increased haemorrhage (RR 1·26, 95% CI 0·94–1·69, P = 0·13). Dabigatran was not superior to enoxaparin for prevention of VTE (RR 1·12, 95% 0·97–1·29, P = 0·12), and did not reduce haemorrhage risk (RR 1·10, 95% 0·90–1·35, P = 0·32). Adjusted indirect comparison showed that rivaroxaban was superior to dabigatran in preventing VTE, RR 0·50 (95% CI 0·37–0·68), but with a slight trend towards increased haemorrhage RR 1·14 (95% CI 0·80–1·64). What is new and conclusion: Rivaroxaban may be more effective than dabigatran for prevention of VTE after elective orthopaedic surgery but might also slightly increase the risk of haemorrhage.     

Idarucizumab for dabigatran reversal: the first 6 months in a tertiary centre

This retrospective audit reviews patients on dabigatran presenting with bleeding or requiring urgent surgery in the Wellington region, whether they received idarucizumab appropriately and the outcome of episodes. Eighty patients were identified with bleeding or need for urgent surgery, 14 of which received idarucizumab. In patients who received idarucizumab, use was safe, effective and overall appropriate. Idarucizumab was underutilised with patients who could have benefited not receiving it; however, some patients who were treated may not have required it. Increased awareness and use may improve outcomes.     

新型口服抗凝药达比加群酯研究进展

达比加群酯是一种新型合成的直接凝血酶抑制剂,口服经胃肠吸收后,在体内转化为具有直接抗凝血活性的达比加群。现主要对达比加群酯的药理学、相关临床研究、临床应用前景进行综述。     

房颤危险分层及抗凝治疗研究进展

房颤(AF)是临床常见的心律失常,脑卒中是其主要并发症。临床治疗的重要环节是栓塞预防,而AF患者的栓塞危险分层有助于临床个体化治疗。本文分析权威指南的AF栓塞危险分层标准,综述达比加群酯、利伐沙班和阿哌沙班等新型抗凝药的临床应用研究进展。     

达比加群酯药物利用评价标准的建立与回顾性分析

目的:建立达比加群酯药物利用评价标准(drug use evaluation, DUE),为临床合理应用达比加群酯提供参考。方法:以达比加群酯药品说明书为基础,参考相关指南和文献,通过专家咨询法制订达比加群酯药物利用评价标准,并采用回顾性研究方法,对湖北省某大型三甲医院2021年1-6月使用达比加群酯的住院患者用药进行合理性评价,具体包括适应证、用法用量、联合用药、禁忌证、不良反应监测及药物转换等。结果:共纳入501份病例,完全符合评价标准的合理率为91.42%,不合理应用常见于适应证不适宜(2.2%)和用法用量不适宜(2.0%),同时存在30.3%的联合用药的高风险。结论:建立的达比加群酯的DUE具有较强的科学性、实用性和可行性,该院达比加群酯临床应用中尚存在一些问题,应进一步加强干预,促进临床合理用药。     

住院患者达比加群酯的临床应用调查与分析

目的:调查并分析苏州大学附属第一医院(以下称“我院”)达比加群酯的使用现状,为规范其临床应用提供依据。方法:汇总国内外达比加群酯的相关指南和专家共识及建议并结合药品说明书形成其临床应用合理性评价标准(以下简称“标准”),同时回顾性收集2020年度入住我院并使用达比加群酯的患者资料,对其适应证、禁忌证、用法用量、药物相互作用、桥接转换及围手术期使用等情况进行统计分析。结果:共检索到文献978篇,最终纳入11篇形成“标准”。213例使用达比加群的患者中有56例(26.29%)存在用药不合理现象,其中无适应证用药3例(1.41%),禁忌证用药1例(0.47%),用法用量不合理19例(8.92%),桥接转换不合理4例(1.88%),存在不良药物相互作用1例(1.08%),围手术期用药不合理28例(13.15%)。结论:我院住院患者达比加群酯的临床应用与“标准”仍存在一定差距,且不同科室间存在明显的差异,尤以给药频次和围手术期用药不合理最为突出。药师应及时关注达比加群酯及血栓栓塞性疾病相关循证医学证据的更新,同时积极参与全院患者的抗凝药物管理,进一步规范达比加群酯的临床应用。     

达比加群酯治疗老年非瓣膜性心房颤动的有效性和安全性评价

目的 探讨达比加群酯治疗老年非瓣膜性心房颤动的有效性和安全性，为临床治疗和合理用药提供参考。方法 采用自身对照的研究方法，收集2020年12月-2021年6月在上海市第七人民医院住院或门诊的老年非瓣膜性房颤患者80例，年龄65~80岁。给予口服达比加群酯胶囊110 mg/次，每天2次（早、晚各1次），治疗6个月。随访，观察服药1个月、6个月后患者的凝血功能指标，包括活化部分凝血活酶时间(APTT)、血浆凝血酶时间(TT)、纤维蛋白原(FIB)和D-二聚体(D-D)；肝功能指标，包括丙氨酸氨基转移酶(ALT)、谷草转氨酶(AST)和总胆红素(TBIL)，肾功能指标，包括尿素(UREA)和肾小球滤过率估计值(eGFR)；血常规指标，包括血红蛋白量(HGB)和红细胞沉降率(ESR)。结果 患者服用达比加群酯治疗1个月、6个月后与服药前比较：APTT、TT均有升高，差异有统计学意义（P<0.05）；肝功能指标、肾功能指标、血常规指标差异无统计学意义（P>0.05）；共发生25例不良事件，不良事件发生率为31.25%，并未发生严重出血和威胁生命或器官衰竭的出血。结论 达比加群酯在治疗老年非瓣膜性心房颤动方面，有较好的疗效和安全性。