Kwok Lisa, Molckovsky Dana, Boucher Michel
Fairview Family Health Network, 1333 Sheppard Avenue East, Toronto, Ontario M2J 1V1, Canada.
Int J Technol Assess Health Care. 2005 Fall;21(4):480-6. doi: 10.1017/S026646230505066X.
This assessment sought to evaluate the comparative benefit and adverse effect profile of ximelagatran, as well as the clinical issues surrounding its potential use.
We performed a Dialog OneSearch across BIOSIS Previews, EMBASE, MEDLINE, PASCAL, and ToxFile to identify published literature. PubMed and The Cochrane Library were also searched. Gray literature was identified by searching a variety of Web sites of health technology assessment and related agencies and their associated databases. The manufacturer's Canadian office, AstraZeneca, was invited to submit information.
Ximelagatran is the first oral agent from a new class of anticoagulants called direct thrombin inhibitors. Other oral anticoagulants require routine blood monitoring; ximelagatran does not. Ximelagatran has been evaluated in the areas of venous thromboembolism management, particularly after orthopedic surgery, and stroke prevention in patients with atrial fibrillation. Overall, ximelagatran's efficacy appears comparable to other anticoagulants in these clinical settings. Also, bleeding rates were generally similar between ximelagatran and comparators but, as for warfarin, bleeding risk increases with higher ximelagatran doses. In addition, there is no specific antidote to help manage ximelagatran-induced bleeding. Finally, significantly more patients exposed to long-term ximelagatran developed elevated liver enzymes more than three times the upper normal limit, compared with patients on comparator anticoagulants.
Given its apparent simplicity of use, ximelagatran carries the potential to replace, at least in part, anticoagulants currently used in the management of venous thromboembolism or for preventing stroke in atrial fibrillation patients. However, the safety of ximelagatran will not be fully known without further evaluation and surveillance for potential liver toxicity. There is also a need to evaluate its use in special populations such as patients with renal failure and patients using several concurrent medications.
本评估旨在评价希美加群的相对获益和不良反应，以及围绕其潜在应用的临床问题。
我们通过Dialog OneSearch在《生物学文摘数据库》《荷兰医学文摘数据库》《医学索引数据库》《帕斯卡数据库》和《毒物文件数据库》中检索已发表的文献。同时也检索了PubMed和考克兰图书馆。通过搜索各种卫生技术评估和相关机构的网站及其相关数据库来识别灰色文献。邀请了希美加群的生产商阿斯利康加拿大公司提交信息。
希美加群是新型抗凝剂——直接凝血酶抑制剂类中的首个口服制剂。其他口服抗凝剂需要常规血液监测，而希美加群则不需要。希美加群已在静脉血栓栓塞管理领域进行了评估，尤其是在骨科手术后，以及在房颤患者的卒中预防方面。总体而言，在这些临床环境中，希美加群的疗效似乎与其他抗凝剂相当。此外，希美加群和对照药物的出血率总体相似，但与华法林一样，希美加群剂量越高，出血风险增加。此外，没有特定的解毒剂来处理希美加群引起的出血。最后，与使用对照抗凝剂的患者相比，长期使用希美加群的患者出现肝酶升高超过正常上限三倍的情况明显更多。
鉴于其明显的使用简便性，希美加群有可能至少部分取代目前用于管理静脉血栓栓塞或预防房颤患者卒中的抗凝剂。然而，在未对潜在肝毒性进行进一步评估和监测的情况下，希美加群的安全性尚不完全清楚。还需要评估其在特殊人群中的应用，如肾衰竭患者和同时使用多种药物的患者。
