Massachusetts College of Pharmacy and Health Sciences, 179 Longwood Avenue, Boston, MA 02115–5896, USA.
Clin Ther. 2012 Apr;34(4):766-87. doi: 10.1016/j.clinthera.2012.02.022. Epub 2012 Mar 22.
Until recently, warfarin was the only oral anticoagulant available in the United States. Its narrow therapeutic index, interpatient variability in dose response, and drug and food interactions make it difficult to use. Dabigatran etexilate (DE) is a new oral direct thrombin inhibitor that was approved in the US and in Canada for the prevention of thromboembolic events in patients with atrial fibrillation (AF), as well as in Europe and Canada for the prevention of venous thromboembolism (VTE).
To discuss the role of DE for the prevention and treatment of VTE, as well as for the prevention of stroke in patients with AF.
Peer-reviewed clinical trials, review articles, and treatment guidelines were identified from MEDLINE and the Current Contents database (both 1966-February 15, 2012) using the search terms dabigatran, VTE, Afib, pharmacokinetics, pharmacodynamics, pharmacoeconomics, and cost-effectiveness. Citations from available articles were also reviewed for additional references.
For VTE prophylaxis, DE 150 or 220 mg orally daily has demonstrated either superiority or noninferiority to subcutaneous enoxaparin once daily in most studies. However, one study failed to demonstrate noninferiority to subcutaneous enoxaparin dosed BID in the composite end point of VTE, and all-cause mortality. For VTE treatment, DE 150 mg BID orally was shown to be noninferior to warfarin in preventing recurrent events. For AF, DE 150 mg BID orally is superior to warfarin in the prevention of thromboembolism, whereas 110 mg BID is noninferior to warfarin. Pharmacoeconomic analyses performed in the United Kingdom and Ireland found that DE can be cost-saving compared with enoxaparin in the prevention of VTE. Adverse effects of DE reported in clinical studies include dyspepsia (12%-13%) and bleeding (minor bleeding: 6%-22%).
DE exhibited a safety profile and efficacy comparable to enoxaparin for VTE prophylaxis; comparable safety profile and efficacy to warfarin for VTE treatment; and superiority (150 mg BID orally) in the prevention of stroke and systemic embolism compared with warfarin in patients with AF. The relative ease of oral administration, no need for routine monitoring, and lack of significant drug interactions, may favor use of DE over other anticoagulants. However, there is no antidote for DE currently available.
直到最近，华法林一直是美国唯一可用的口服抗凝剂。其治疗指数狭窄、个体间剂量反应的可变性以及药物和食物相互作用使其难以使用。达比加群酯（DE）是一种新型口服直接凝血酶抑制剂，已在美国和加拿大获得批准，用于预防心房颤动（AF）患者的血栓栓塞事件，以及在欧洲和加拿大用于预防静脉血栓栓塞（VTE）。
讨论 DE 在预防和治疗 VTE 以及预防 AF 患者中风方面的作用。
从 MEDLINE 和 Current Contents 数据库（均为 1966 年-2012 年 2 月 15 日）中检索同行评议的临床试验、综述文章和治疗指南，使用的检索词为达比加群、VTE、房颤、药代动力学、药效学、药物经济学和成本效益。还查阅了现有文章的参考文献，以获取更多参考文献。
对于 VTE 预防，DE 150 或 220 mg 每日口服在大多数研究中显示出优于或不劣于每日一次皮下依诺肝素。然而，一项研究未能证明在 VTE 的复合终点和全因死亡率方面优于每日两次皮下依诺肝素。对于 VTE 的治疗，DE 150 mg 每日两次口服在预防复发事件方面不劣于华法林。对于 AF，DE 150 mg 每日两次口服在预防血栓栓塞方面优于华法林，而 110 mg 每日两次口服与华法林相当。在英国和爱尔兰进行的药物经济学分析发现，与依诺肝素相比，DE 可节省 VTE 的预防成本。在临床试验中报告的 DE 的不良反应包括消化不良（12%-13%）和出血（轻微出血：6%-22%）。
DE 在 VTE 预防方面表现出与依诺肝素相当的安全性和疗效；在 VTE 治疗方面与华法林具有相当的安全性和疗效；与华法林相比，在预防 AF 患者中风和全身性栓塞方面具有优越性（150 mg 每日两次口服）。口服给药相对容易，无需常规监测，且无明显药物相互作用，这可能使其优于其他抗凝剂。然而，目前尚无 DE 的解毒剂。
