Meyer Dos Santos Sascha, Harder Sebastian
Department of Clinical Pharmacology, University Hospital Frankfurt, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany.
Drug Saf. 2014 May;37(5):295-307. doi: 10.1007/s40264-014-0151-1.
Non-valvular atrial fibrillation (NVAF) is the most common clinically significant cardiac arrhythmia and is a common cause of stroke. The direct thrombin inhibitor dabigatran etexilate is approved for a variety of indications requiring anticoagulation, including stroke prevention in NVAF. Dabigatran does not require routine monitoring and exhibits only a few drug-drug interactions; however, impaired renal function needs observation. The Randomized Evaluation of Long-Term Anticoagulation Therapy (RE-LY) study comprised about 18,000 patients with NVAF who received dabigatran 110 mg twice daily or 150 mg twice daily, or dose adjusted warfarin. Compared with warfarin, dabigatran 110 mg twice daily was associated with similar rates of stroke and systemic embolism, and lower rates of haemorrhage. Dabigatran 150 mg twice daily was associated with lower rates of stroke and systemic embolism but similar rates of haemorrhage. The rate of intracerebral haemorrhage (ICH) was significantly lower in both dabigatran arms. Basing on the results of the RE-LY study, the net clinical benefit balancing stroke against ICH has been estimated with various settings (study data, registry patients). In patients with low stroke risk but at high risk of bleeding, only dabigatran 110 mg twice daily had a positive net clinical benefit when compared with warfarin. In patients with higher stroke risks, both doses of dabigatran (110 and 150 mg twice daily) had a positive net clinical benefit even if the bleeding risk was high. Registry data after approval of dabigatran indicate similar stroke/systemic embolism and major bleeding rates with dabigatran (both doses) compared with warfarin. Pharmacovigilance sources prove the anticipated bleeding risk, but a refined analysis of such data showed that bleeding rates associated with dabigatran use did not appear to be higher than those associated with warfarin. Dabigatran confers an advantage over warfarin regarding stoke prevention without the burden of the surveillance of vitamin K antagonists, especially in patients with high stroke risk. However, in elderly patients with impaired renal function or considerable bleeding risks, label advice regarding dosing needs strict observation.
非瓣膜性心房颤动（NVAF）是临床上最常见的具有重要意义的心律失常，也是中风的常见病因。直接凝血酶抑制剂达比加群酯已被批准用于多种需要抗凝治疗的适应症，包括预防NVAF患者中风。达比加群不需要常规监测，且仅有少数药物相互作用；然而，肾功能受损时需要密切观察。长期抗凝治疗随机评估（RE-LY）研究纳入了约18000例NVAF患者，这些患者接受每日两次110mg或150mg达比加群治疗，或剂量调整后的华法林治疗。与华法林相比，每日两次110mg达比加群的中风和全身性栓塞发生率相似，但出血发生率较低。每日两次150mg达比加群的中风和全身性栓塞发生率较低，但出血发生率相似。两个达比加群组的脑出血（ICH）发生率均显著较低。基于RE-LY研究的结果，已在各种情况下（研究数据、登记患者）评估了平衡中风与ICH的净临床获益。在中风风险低但出血风险高的患者中，与华法林相比，仅每日两次110mg达比加群具有积极的净临床获益。在中风风险较高的患者中，即使出血风险高，两种剂量的达比加群（每日两次110mg和150mg）均具有积极的净临床获益。达比加群获批后的登记数据显示，与华法林相比，达比加群（两种剂量）的中风/全身性栓塞和大出血发生率相似。药物警戒来源证实了预期的出血风险，但对此类数据的精细分析表明，使用达比加群的出血发生率似乎并不高于使用华法林的出血发生率。在预防中风方面，达比加群优于华法林，且无需承担维生素K拮抗剂监测的负担，尤其是在中风风险高的患者中。然而，在肾功能受损或出血风险较高的老年患者中，关于给药的标签建议需要严格遵守。
