Midwestern College of Pharmacy Glendale, AZ, USA.
Ann Pharmacother. 2013 Apr;47(4):573-7. doi: 10.1345/aph.1R576. Epub 2013 Apr 2.
To determine the safety of dabigatran, rivaroxaban, or apixaban with dual antiplatelet therapy in patients with acute coronary syndromes.
A literature search of MEDLINE (1946-January 2013) was conducted, using the search terms dabigatran, rivaroxaban, or apixaban in combination with dual antiplatelet therapy. A search of literature citations was conducted to identify additional references.
Randomized controlled trials involving the use of one of the new anticoagulants with concomitant dual antiplatelet therapy were included in the review.
Five randomized controlled trials were reviewed, including 1 trial of dabigatran, 2 trials of rivaroxaban, and 2 trials of apixaban. These studies were conducted in patients with a recent acute coronary syndrome, so most patients were receiving aspirin and clopidogrel as dual antiplatelet therapy in addition to a therapeutic dose of one of the anticoagulants. The 3 Phase 2 dose-ranging trials (1 each of dabigatran, rivaroxaban, and apixaban) found an increasing risk of major and clinically relevant nonmajor bleeding with increasing doses of the anticoagulants. The Phase 3 trial of apixaban was terminated early due to an excess of bleeding events, and the trial of rivaroxaban also found an increased risk of bleeding.
The emerging use of dabigatran, rivaroxaban, and apixaban into clinical practice has introduced additional management options, but also safety concerns when combined with antiplatelet agents. Due to the increased risk of bleeding when combining an anticoagulant with 2 antiplatelet agents, clinicians should monitor and educate patients on avoiding potential complications. The need for continued triple regimens should be periodically reviewed.
确定达比加群、利伐沙班或阿哌沙班与双联抗血小板治疗联合用于急性冠状动脉综合征患者的安全性。
通过检索 MEDLINE（1946 年 1 月至 2013 年 1 月），使用达比加群、利伐沙班或阿哌沙班联合双联抗血小板治疗的检索词进行检索。检索文献参考文献以确定其他参考文献。
本综述纳入了涉及新抗凝剂之一与双联抗血小板治疗联合使用的随机对照试验。
综述中评价了 5 项随机对照试验，其中包括 1 项达比加群的试验、2 项利伐沙班的试验和 2 项阿哌沙班的试验。这些研究在近期发生急性冠状动脉综合征的患者中进行，因此大多数患者除了接受治疗剂量的抗凝剂外，还接受阿司匹林和氯吡格雷双联抗血小板治疗。3 项 2 期剂量范围试验（达比加群、利伐沙班和阿哌沙班各 1 项）发现随着抗凝剂剂量的增加，主要和临床上相关的非主要出血风险增加。阿哌沙班的 3 期试验因出血事件过多而提前终止，利伐沙班的试验也发现出血风险增加。
达比加群、利伐沙班和阿哌沙班在临床实践中的新应用带来了更多的治疗选择，但与抗血小板药物联合使用时也存在安全性问题。由于抗凝剂与 2 种抗血小板药物联合使用时出血风险增加，临床医生应监测并教育患者避免潜在并发症。需要定期审查继续三联治疗的必要性。
