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非 ST 段抬高型急性冠脉综合征的抗血小板和抗凝治疗进展。

Advances in Antiplatelet and Anticoagulant Therapies for NSTE-ACS.

机构信息

Department of Internal Medicine, Duke University Health System, 2301 Erwin Rd, Durham, NC, 27707, USA.

The Duke Clinical Research Institute, Durham, NC, USA.

出版信息

Curr Cardiol Rep. 2019 Jan 12;21(1):3. doi: 10.1007/s11886-019-1090-3.

Abstract

The treatment of patients requiring anticoagulation who develop acute coronary syndrome (ACS) and/or require percutaneous coronary intervention (PCI) must balance the reduction in major adverse cardiovascular events, stroke, and major bleeding. The development of direct oral anticoagulants (DOACs) for the treatment of atrial fibrillation has ushered in an era of potential treatment options for these complex patients. PURPOSE OF REVIEW: To review the clinical evidence underlying the use of DOACs for the treatment of patients with atrial fibrillation and ACS or PCI. RECENT FINDINGS: Three trials studied this particular patient population; WOEST showed that dual therapy with warfarin and clopidogrel decreased hemorrhage at 1 year compared with standard triple therapy (19.4 vs. 44.4% HR 0.36; 95% CI 0.26-0.50; P < 0.0001), without increasing thromboembolic events (11.1 vs. 17.6% HR 0.60; 95% CI 0.38-0.94; P = 0.025). PIONEER AF-PCI showed that 10-15 mg rivaroxaban plus P2Y inhibitor for 12 months significantly lowered bleeding rates than standard triple therapy (16.8 vs. 26.7% HR 0.59; 95% CI 0.47-0.76; P < 0.001) and had equivalent rates of MACE. Finally, REDUAL-PCI compared two different doses of dabigatran (110 mg twice daily and 150 mg twice daily) plus P2Y inhibitor with standard triple therapy and reported reduced ISTH bleeding with both doses; HR 0.52 with 110 mg dabigatran (95% CI 0.42-0.63, P < 0.001) and HR 0.72 with 150 mg dabigatran (95% CI 0.58-0.88; P = 0.002). The rate of the composite of thromboembolic events, death, or unplanned revascularizations was similar between pooled dabigatran dual therapy and triple therapy groups (13.7 vs 13.4% HR 1.04; 95% CI 0.84-1.29; P = 0.005). Recent evidence shows that DOACs plus one antiplatelet agent can decrease bleeding in patients with atrial fibrillation undergoing PCI for ACS. Although not powered to detect non-inferiority or superiority, large studies suggest rivaroxaban 10-15 mg plus P2Y inhibitor for 12 months or dabigatran 150 mg twice daily plus P2y12 inhibitor for 12 months will have similar rates of MACE and stent thrombosis as triple therapy. In patients who have contraindications to DOACs, the strategy of INR-adjusted warfarin plus clopidogrel appears to be safer than warfarin plus dual antiplatelet therapy.

摘要

患者需要抗凝治疗,同时发生急性冠脉综合征(ACS)和/或需要经皮冠状动脉介入治疗(PCI),这两种情况必须兼顾,既要减少主要不良心血管事件、卒中和大出血的发生。直接口服抗凝剂(DOAC)的出现为这些复杂患者的治疗带来了新的选择。

目的

综述 DOAC 在治疗合并 ACS 或 PCI 的房颤患者中的临床应用证据。

新发现

三项研究涉及这一特定患者群体;WOEST 研究表明,与标准三联治疗(19.4%比 44.4%,HR 0.36;95%CI 0.26-0.50;P<0.0001)相比,华法林联合氯吡格雷双重治疗可降低 1 年时的出血事件,而血栓栓塞事件无增加(11.1%比 17.6%,HR 0.60;95%CI 0.38-0.94;P=0.025)。PIONEER AF-PCI 研究表明,利伐沙班 10-15mg 加 P2Y 抑制剂治疗 12 个月可显著降低出血率(16.8%比 26.7%,HR 0.59;95%CI 0.47-0.76;P<0.001),且主要不良心血管事件(MACE)发生率相似。最后,RE-DUAL-PCI 比较了两种不同剂量达比加群(110mg 每日两次和 150mg 每日两次)加 P2Y 抑制剂与标准三联治疗的疗效,两种剂量的达比加群均降低了国际血栓与止血学会(ISTH)出血事件(110mg 达比加群组 HR 0.52;95%CI 0.42-0.63,P<0.001;150mg 达比加群组 HR 0.72;95%CI 0.58-0.88;P=0.002)。达比加群双重治疗组和三联治疗组血栓栓塞事件、死亡或计划外血运重建的复合发生率相似(13.7%比 13.4%,HR 1.04;95%CI 0.84-1.29;P=0.005)。最近的证据表明,DOAC 加一种抗血小板药物可减少合并 ACS 行 PCI 的房颤患者的出血。尽管这些研究未设定非劣效性或优越性检验效能,但大型研究表明,利伐沙班 10-15mg 加 P2Y 抑制剂治疗 12 个月或达比加群 150mg 每日两次加 P2Y12 抑制剂治疗 12 个月与三联治疗的 MACE 和支架血栓形成发生率相似。对于不能应用 DOAC 的患者,华法林加氯吡格雷调整 INR 的策略似乎比华法林加双联抗血小板治疗更安全。

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