Amsterdam UMC-Location Academic Medical Center, Amsterdam, the Netherlands.
Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
J Am Coll Cardiol. 2022 Feb 8;79(5):417-427. doi: 10.1016/j.jacc.2021.11.035.
The use of apixaban instead of vitamin K antagonists (VKA) as well as dropping aspirin results in less bleeding and comparable ischemic events in patients with atrial fibrillation and acute coronary syndrome and/or percutaneous coronary intervention treated with a P2Y inhibitor.
The authors assessed the safety and efficacy of antithrombotic regimens according to HAS-BLED and CHADS-VASc scores in AUGUSTUS (The Open-Label, 2 × 2 Factorial, Randomized, Controlled Clinical Trial to Evaluate the Safety of Apixaban vs. Vitamin K Antagonist and Aspirin vs. Placebo in Patients with Atrial Fibrillation and Acute Coronary Syndrome and/or Percutaneous Coronary Intervention).
In AUGUSTUS, 4,614 patients were randomized in a 2-by-2 factorial design to open-label apixaban or VKA and blinded aspirin or placebo. The primary endpoint was major or clinically relevant nonmajor bleeding over 6 months of follow-up. Cox proportional hazards models were used to assess treatment effects by baseline HAS-BLED (≤2 vs ≥3) and CHADS-VASc (≤2 vs ≥3) scores.
Of 4,386 (95.1%) patients with calculable scores, 66.8% had HAS-BLED ≥3 and 81.7% had CHADS-VASc ≥3. Bleeding rates were lower with apixaban than VKA irrespective of baseline risk (HR: 0.57; 95% CI: 0.41-0.78 [HAS-BLED ≤2]; HR: 0.72; 95% CI: 0.59-0.88 [HAS-BLED ≥3]; interaction P = 0.23). Aspirin increased bleeding irrespective of baseline risk (HR: 1.86; 95% CI: 1.36-2.56 [HAS-BLED ≤2]; HR: 1.81; 95% CI: 1.47-2.23 [HAS-BLED ≥3]; interaction P = 0.88). Apixaban resulted in a lower risk of death or hospitalization than VKA without a significant interaction with baseline stroke risk (HR: 0.92; 95% CI: 0.67-1.25 [CHADS-VASc ≤2]; HR: 0.82; 95% CI: 0.73-0.94 [CHADS-VASc ≥3]; interaction P = 0.53).
Our findings support the use of apixaban and a P2Y inhibitor without aspirin for most patients with atrial fibrillation and acute coronary syndrome and/or percutaneous coronary intervention, irrespective of a patient's baseline bleeding and stroke risk (NCT02415400).
在房颤合并急性冠脉综合征和/或经皮冠状动脉介入治疗的患者中，与维生素 K 拮抗剂（VKA）和阿司匹林相比，使用阿哌沙班可减少出血，缺血性事件发生率相当。
作者评估了 AUGUSTUS 研究（一项评估房颤合并急性冠脉综合征和/或经皮冠状动脉介入治疗患者应用阿哌沙班对比 VKA 以及阿司匹林对比安慰剂的安全性和有效性的开放标签、2×2 析因、随机、对照临床试验）中根据 HAS-BLED 和 CHADS-VASc 评分的抗血栓治疗方案的安全性和有效性。
AUGUSTUS 研究中，4614 例患者以 2×2 析因设计随机分配至开放性阿哌沙班组或 VKA 组，以及盲法阿司匹林组或安慰剂组。主要终点为 6 个月随访期间大出血或临床相关非大出血。采用 Cox 比例风险模型根据基线 HAS-BLED（≤2 分 vs. ≥3 分）和 CHADS-VASc（≤2 分 vs. ≥3 分）评分评估治疗效果。
4386 例（95.1%）可计算评分的患者中，66.8%的患者 HAS-BLED 评分≥3 分，81.7%的患者 CHADS-VASc 评分≥3 分。与 VKA 相比，阿哌沙班无论基线风险如何，均可降低出血风险（HR：0.57；95%CI：0.41-0.78[HAS-BLED≤2]；HR：0.72；95%CI：0.59-0.88[HAS-BLED≥3]；交互 P=0.23）。阿司匹林无论基线风险如何，均可增加出血风险（HR：1.86；95%CI：1.36-2.56[HAS-BLED≤2]；HR：1.81；95%CI：1.47-2.23[HAS-BLED≥3]；交互 P=0.88）。与 VKA 相比，阿哌沙班降低死亡或住院风险的效果更低，但与基线卒中风风险无显著交互作用（HR：0.92；95%CI：0.67-1.25[CHADS-VASc≤2]；HR：0.82；95%CI：0.73-0.94[CHADS-VASc≥3]；交互 P=0.53）。
本研究结果支持在房颤合并急性冠脉综合征和/或经皮冠状动脉介入治疗的患者中，应用阿哌沙班和 P2Y 抑制剂，而无需阿司匹林治疗，且无论患者的基线出血和卒中风风险如何（NCT02415400）。
