Severance Hospital, Yonsei University College of Medicine, Seoul, Korea (S.-J.H., S.-J.L., Y.-J.L., C.-M.A., J.-S.K., B.-K.K., Y.-G.K., D.C., M.-K.H.).
Myongji Hospital, Hanyang University College of Medicine, Goyang, Korea (Y.S.).
Circulation. 2024 Feb 20;149(8):562-573. doi: 10.1161/CIRCULATIONAHA.123.066943. Epub 2023 Oct 25.
Stopping aspirin within 1 month after implantation of a drug-eluting stent for ticagrelor monotherapy has not been exclusively evaluated for patients with acute coronary syndrome. The aim of this study was to investigate whether ticagrelor monotherapy after <1 month of dual antiplatelet therapy (DAPT) is noninferior to 12 months of ticagrelor-based DAPT for adverse cardiovascular and bleeding events in patients with acute coronary syndrome.
In this randomized, open-label, noninferiority trial, 2850 patients with acute coronary syndrome who underwent drug-eluting stent implantation at 24 centers in South Korea were randomly assigned (1:1) to receive either ticagrelor monotherapy (90 mg twice daily) after <1 month of DAPT (n=1426) or 12 months of ticagrelor-based DAPT (n=1424) between April 24, 2019, and May 31, 2022. The primary end point was the net clinical benefit as a composite of all-cause death, myocardial infarction, definite or probable stent thrombosis, stroke, and major bleeding at 1 year after the index procedure in the intention-to-treat population. Key secondary end points were the individual components of the primary end point.
Among 2850 patients who were randomized (mean age, 61 years; 40% ST-segment-elevation myocardial infarction), 2823 (99.0%) completed the trial. Aspirin was discontinued at a median of 16 days (interquartile range, 12-25 days) in the group receiving ticagrelor monotherapy after <1 month of DAPT. The primary end point occurred in 40 patients (2.8%) in the group receiving ticagrelor monotherapy after <1-month DAPT, and in 73 patients (5.2%) in the ticagrelor-based 12-month DAPT group (hazard ratio, 0.54 [95% CI, 0.37-0.80]; <0.001 for noninferiority; =0.002 for superiority). This finding was consistent in the per-protocol population as a sensitivity analysis. The occurrence of major bleeding was significantly lower in the ticagrelor monotherapy after <1-month DAPT group compared with the 12-month DAPT group (1.2% versus 3.4%; hazard ratio, 0.35 [95% CI, 0.20-0.61]; <0.001).
This study provides evidence that stopping aspirin within 1 month for ticagrelor monotherapy is both noninferior and superior to 12-month DAPT for the 1-year composite outcome of death, myocardial infarction, stent thrombosis, stroke, and major bleeding, primarily because of a significant reduction in major bleeding, among patients with acute coronary syndrome receiving drug-eluting stent implantation. Low event rates, which may suggest enrollment of relatively non-high-risk patients, should be considered in interpreting the trial.
URL: https://www.clinicaltrials.gov; Unique identifier: NCT03797651.
替格瑞洛单药治疗的患者在药物洗脱支架植入后 1 个月内停用阿司匹林尚未专门进行评估。本研究的目的是评估在接受双抗血小板治疗（DAPT）<1 个月后替格瑞洛单药治疗是否不劣于替格瑞洛为基础的 DAPT 12 个月用于急性冠状动脉综合征患者的不良心血管和出血事件。
在这项随机、开放标签、非劣效性试验中，在韩国的 24 个中心接受药物洗脱支架植入的 2850 例急性冠状动脉综合征患者被随机（1:1）分配接受替格瑞洛单药治疗（每日两次 90mg）<1 个月 DAPT（n=1426）或替格瑞洛为基础的 DAPT 12 个月（n=1424），时间为 2019 年 4 月 24 日至 2022 年 5 月 31 日。主要终点是意向治疗人群指数手术后 1 年全因死亡、心肌梗死、确定或可能的支架血栓形成、卒中和主要出血的净临床获益复合终点。关键次要终点是主要终点的各个组成部分。
在 2850 例被随机分组的患者中（平均年龄 61 岁；40%为 ST 段抬高型心肌梗死），2823 例（99.0%）完成了试验。在接受替格瑞洛单药治疗<1 个月 DAPT 的患者中，阿司匹林中位数在 16 天（四分位距，12-25 天）时停药。在接受替格瑞洛单药治疗<1 个月 DAPT 的患者中，主要终点发生在 40 例（2.8%）患者中，在接受替格瑞洛为基础的 12 个月 DAPT 组中发生在 73 例（5.2%）患者中（风险比，0.54[95%CI，0.37-0.80]；<0.001 用于非劣效性；=0.002 用于优越性）。这一发现与敏感性分析作为协议人群一致。与 12 个月 DAPT 组相比，替格瑞洛单药治疗<1 个月 DAPT 组的主要出血发生率显著降低（1.2%比 3.4%；风险比，0.35[95%CI，0.20-0.61]；<0.001）。
这项研究提供的证据表明，替格瑞洛单药治疗在支架植入后 1 个月内停用阿司匹林不仅不劣于替格瑞洛为基础的 DAPT 12 个月，而且在死亡、心肌梗死、支架血栓形成、卒中和主要出血的 1 年复合结局方面优于替格瑞洛为基础的 DAPT，主要是因为主要出血显著减少，在接受药物洗脱支架植入的急性冠状动脉综合征患者中。低事件率可能表明纳入了相对非高危患者，在解释试验时应考虑这一点。
