Department of Cardiology, Golden Jubilee National Hospital, Glasgow, UK.
Cardiovascular Research Unit, Department of Infection, Immunity and Cardiovascular Disease, University of Sheffield, Sheffield, UK.
Platelets. 2022 Jan 2;33(1):141-146. doi: 10.1080/09537104.2020.1863937. Epub 2020 Dec 26.
Cessation of one component of dual antiplatelet therapy (DAPT) following percutaneous coronary intervention (PCI) has been associated with increased risk of ischemic events but it is uncertain whether discontinuation of aspirin is preferable to discontinuation of the oral P2Y inhibitor. The GLOBAL LEADERS study compared two antiplatelet strategies following PCI, cessation of aspirin at 1 month with continued ticagrelor monotherapy for 23 months versus standard DAPT for 12 months followed by aspirin monotherapy for a further 12 months. We assessed recovery of platelet reactivity after withdrawal of either aspirin or ticagrelor at 1 month and 12 months, respectively, in this study. Platelet aggregation (PA) was assessed before cessation of DAPT ('baseline') and after 2, 7, and 14 days post-cessation using Multiplate whole-blood aggregometry with collagen, thrombin-receptor-activating peptide (TRAP), adenosine diphosphate (ADP) and arachidonic acid (AA) as agonists. Following cessation of aspirin at 1 month, there was marked recovery of PA induced by AA (baseline [mean ± SD]: 11.1 ± 7.4 U vs. 14 days: 64.9 ± 19.6 U, < .0001) and collagen (37.4 ± 22.9 U vs. 79.8 ± 13.8 U, < .0001), whereas PA induced by ADP (18.6 ± 6.6 vs. 69.1 ± 20.5, < .0001) and collagen (34.4 ± 18.7 U vs. 43.0 ± 21.0, = .0018) recovered following cessation of ticagrelor at 12 months. There were no significant changes in TRAP-induced PA in either group. In conclusion, cessation of either component of DAPT leads to substantial increase in platelet reactivity with differential effects on different pathways of platelet activation when aspirin or the P2Y inhibitor is stopped. Further work is required to determine which patients receive net benefit from long-term continuation of DAPT.
停止双联抗血小板治疗（DAPT）的一个组成部分（抗血小板药物），例如经皮冠状动脉介入治疗（PCI）后，会增加缺血事件的风险，但目前尚不确定停止使用阿司匹林是否优于停止使用口服 P2Y 抑制剂。GLOBAL LEADERS 研究比较了 PCI 后的两种抗血小板策略，即 1 个月时停止使用阿司匹林，继续使用替格瑞洛单药治疗 23 个月，与标准的 DAPT 治疗 12 个月后继续使用阿司匹林单药治疗 12 个月。在这项研究中，我们分别在 1 个月和 12 个月时评估了停止使用阿司匹林或替格瑞洛后血小板反应性的恢复情况。血小板聚集（PA）在停止 DAPT 前（“基线”）和停药后 2、7 和 14 天使用 Multiplate 全血聚集仪进行评估，以胶原、血栓素受体激活肽（TRAP）、二磷酸腺苷（ADP）和花生四烯酸（AA）作为激动剂。在 1 个月时停止使用阿司匹林后，AA 诱导的 PA 明显恢复（基线[平均值 ± 标准差]：11.1 ± 7.4 U 比 14 天：64.9 ± 19.6 U，<0.0001）和胶原（37.4 ± 22.9 U 比 79.8 ± 13.8 U，<0.0001），而 ADP（18.6 ± 6.6 vs. 69.1 ± 20.5，<0.0001）和胶原（34.4 ± 18.7 U 比 43.0 ± 21.0 U，=0.0018）诱导的 PA 在 12 个月时停止使用替格瑞洛后恢复。在两组中，TRAP 诱导的 PA 均无明显变化。总之，停止 DAPT 的任何一个组成部分都会导致血小板反应性显著增加，当停止使用阿司匹林或 P2Y 抑制剂时，对不同的血小板激活途径有不同的影响。需要进一步的研究来确定哪些患者从长期 DAPT 中获益。
