Cardiocentro Ticino Institute, Ente Ospedaliero Cantonale, Lugano, Switzerland (M.V., A.L.).
Faculty of Biomedical Sciences, University of Italian Switzerland, Lugano, Switzerland (M.V., A.L.).
Circulation. 2024 Jul 23;150(4):317-335. doi: 10.1161/CIRCULATIONAHA.124.069012. Epub 2024 Jul 22.
For almost two decades, 12-month dual antiplatelet therapy (DAPT) in acute coronary syndrome (ACS) has been the only class I recommendation on DAPT in American and European guidelines, which has resulted in 12-month durations of DAPT therapy being the most frequently implemented in ACS patients undergoing percutaneous coronary intervention (PCI) across the globe. Twelve-month DAPT was initially grounded in the results of the CURE (Clopidogrel in Unstable Angina to Prevent Recurrent Events) trial, which, by design, studied DAPT versus no DAPT rather than the optimal DAPT duration. The average DAPT duration in this study was 9 months, not 12 months. Subsequent ACS studies, which were not designed to assess DAPT duration, rather its composition (aspirin with prasugrel or ticagrelor compared with clopidogrel) were further interpreted as supportive evidence for 12-month DAPT duration. In these studies, the median DAPT duration was 9 or 15 months for ticagrelor and prasugrel, respectively. Several subsequent studies questioned the 12-month regimen and suggested that DAPT duration should either be fewer than 12 months in patients at high bleeding risk or more than 12 months in patients at high ischemic risk who can safely tolerate the treatment. Bleeding, rather than ischemic risk assessment, has emerged as a treatment modifier for maximizing the net clinical benefit of DAPT, due to excessive bleeding and no clear benefit of prolonged treatment regimens in high bleeding risk patients. Multiple DAPT de-escalation treatment strategies, including switching from prasugrel or ticagrelor to clopidogrel, reducing the dose of prasugrel or ticagrelor, and shortening DAPT duration while maintaining monotherapy with ticagrelor, have been consistently shown to reduce bleeding without increasing fatal or nonfatal cardiovascular or cerebral ischemic risks compared with 12-month DAPT. However, 12-month DAPT remains the only class-I DAPT recommendation for patients with ACS despite the lack of prospectively established evidence, leading to unnecessary and potentially harmful overtreatment in many patients. It is time for clinical practice and guideline recommendations to be updated to reflect the totality of the evidence regarding the optimal DAPT duration in ACS.
近二十年来,美国和欧洲指南中唯一的 I 类推荐一直是急性冠脉综合征(ACS)的 12 个月双联抗血小板治疗(DAPT),这导致全球接受经皮冠状动脉介入治疗(PCI)的 ACS 患者中最常实施 12 个月的 DAPT 治疗。12 个月的 DAPT 最初基于 CURE(氯吡格雷不稳定型心绞痛预防复发事件)试验的结果,该试验的设计是研究 DAPT 与不进行 DAPT 的比较,而不是最佳 DAPT 持续时间。该研究中的平均 DAPT 持续时间为 9 个月,而不是 12 个月。随后的 ACS 研究并非旨在评估 DAPT 持续时间,而是其组成(阿司匹林与普拉格雷或替格瑞洛相比氯吡格雷),被进一步解释为支持 12 个月 DAPT 持续时间的证据。在这些研究中,替格瑞洛和普拉格雷的中位 DAPT 持续时间分别为 9 个月和 15 个月。随后的几项研究对 12 个月的方案提出了质疑,并表明在高出血风险患者中,DAPT 持续时间应少于 12 个月,而在能够安全耐受治疗的高缺血风险患者中,DAPT 持续时间应超过 12 个月。由于高出血风险患者的过度出血和延长治疗方案没有明显获益,出血而不是缺血风险评估已成为最大限度提高 DAPT 净临床获益的治疗调节剂。多种 DAPT 降级治疗策略,包括从普拉格雷或替格瑞洛转换为氯吡格雷、降低普拉格雷或替格瑞洛的剂量以及在维持替格瑞洛单药治疗的同时缩短 DAPT 持续时间,已被一致证明可降低出血风险,而不增加致命或非致命性心血管或脑缺血风险与 12 个月 DAPT 相比。然而,尽管缺乏前瞻性确立的证据,ACS 患者的 12 个月 DAPT 仍然是唯一的 I 类 DAPT 推荐,导致许多患者不必要且可能有害的过度治疗。现在是更新临床实践和指南建议以反映 ACS 中最佳 DAPT 持续时间的全部证据的时候了。