Occhipinti Giovanni, Laudani Claudio, Galli Mattia, Ortega-Paz Luis, Kunadian Vijay, Mendieta Guiomar, Rinaldi Riccardo, Andreotti Felicita, Mehran Roxana, López-Sobrino Teresa, Capodanno Davide, Angiolillo Dominick J, Sabaté Tenas Manel, Brugaletta Salvatore
Hospital Clínic, Cardiovascular Clinic Institute, Institut d'Investigacions Biomèdiques August Pi i Sunyer (IDIBAPS), University of Barcelona, Barcelona, Spain.
Division of Cardiology, Azienda Ospedaliero-Universitaria Policlinico "Rodolico - San Marco", University of Catania, Catania, Italy.
Eur Heart J. 2025 Jul 11. doi: 10.1093/eurheartj/ehaf473.
Dual antiplatelet therapy (DAPT) de-escalation strategies improve outcomes after percutaneous coronary intervention (PCI) compared to standard DAPT. However, the potential impact of sex on the safety and efficacy of these strategies is yet to be fully investigated.
Randomized controlled trials comparing de-escalated vs standard DAPT regimens in patients without baseline indication for oral anticoagulation reporting outcomes stratified by sex were included. The co-primary endpoints were trial-defined major adverse cardiovascular events (MACE) and major bleeding. Hazard ratios (HR) with 95% confidence intervals (CI) were computed to account for different follow-up durations. A network meta-analysis including ranking of treatments was performed to explore the comparative effects of different DAPT de-escalation strategies among females and males.
Overall, 71 272 patients from 20 trials were included, and 23.3% were female. De-escalation strategies were grouped into (1) DAPT discontinuation, by aspirin or the P2Y12 inhibitor; or (2) P2Y12 inhibitor switch or dose reduction. With DAPT discontinuation vs standard DAPT, a significant interaction between treatment effect and sex was found for both MACE (Pint = .028) and major bleeding (Pint = .015). Indeed, DAPT discontinuation reduced MACE in females (HR, 0.86; 95% CI, 0.75-0.98) but not in males (HR, 1.04; 95% CI 0.93-1.16), while reducing major bleeding in males (HR, 0.60; 95% CI, 0.44-0.82) but not in females (HR, 1.04; 95% CI, 0.76-1.43), compared to standard DAPT. Conversely, no interactions by sex were found with P2Y12 inhibitor switch or dose reduction vs standard DAPT for both MACE (Pint = .668) and major bleeding (Pint = .858). At treatment ranking, aspirin discontinuation ranked best for most outcomes in females, while P2Y12 inhibitor switch to clopidogrel showed the best outcomes in males.
Sex may influence the safety and efficacy of antiplatelet de-escalation strategies after PCI, particularly those involving the shortening of DAPT. Aspirin discontinuation may represent the optimal strategy for females, while P2Y12 inhibitor switch to clopidogrel may be most effective for males.
与标准双联抗血小板治疗（DAPT）相比，DAPT降阶梯策略可改善经皮冠状动脉介入治疗（PCI）后的预后。然而，性别对这些策略的安全性和有效性的潜在影响尚未得到充分研究。
纳入比较无口服抗凝基线指征患者的降阶梯与标准DAPT方案并按性别分层报告结局的随机对照试验。共同主要终点为试验定义的主要不良心血管事件（MACE）和大出血。计算95%置信区间（CI）的风险比（HR）以考虑不同的随访持续时间。进行包括治疗排序的网络荟萃分析，以探讨不同DAPT降阶梯策略在女性和男性中的比较效果。
总体而言，纳入了来自20项试验的71272例患者，其中23.3%为女性。降阶梯策略分为：（1）通过停用阿司匹林或P2Y12抑制剂进行DAPT停药；或（2）P2Y12抑制剂转换或剂量减少。与标准DAPT相比，在DAPT停药时，MACE（Pint = 0.028）和大出血（Pint = 0.015）的治疗效果与性别之间均存在显著交互作用。事实上，与标准DAPT相比，DAPT停药可降低女性的MACE（HR，0.86；95% CI，0.75 - 0.98），但对男性无此效果（HR，1.04；95% CI 0.93 - 1.16），同时可降低男性的大出血发生率（HR，0.60；95% CI，0.44 - 0.82），但对女性无此效果（HR，1.04；95% CI，0.76 - 1.43）。相反，对于MACE（Pint = 0.668）和大出血（Pint = 0.858），在P2Y12抑制剂转换或剂量减少与标准DAPT之间未发现性别交互作用。在治疗排序方面，阿司匹林停药在女性的大多数结局中排名最佳，而P2Y12抑制剂转换为氯吡格雷在男性中显示出最佳结局。
性别可能影响PCI后抗血小板降阶梯策略的安全性和有效性，特别是那些涉及缩短DAPT疗程的策略。停用阿司匹林可能是女性的最佳策略，而P2Y12抑制剂转换为氯吡格雷可能对男性最有效。
