Importance Shortened dual antiplatelet therapy followed by potent P2Y12 receptor inhibitor monotherapy reduces bleeding without increasing ischemic events after percutaneous coronary intervention (PCI).

Objective To explore sex differences and evaluate the association of sex with outcomes among patients treated with ticagrelor monotherapy vs ticagrelor plus aspirin.

Design, Setting, and Participants This was a prespecified secondary analysis of TWILIGHT, an investigator-initiated, placebo-controlled randomized clinical trial conducted at 187 sites across 11 countries. Study participants included patients who underwent successful PCI with drug-eluting stents, were planned for discharge with ticagrelor plus aspirin, and who had at least 1 clinical and at least 1 angiographic feature associated with high risk of ischemic or bleeding events. Data were analyzed from May to July 2020.

Interventions At 3 months after PCI, patients adherent to ticagrelor and aspirin without major adverse event were randomized to either aspirin or placebo for an additional 12 months along with ticagrelor.

Main Outcomes and Measures The primary end point was Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding at 12 months after randomization. The primary ischemic end point was a composite of death, myocardial infarction, or stroke.

Results Of 9006 enrolled patients, 7119 underwent randomization (mean [SD] age, 63.9 [10.2] years; 5421 [76.1%] men). Women were older (mean [SD] age, 65.5 [9.6] years in women vs 63.4 [10.3] years in men) with higher prevalence of chronic kidney disease (347 women [21.2%] vs 764 men [14.7%]). The primary bleeding end point occurred more often in women than men (hazard ratio [HR], 1.32; 95% CI, 1.06-1.64; P = .01). After multivariate adjustment, incremental bleeding risk associated with female sex was no longer significant (adjusted HR, 1.20; 95% CI, 0.95-1.52; P = .12). Ischemic end points were similar between sexes. Ticagrelor plus placebo vs ticagrelor plus aspirin was associated with lower risk of BARC type 2, 3, or 5 bleeding in women (adjusted HR, 0.62; 95% CI, 0.42-0.92; P = .02) and men (adjusted HR, 0.57; 95% CI, 0.44-0.73; P < .001; P for interaction = .69). Ischemic end points were similar between treatment groups in both sexes.

Conclusions and Relevance These findings suggest that the higher bleeding risk in women compared with men was mostly attributable to baseline differences, whereas ischemic events were similar between sexes. In this high-risk PCI population, the benefits of early aspirin withdrawal with continuation of ticagrelor were generally comparable in women and men.

Trial Registration ClinicalTrials.gov Identifier: NCT02270242

重要性 缩短双重抗血小板治疗后加用强效 P2Y12 受体抑制剂单药治疗可减少出血，但不会增加经皮冠状动脉介入治疗 (PCI) 后的缺血事件。

目的 探讨替格瑞洛单药治疗与替格瑞洛联合阿司匹林治疗患者的性别差异并评估性别与预后的相关性。

设计、设置和参与者 这是对 TWILIGHT 的预先指定的二次分析，这是一项由研究者发起的、安慰剂对照的随机临床试验，在 11 个国家的 187 个地点进行。研究参与者包括成功接受药物洗脱支架 PCI 的患者，计划使用替格瑞洛加阿司匹林出院，以及具有至少 1 项临床和至少 1 项与缺血或出血事件高风险相关的血管造影特征的患者。数据分析时间为 2020 年 5 月至 2020 年 7 月。

干预 PCI 后 3 个月，依从替格瑞洛和阿司匹林且无重大不良事件的患者被随机分配到阿司匹林或安慰剂组，另外 12 个月与替格瑞洛一起服用。

主要结果和措施 主要终点是随机分组后 12 个月出血学术研究联盟 (BARC) 2、3 或 5 型出血。主要缺血性终点是死亡、心肌梗死或中风的复合终点。

结果 在 9006 名入组患者中，7119 名接受了随机分组（平均 [SD] 年龄，63.9 [10.2] 岁；5421 [76.1%] 名男性）。女性年龄较大（平均 [SD] 年龄，女性 65.5 [9.6] 岁，男性 63.4 [10.3] 岁），慢性肾病患病率较高（347 名女性 [21.2%] vs 764 名男性 [14.7%]）。女性的主要出血终点发生率高于男性（风险比 [HR]，1.32；95% CI，1.06-1.64；P  = .01）。多变量调整后，与女性相关的出血风险增加不再显着（调整后的 HR，1.20；95% CI，0.95-1.52；P = .12)。两性之间的缺血终点相似。替格瑞洛加安慰剂对比替格瑞洛加阿司匹林与女性（校正 HR，0.62；95% CI，0.42-0.92；P  = 0.02）和男性（校正 HR，0.57）的 BARC 2、3 或 5 型出血风险降低相关；95% CI，0.44-0.73；P  < .001；交互作用P = .69）。两性治疗组之间的缺血终点相似。

结论和相关性 这些研究结果表明，与男性相比，女性较高的出血风险主要归因于基线差异，而两性之间的缺血事件相似。在这一高危 PCI 人群中，早期阿司匹林停药和继续替格瑞洛的益处在女性和男性中通常相当。

试验注册 ClinicalTrials.gov 标识符：NCT02270242