引言

• 2023 年欧洲心脏病学会（ESC）急性冠状动脉综合征（ACS）管理指南推荐默认双联抗血小板治疗（DAPT）方案为强效 P2Y₁₂ 受体抑制剂（普拉格雷或替格瑞洛）联合阿司匹林治疗 12 个月
• 本共识文件旨在补充 ESC 指南，为临床医生选择合适的抗血小板策略提供实用建议

定义

• 缩短或缩写 DAPT 指 DAPT 疗程少于 12 个月
• DAPT 降阶指在常规 DAPT 短期治疗后，使用效力较弱的 P2Y₁₂ 抑制剂
• 标准 DAPT 指 ACS 后 1 年内阿司匹林联合替格瑞洛或普拉格雷治疗

标准 DAPT 治疗 ACS 的证据回顾

• 国际指南推荐 ACS 后 DAPT 治疗 12 个月，联合阿司匹林和 P2Y₁₂ 抑制剂（氯吡格雷、普拉格雷或替格瑞洛）
• 2023 年 ESC 指南推荐替格瑞洛和普拉格雷优于氯吡格雷
• 氯吡格雷适用于高出血风险（HBR）患者或与口服抗凝药（OAC）联合使用的患者

缺血事件评估

标准 DAPT 治疗下缺血事件发生率

• 标准 DAPT 治疗下，ACS 后第 1 年 5 - 10% 的患者发生缺血事件
• 药物洗脱支架治疗的 ACS 患者，第 1 年支架血栓形成（ST）发生率为 1 - 2%，约 70% 发生在第 1 个月内

缺血事件的临床、解剖或手术风险因素

• 临床风险因素：年龄、糖尿病、复发性心肌梗死史、多支冠状动脉疾病等
• 解剖/围手术期因素：植入多个支架、治疗多个病变、总支架长度 >60mm 等

缺血风险生物标志物

• 血小板功能测试（PFT）、C 反应蛋白（CRP）等生物标志物与缺血风险相关，但目前未证明可用于指导 DAPT 降阶或缩短疗程

缺血风险评分

• 多种风险评分用于预测 ACS 患者临床结局，但未证明可改善临床结局或指导抗栓治疗策略

出血事件评估

标准 DAPT 治疗下出血事件发生率

• 非冠状动脉旁路移植术（CABG）相关的大出血发生率为 2 - 5%，12 个月内所有出血发生率可达 35 - 40%

出血的临床、解剖或手术风险因素

• 临床风险因素：虚弱、老年、女性、低体重、慢性肾脏病（CKD）等
• PCI 相关因素：股动脉入路、使用辅助抗栓治疗等

出血风险生物标志物

• GDF - 15、入院时白细胞计数、红细胞分布宽度、天冬氨酸转氨酶水平等与出血风险相关

出血风险评分

• 多种出血风险评分已被评估，但均未在大型随机对照试验中进行前瞻性验证，其在改善患者结局方面的价值尚不清楚

出血和缺血风险的联合评估

• ACS 患者的出血和缺血风险在急性期和长期二级预防中相互交织
• 急性心肌梗死后，出血和缺血事件在急性期后均显著下降，但趋势不同
• 个体出血和缺血风险差异需要个性化的抗血小板策略

降低出血风险的治疗选择

P2Y₁₂ 抑制剂出血风险差异

• 普拉格雷或替格瑞洛联合阿司匹林的出血风险高于氯吡格雷
• Adding $P2Y_{12}$ inhibitor to aspirin increases bleeding risk
• Prasugrel or ticagrelor has higher bleeding risk than clopidogrel
  • CURE trial: clopidogrel increased GUSTO major bleeding vs. placebo (3.7% vs. 2.7%; P=0.001)
  • TRITON - TIMI 38: prasugrel increased TIMI major, life - threatening, and fatal bleeding vs. clopidogrel
  • PLATO trial: ticagrelor increased non - CABG - related TIMI major bleeding, including more fatal intracranial bleeding

缩写 DAPT 后阿司匹林单药治疗

• 13 项随机对照试验表明，缩写 DAPT 后阿司匹林单药治疗可降低出血风险
• Thirteen RCTs compared abbreviated DAPT (1 - 6 months) followed by aspirin monotherapy with standard DAPT after PCI
• Appeared to consistently reduce bleeding risk
  • RESET (2012): 3 - month DAPT non - inferior for primary endpoint, no significant major bleeding difference
  • EXCELLENT (2012): 6 - month DAPT non - inferior, numerical trend of increased ST in abbreviated arm
  • OPTIMIZE (2013): 3 - month DAPT non - inferior, no significant differences in major bleeding or MACE
  • SECURITY (2014): 6 - month DAPT met non - inferiority, no significant difference in secondary endpoint
  • ITALIC (2015): 6 - month DAPT non - inferior, no significant differences in secondary endpoints
  • I - LOVE - IT 2 (2016): 6 - month DAPT reached non - inferiority, no significant difference in composite endpoints
  • IVUS - XPL (2016): no difference between abbreviated and standard DAPT for primary endpoint, no significant secondary differences
  • NIPPON (2017): 6 - month DAPT achieved non - inferiority, no significant secondary differences
  • DAPT - STEMI (2018): 6 - month DAPT non - inferior, no significant TIMI major bleeding difference
  • OPTIMA - C (2018): 6 - month DAPT non - inferior, no TIMI major bleeding events in each arm
  • SMART DATE (2018): 6 - month DAPT non - inferior, significant increase in MI rates
  • REDUCE (2019): 3 - month DAPT non - inferior, no significant BARC ≥2 bleeding difference
  • One - Month DAPT (2021): 1 - month DAPT non - inferior, no significant major bleeding or ischaemic outcome differences

缩写 DAPT 后 P2Y₁₂ 抑制剂单药治疗

• Twelve RCTs compared short DAPT (16 days - 3 months) followed by $P2Y_{12}$ inhibitor monotherapy with standard DAPT in ACS patients
• Aspirin withdrawal associated with lower major bleeding risk
  • Sidney - 2 Collaboration: $P2Y_{12}$ inhibitor monotherapy reduced BARC 3 or 5 bleeding risk by 60% vs. DAPT
  • STOPDAPT - 3: prasugrel monotherapy non - inferior for cardiovascular events, signal for excess ischaemic risk
  • NEOMINDSET trial: early aspirin withdrawal reduced bleeding but not non - inferior to 12 - month DAPT, increased death and ischaemic events
• Protection from ischaemic events may differ based on $P2Y_{12}$ inhibitor type
  • Ticagrelor monotherapy: may reduce mortality risk vs. DAPT with aspirin and clopidogrel
  • Clopidogrel monotherapy: composite endpoint exceeded non - inferiority boundaries due to excess MI
  • Prasugrel monotherapy: limited and inconclusive evidence
  • GLOBAL LEADERS ACS subgroup (2018): abbreviated DAPT not superior for primary endpoint, reduced BARC ≥3 bleeding
  • SMART - CHOICE (2019): abbreviated DAPT achieved non - inferiority, reduced BARC ≥2 bleeding
  • TWILIGHT - ACS (2020): abbreviated DAPT superior for BARC ≥2 bleeding, no difference in secondary endpoint
  • TICO (2020): abbreviated DAPT reduced primary endpoint rates, reduced TIMI major bleeding
  • MASTER DAPT (2021): abbreviated DAPT non - inferior for primary endpoints, reduced BARC ≥2 bleeding
  • STOPDAPT - 2 ACS (2022): abbreviated DAPT failed to reach non - inferiority, increased MI rates, reduced TIMI bleeding
  • T - PASS (2024): abbreviated DAPT achieved non - inferiority and superiority, reduced BARC ≥3 bleeding
  • ULTIMATE DAPT (2024): abbreviated DAPT reduced BARC ≥2 bleeding, achieved non - inferiority for MACE
  • HOST - BR (2025): in non - HBR stratum, 3 - month DAPT non - inferior for NACE and MACCE, superior for bleeding; in HBR stratum, 1 - month DAPT did not reach non - inferiority for NACE
  • 4D - ACS trial (2025): abbreviated DAPT achieved non - inferiority and superiority, reduced bleeding
  • NEO - MINDSET trial (2025): SAPT with potent $P2Y_{12}$ inhibitor did not achieve non - inferiority
  • TARGET - FIRST trial (2025): abbreviated DAPT achieved non - inferiority and superiority, reduced BARC type 2, 3, or 5 bleeding

双联抗血小板治疗强度降级

血小板功能测试指导

• PFT可预测出血、支架血栓形成和死亡率，允许体外测量血小板反应性
• 试验探索PFT强化抗血小板治疗无临床获益
• PFT指导的P2Y₁₂抑制剂降级可降低出血风险，保留缺血保护
• 两项研究探索ACS患者PFT指导DAPT降级：ANTARCTIC试验未改善净临床结局；TROPICAL - ACS试验显示PFT指导降级与普拉格雷标准治疗1年净临床获益非劣效

基因分型指导

• 氯吡格雷是前药，CYP2C19基因多态性影响其代谢
• Popular Genetics试验：基因型指导的P2Y₁₂抑制降级策略与标准DAPT对比，基因型指导组在PLATO出血方面优于标准治疗组，复合终点数值更低但无统计学意义

非指导降级

• 三项RCT对比非指导降级与标准DAPT：TOPIC试验、HOST - REDUCE - POLYTECH - ACS试验、TALOS - AMI试验均显示非指导降级可降低出血风险，不增加缺血事件
• 网络荟萃分析：非指导降级出血减少幅度大于指导降级

其他减少出血措施

• 常规径向动脉入路，尽可能推迟非紧急侵入性操作，优化控制血压
• 避免同时使用血小板抑制剂，必要时更换非甾体药物
• 高胃肠道出血风险DAPT患者建议使用质子泵抑制剂，避免奥美拉唑和埃索美拉唑与氯吡格雷联用
• 考虑患者情况，虚弱或重症患者可能需不同治疗方法

降低缺血风险的治疗选择

急性冠状动脉综合征后第一年极低剂量利伐沙班

• 原理：利伐沙班减少凝血酶生成，可能减少缺血事件，但不改善纤溶
• ATLAS ACS 2 - TIMI 51试验：VLDR加DAPT降低心血管死亡风险，但大出血增加四倍；STEMI亚组风险估计相似；早期ACS缺血风险为主，VLDR可能有短期应用窗口；有研究建议稳定ACS患者PCI后用VLDR替代阿司匹林

一年后延长双联抗栓治疗选择

• CHARISMA试验：阿司匹林加氯吡格雷未显著降低MACE，但对有心肌梗死、中风或症状性外周动脉疾病患者有益
• DAPT试验：PCI后延长噻吩吡啶治疗降低ST或MACE风险，但全因死亡略高
• PEGASUS - TIMI 54试验：阿司匹林基础上加用替格瑞洛降低MACE，增加出血，对无HBR患者有益，高缺血风险无HBR患者心血管死亡率降低
• COMPASS试验：阿司匹林加利伐沙班降低MACE，但大出血增加；利伐沙班单药未改善心血管结局，出血增加

基于出血风险的个性化双联抗血小板治疗

• HOST - BR研究：按ARC标准分层出血风险评估PCI术后患者最佳DAPT时长
  • HBR组：随机分配1或3个月DAPT
  • 非HBR组：随机分配3或12个月DAPT
  • 结果：HBR患者1个月DAPT缺血事件多；非HBR患者3个月DAPT不劣于12个月DAPT，且出血更优

短程双联抗血小板治疗后单药治疗

• 无阿司匹林与P2Y₁₂抑制剂单药对比试验
• 网络荟萃分析：与阿司匹林和氯吡格雷DAPT相比，阿司匹林单药12个月出血显著降低；氯吡格雷或替格瑞洛单药与阿司匹林相比出血无显著增加
• 短程DAPT后P2Y₁₂抑制剂单药（尤其替格瑞洛）12个月内外心梗风险更低；替格瑞洛单药12个月内心梗显著降低且不增加出血
• GLOBAL LEADERS试验亚组分析：PCI术后第二年替格瑞洛单药缺血事件风险降低，但出血增加

特定人群建议

种族

• 不同种族凝血 - 纤溶轴和炎症异常不同，非洲裔美国人动脉血栓形成风险最高，东亚人最低
• 荟萃分析：“降级DAPT策略”在东亚和白种人患者中临床获益不同；东亚患者降低DAPT强度可减少出血无安全问题，白种人可能有缺血风险；缩短DAPT时长减少净不良临床事件，主要在东亚患者中减少大出血

生物学性别

• 女性ACS患者年龄大、合并症多，诊断晚，抗血小板治疗启动延迟
• 抗栓药物在男女中疗效相似，DAPT降级或缩短治疗无性别差异
• 女性抗栓药物剂量可能过高，股动脉入路多，出血率高，HBR比例高

个体化抗栓策略实用建议

平均缺血和出血风险

• 2023 ESC guidelines recommend 12 - month DAPT as default (except HBR), based on pivotal RCTs
• More potent $P2Y_{12}$ inhibitors (prasugrel, ticagrelor) recommended over clopidogrel
• For event - free patients after 3 - 6 months of DAPT and not at high ischaemic risk, ESC suggests single antiplatelet therapy (preferably $P2Y_{12}$ inhibitor)
• Some experts advocate 1 - 3 months of DAPT followed by ticagrelor single antiplatelet therapy based on RCTs and meta - analyses

缺血风险超过出血风险

• 2023 ESC guidelines recommend 12 - month DAPT for high ischaemic and low bleeding risk patients
• Consider continuation of a second antithrombotic agent for extended long - term secondary prevention
• For increased ischaemic risk and low bleeding risk, long - term DAPT after 1 year may be appropriate, e.g., aspirin + ticagrelor 60 mg twice daily
• In selected high - risk individuals, extended dual antithrombotic therapy (aspirin + VLDR) may be appropriate

出血风险超过缺血风险

• Abbreviate or de - escalate initial DAPT in HBR patients
• Abbreviating DAPT and continuing single antiplatelet therapy (aspirin after 3 - 6 months or $P2Y_{12}$ inhibitor after 1 - 3 months) reduces bleeding without increasing ischaemic events
• De - escalating DAPT by switching potent $P2Y_{12}$ inhibitors to clopidogrel (routinely after 1 - 3 months or guided by genetic tests after 1 - 4 weeks) decreases bleeding without increasing ischaemic events
• Avoid prolonged DAPT or aspirin + VLDR beyond 12 months

高缺血和高出血风险

• High ischaemic and bleeding risk co - exist in 5 - 10% of patients, up to 55% in complex PCI
• $P2Y_{12}$ inhibitor monotherapy after 1 - 3 months of DAPT has similar fatal and ischaemic event rates and lower major bleeding risk
• HBR should be prioritized to guide DAPT duration decision - making
• Extended DAPT strategies may not benefit HBR/HIR patients

低缺血和低出血风险

• Current guidelines recommend 12 - month standard DAPT (aspirin + prasugrel/ticagrelor)
• Consider DAPT abbreviation or de - escalation as bleeding risk may outweigh ischaemic risk

结论

• Personalize DAPT duration and intensity for ACS patients post - PCI based on thrombotic and bleeding risks
• Consider alternative DAPT regimens due to bleeding reduction, low late - phase risk with new DES, and high HBR prevalence
• Focus on managing modifiable risk, with bleeding risk dominating DAPT decision - making
• Follow clinical consensus statements to minimize events and improve outcomes

临床共识声明

ACS的标准DAPT治疗

• Current guidelines recommend 12 - month DAPT as standard/default strategy after ACS

缺血风险评估

• Incidence of ischaemic events with standard DAPT: 5 - 10% in first year, 1 - 2% ST mostly within 30 days
• Ischaemic risk determined by clinical, anatomical, procedural factors, overlapping with bleeding risk factors
• Biomarkers (PFT, CRP) not useful for guiding APT de - escalation/abbreviation
• Further research needed on clinical risk scores for treatment and outcome improvement

出血风险评估

• Incidence of non - CABG - related major bleeding: 2 - 5% in first year, up to a third in HBR
• Bleeding risk determined by clinical, anatomical, procedural factors, overlapping with ischaemic risk factors
• Additional research needed for robust bleeding risk biomarkers
• No reliable validated bleeding risk score for clinical use

最小化出血风险的治疗选择

缩写DAPT

• Early DAPT abbreviation (first month) exposes patients to excess ischaemic risk
• After 3 - 6 months of DAPT, aspirin monotherapy reduces major bleeding in non - HIR patients
• After 1 - 3 months of DAPT, $P2Y_{12}$ inhibitor monotherapy reduces major bleeding
• Ticagrelor preferred for monotherapy after DAPT (except clopidogrel in HBR)
• Ticagrelor monotherapy may be preferable to aspirin in non - HBR patients in first year

DAPT强度降阶

• PFT can identify high - risk patients, but PFT - guided de - escalation doesn't improve outcomes
• Genotype - guided DAPT de - escalation (using clopidogrel in non - CYP2C19 loss - of - function patients) reduces major bleeding
• DAPT de - escalation (unguided/guided) within first month post - ACS reduces bleeding
• Unguided DAPT de - escalation is more practical