[文章] 坎格瑞洛与碾碎替格瑞洛在急性心肌梗死合并心源性休克中的比较（DAPT-SHOCK-AMI）：一项随机、双盲试验
完整摘要 · 中文译文
背景：急性心肌梗死合并心源性休克（AMI-CS）可能影响口服P2Y12抑制剂的给药和吸收，并具有高缺血和高死亡风险。本试验评估了静脉注射坎格瑞洛在短期临床结局方面是否非劣于嚼碎口服替格瑞洛，以及它是否在AMI-CS患者中提供更快、更一致的血小板抑制作用。 方法：DAPT-SHOCK-AMI是一项双盲试验，在五个欧洲国家（捷克共和国、法国、德国、波兰和斯洛伐克）的29家医院开展。年龄大于18岁的AMI-CS患者被随机分配（1:1比例，按中心、年龄、性别、是否存在ST段抬高和机械通气进行分层）接受坎格瑞洛（30 μg/kg推注，随后以4 μg/kg每分钟输注至少2小时）或嚼碎替格瑞洛（180 mg负荷剂量）。主要实验室终点为直接经皮冠状动脉介入治疗结束时血小板反应指数低于50%。主要临床终点为30天时的死亡、心肌梗死或缺血性卒中。主要临床终点在所有接受研究治疗的随机分配患者中按预设1个百分点界值进行非劣效性分析。该研究已在ClinicalTrials.gov（NCT03551964）和EudraCT（2018-002161-19）注册；招募和1年随访已完成，5年随访正在进行中。 研究结果：2018年8月1日至2024年1月19日期间，605例患者（137例［23%］为女性）被随机分配至坎格瑞洛组（n=298）或替格瑞洛组（n=307）；1年随访中无存活患者失访。主要实验室终点在坎格瑞洛组56例（19%）患者和替格瑞洛组68例（22%）患者中进行了分析，坎格瑞洛组56例中56例（100%）达到该终点，替格瑞洛组68例中15例（22%）达到该终点（p<0·0001）。30天主要临床终点在坎格瑞洛组298例中112例（38%）发生，替格瑞洛组307例中126例（41%）发生；未证实非劣效性（差异-4个百分点［90% CI -10至3］；非劣效性P=0·13）。30天主要出血在坎格瑞洛组298例中19例（6%）发生，替格瑞洛组307例中16例（5%）发生。 解释：据我们所知，这是首个专门在急性心肌梗死合并心源性休克（AMI-CS）患者中比较P2Y12抑制剂策略的随机试验。在直接经皮冠状动脉介入治疗结束时，坎格瑞洛比碾碎替格瑞洛更频繁地实现有效血小板抑制。对于主要30天临床终点，未证实坎格瑞洛相对于碾碎替格瑞洛的非劣效性。这些试验结果可为未来AMI-CS患者P2Y12抑制策略的试验提供参考。 资助：捷克共和国卫生部、查理大学（捷克共和国）和NextGenerationEU。
完整摘要 · 英文原文
BACKGROUND: Acute myocardial infarction complicated by cardiogenic shock (AMI-CS) can compromise the administration and absorption of oral P2Y12 inhibitors and carries high ischaemic and mortality risks. This trial assessed whether intravenous cangrelor was non-inferior to crushed oral ticagrelor for short-term clinical outcomes and whether it provided faster and more consistent platelet inhibition in patients with AMI-CS. METHODS: DAPT-SHOCK-AMI was a double-blind trial conducted at 29 hospitals across five European countries (Czech Republic, France, Germany, Poland, and Slovakia). Patients older than 18 years with AMI-CS were randomly assigned (1:1 ratio, stratified by centre, age, sex, presence or absence of ST-segment elevation, and mechanical ventilation) to cangrelor (30 μg/kg bolus followed by an infusion of 4 μg/kg per min for at least 2 h) or crushed ticagrelor (180 mg loading dose). The primary laboratory endpoint was a platelet reactivity index of less than 50% at the end of primary percutaneous coronary intervention. The primary clinical endpoint was death, myocardial infarction, or ischaemic stroke at 30 days. The primary clinical endpoint was analysed for non-inferiority with a prespecified margin of 1 percentage point among all randomly assigned patients who received study treatment. The study is registered with ClinicalTrials.gov (NCT03551964) and EudraCT (2018-002161-19); recruitment and 1-year follow-up are complete, and 5-year follow-up is ongoing. FINDINGS: Between Aug 1, 2018, and Jan 19, 2024, 605 patients (137 [23%] were female) were randomly assigned to cangrelor (n=298) or ticagrelor (n=307); no surviving patients were lost to the 1-year follow-up. The primary laboratory endpoint was analysed in 56 (19%) patients in the cangrelor group and 68 (22%) in the ticagrelor group, and was achieved in 56 (100%) of 56 patients receiving cangrelor and 15 (22%) of 68 receiving ticagrelor (p<0·0001). The 30-day primary clinical endpoint occurred in 112 (38%) of 298 patients receiving cangrelor and 126 (41%) of 307 receiving ticagrelor; non-inferiority was not demonstrated (difference -4 percentage points [90% CI -10 to 3]; Pnon-inferiority=0·13). Major bleeding at 30 days occurred in 19 (6%) of 298 patients receiving cangrelor and 16 (5%) of 307 receiving ticagrelor. INTERPRETATION: To our knowledge, this is the first randomised trial to compare P2Y12 inhibitor strategies specifically in patients with AMI-CS. Cangrelor achieved effective platelet inhibition more frequently than crushed ticagrelor at the end of primary percutaneous coronary intervention. Non-inferiority of cangrelor versus crushed ticagrelor was not demonstrated for the primary 30-day clinical endpoint. These trial findings can inform future trials of P2Y12 inhibition strategies in patients with AMI-CS. FUNDING: Czech Republic Ministry of Health, Charles University (Czech Republic), and NextGenerationEU.