Unguided de-escalation from ticagrelor to clopidogrel in stabilised patients with acute myocardial infarction undergoing percutaneous coronary intervention (TALOS-AMI): an investigator-initiated, open-label, multicentre, non-inferiority, randomised trial,The Lancet

当前位置： X-MOL 学术 › Lancet › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Unguided de-escalation from ticagrelor to clopidogrel in stabilised patients with acute myocardial infarction undergoing percutaneous coronary intervention (TALOS-AMI): an investigator-initiated, open-label, multicentre, non-inferiority, randomised trial
The Lancet ( IF 168.9 ) Pub Date : 2021-10-07 , DOI: 10.1016/s0140-6736(21)01445-8
Chan Joon Kim ₁ , Mahn-Won Park ₂ , Min Chul Kim ₃ , Eun-Ho Choo ₄ , Byung-Hee Hwang ₄ , Kwan Yong Lee ₄ , Yun Seok Choi ₅ , Hee-Yeol Kim ₆ , Ki-Dong Yoo ₇ , Doo-Soo Jeon ₈ , Eun-Seok Shin ₉ , Young-Hoon Jeong ₁₀ , Ki-Bae Seung ₄ , Myung Ho Jeong ₃ , Hyeon Woo Yim ₁₁ , Youngkeun Ahn ₃ , Kiyuk Chang ₄ ,

Affiliation

Department of Internal Medicine, Division of Cardiology, Uijeongbu St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
Department of Internal Medicine, Division of Cardiology, Daejeon St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
Department of Cardiology, Chonnam National University Hospital, Ulsan University Hospital, Seoul, South Korea.
Department of Internal Medicine, Division of Cardiology, Seoul St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
Department of Internal Medicine, Division of Cardiology, Yeouido St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
Department of Internal Medicine, Division of Cardiology, Bucheon St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
Department of Internal Medicine, Division of Cardiology, St Vincent's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
Department of Internal Medicine, Division of Cardiology, Incheon St Mary's Hospital, College of Medicine, The Catholic University of Korea, Seoul, South Korea.
Department of Internal Medicine, Division of Cardiology, Ulsan University Hospital, Seoul, South Korea.
Department of Internal Medicine, Division of Cardiology, Gyeongsang National University Changwon Hospital, Changwon, South Korea.
Department of Preventive Medicine, College of Medicine, The Catholic University of Korea, Seoul, South Korea.

Background

In patients with acute myocardial infarction receiving potent antiplatelet therapy, the bleeding risk remains high during the maintenance phase. We sought data on a uniform unguided de-escalation strategy of dual antiplatelet therapy (DAPT) from ticagrelor to clopidogrel after acute myocardial infarction.

Methods

In this open-label, assessor-masked, multicentre, non-inferiority, randomised trial (TALOS-AMI), patients at 32 institutes in South Korea with acute myocardial infarction receiving aspirin and ticagrelor without major ischaemic or bleeding events during the first month after index percutaneous coronary intervention (PCI) were randomly assigned in a 1:1 ratio to a de-escalation (clopidogrel plus aspirin) or active control (ticagrelor plus aspirin) group. Unguided de-escalation without a loading dose of clopidogrel was adopted when switching from ticagrelor to clopidogrel. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, or bleeding type 2, 3, or 5 according to Bleeding Academic Research Consortium (BARC) criteria from 1 to 12 months. A non-inferiority test was done to assess the safety and efficacy of de-escalation DAPT compared with standard treatment. The hazard ratio (HR) for de-escalation versus active control group in a stratified Cox proportional hazards model was assessed for non-inferiority by means of an HR margin of 1·34, which equates to an absolute difference of 3·0% in the intention-to-treat population and, if significant, a superiority test was done subsequently. To ensure statistical robustness, additional analyses were also done in the per-protocol population. This trial is registered at ClinicalTrials.gov, NCT02018055.

Findings

From Feb 26, 2014, to Dec 31, 2018, from 2901 patients screened, 2697 patients were randomly assigned: 1349 patients to de-escalation and 1348 to active control groups. At 12 months, the primary endpoints occurred in 59 (4·6%) in the de-escalation group and 104 (8·2%) patients in the active control group (p_{non-inferiority}<0·001; HR 0·55 [95% CI 0·40–0·76], p_superiority=0·0001). There was no significant difference in composite of cardiovascular death, myocardial infarction, or stroke between de-escalation (2·1%) and the active control group (3·1%; HR 0·69; 95% CI 0·42–1·14, p=0·15). Composite of BARC 2, 3, or 5 bleeding occurred less frequently in the de-escalation group (3·0% vs 5·6%, HR 0·52; 95% CI 0·35–0·77, p=0·0012).

Interpretation

In stabilised patients with acute myocardial infarction after index PCI, a uniform unguided de-escalation strategy significantly reduced the risk of net clinical events up to 12 months, mainly by reducing the bleeding events.

Funding

ChongKunDang Pharm, Medtronic, Abbott, and Boston Scientific.

中文翻译：

在经皮冠状动脉介入治疗 (TALOS-AMI) 稳定的急性心肌梗死患者中，从替格瑞洛到氯吡格雷的非指导性降阶梯：一项由研究者发起的、开放标签、多中心、非劣效性、随机试验

背景

在接受强效抗血小板治疗的急性心肌梗死患者中，维持期出血风险仍然很高。我们寻求关于急性心肌梗死后从替格瑞洛到氯吡格雷的双重抗血小板治疗 (DAPT) 的统一无指导降阶梯策略的数据。

方法

在这项开放标签、评估者隐蔽、多中心、非劣效性、随机试验 (TALOS-AMI) 中，韩国 32 家机构的急性心肌梗死患者接受阿司匹林和替格瑞洛治疗后的第一个月内没有出现严重的缺血或出血事件。经皮冠状动脉介入治疗 (PCI) 以 1:1 的比例随机分配到降阶梯治疗组（氯吡格雷加阿司匹林）或主动控制组（替格瑞洛加阿司匹林）。当从替格瑞洛转换为氯吡格雷时，采用了无负荷剂量氯吡格雷的非引导性降阶梯治疗。主要终点是根据出血学术研究联盟 (BARC) 标准从 1 到 12 个月的心血管死亡、心肌梗死、中风或 2、3 或 5 型出血的复合终点。与标准治疗相比，进行了非劣效性测试以评估降级 DAPT 的安全性和有效性。在分层 Cox 比例风险模型中，降级与积极对照组的风险比 (HR) 通过 1·34 的 HR 边界评估非劣效性，这相当于在 3·0% 的绝对差异意向治疗人群，如果显着，随后进行优效性检验。为了确保统计稳健性，还对符合方案的人群进行了额外的分析。该试验已在 ClinicalTrials.gov 注册，NCT02018055。这相当于意向治疗人群中 3·0% 的绝对差异，如果显着，则随后进行优效性检验。为了确保统计稳健性，还对符合方案的人群进行了额外的分析。该试验已在 ClinicalTrials.gov 注册，NCT02018055。这相当于意向治疗人群中 3·0% 的绝对差异，如果显着，则随后进行优效性检验。为了确保统计稳健性，还对符合方案的人群进行了额外的分析。该试验已在 ClinicalTrials.gov 注册，NCT02018055。

发现

从 2014 年 2 月 26 日到 2018 年 12 月 31 日，从筛选的 2901 名患者中，随机分配了 2697 名患者：1349 名患者进入降级组，1348 名患者进入积极对照组。在 12 个月时，主要终点发生在降阶梯组 59 例（4·6%）和活性对照组 104 例（8·2%）患者（p_非劣效性<0·001；HR 0·55 [95% CI 0·40–0·76]，p_优势=0·0001)。降级组（2·1%）和积极对照组（3·1%；HR 0·69；95% CI 0·42-1）的心血管死亡、心肌梗死或卒中的复合没有显着差异·14, p=0·15)。BARC 2、3 或 5 次复合出血在降级组中发生的频率较低（3·0% vs 5·6%，HR 0·52；95% CI 0·35–0·77，p=0· 0012)。