韩国全南大学Youngkeun Ahn团队联合天主教大学Kiyuk Chang团队研究了接受经皮冠状动脉介入治疗的稳定期急性心肌梗死患者从替卡格雷到氯吡格雷的非指导性降级策略的疗效。2021年10月9日，《柳叶刀》杂志发表了这一成果。

在接受有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。研究组寻求急性心肌梗死后从替卡格雷到氯吡格雷的双重抗血小板治疗（DAPT）的统一非指导性降级策略的临床数据。

在这项开放性、评估者盲、多中心、非劣效性、随机试验中，研究组在韩国32个研究所招募急性心肌梗死患者，在经皮冠状动脉介入治疗（PCI）后的第一个月内接受阿司匹林和替卡格雷治疗，且无重大缺血或出血事件。将其按1:1的比例随机分组，分别接受氯吡格雷+阿司匹林治疗（降级组）或替卡格雷+阿司匹林治疗（主动对照组）。

当从替卡格雷转换为氯吡格雷后，采用无负荷剂量氯吡格雷的非指导性降级。主要终点为治疗1-12个月内心血管死亡、心肌梗死、中风，或出血学术研究协会（BARC）2、3或5型出血的综合指标。进行非劣效性测试，以评估与标准治疗相比，降级DAPT的安全性和有效性。

2014年2月26日至2018年12月31日，在筛选的2901名患者中，2697名被随机分配：其中1349名接受降级治疗，1348名接受主动对照。在12个月时，降级组中有59名患者（4.6%）发生主要终点，显著低于主动对照组的104名（8.2%）。降级组（2.1%）与主动对照组（3.1%）在心血管死亡、心肌梗死或卒中的综合风险方面没有显著差异。降级组的BARC 2、3或5型综合出血发生率为3.0%，显著低于主动对照组的5.6%。

研究结果表明，对于PCI术后病情稳定的急性心肌梗死患者，采用统一的非指导性降级策略显著降低了12个月内净临床事件的风险，主要通过减少出血事件。

附：英文原文

Title: 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

Author: Chan Joon Kim, Mahn-Won Park, Min Chul Kim, Eun-Ho Choo, Byung-Hee Hwang, Kwan Yong Lee, Yun Seok Choi, Hee-Yeol Kim, Ki-Dong Yoo, Doo-Soo Jeon, Eun-Seok Shin, Young-Hoon Jeong, Ki-Bae Seung, Myung Ho Jeong, Hyeon Woo Yim, Youngkeun Ahn, Kiyuk Chang, Chan Joon Kim, Mahn-Won Park, Min Chul Kim, Eun-Ho Choo, Byung-Hee Hwang, Kwan Yong Lee, Yun Seok Choi, Hee-Yeol Kim, Ki-Dong Yoo, Doo-Soo Jeon, Eun-Seok Shin, Yong-Hoon Jeong, Ki-Bae Seung, Myung Ho Jeon, Youngkeun Ahn, Kiyuk Chang, Ju-Hyeon Oh, Sang Jin Ha, Ju Yeol Baek, Kyung Tae Jung, Joon-Hyung Doh, Won Kim, Dong-Bin Kim, Kwang Soo Cha, Myeong-Ho Yoon, Seung-Ho Hur, Seung-Hwan Lee, Byung-Ryul Cho, Jong-Seon Park, Jin Shin Koh, Sang-Hyun Kim, Jang Hyun Cho, Byung Joo Shim, Sang Wook Kim, Jae-Sik Jang, Kee-Sik Kim, Won-Yong Shin, Ki-Chul Sung

Issue&Volume: 2021/10/09

Abstract:

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 (pnon-inferiority<0·001; HR 0·55 [95% CI 0·40–0·76], psuperiority=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.

DOI: 10.1016/S0140-6736(21)01445-8

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01445-8/fulltext