韩国首尔大学医院Kyung Woo Park团队研究了基于普拉格雷减量的双重抗血小板策略治疗经皮冠状动脉介入术后急性冠状动脉综合征患者的疗效。2020年8月31日，该成果发表在《柳叶刀》杂志上。

对于接受经皮冠状动脉介入治疗（PCI）的急性冠状动脉综合征患者，建议使用基于P2Y12抑制剂进行双重抗血小板治疗1年以上。该强效药物在早期阶段可最大获益，在慢性维持阶段继续用药存在大出血的风险。因此，减少剂量的抗血小板治疗可能在缺血和出血之间达到最佳平衡。

研究组在韩国35家医院进行了一项随机、开放标签、多中心、非劣效性试验，2014年9月30日至2018年12月18日，共招募了2338例接受PCI的急性冠脉综合征患者。每天接受10mg普拉格雷和100mg阿司匹林治疗1个月后，将其按1：1随机分组，1168例继续接受10mg普拉格雷治疗（常规组），1170例接受5mg普拉格雷治疗（减量组）。

主要终点为1年时的净不良临床事件，包括全因死亡、非致命性心肌梗塞、支架血栓形成、再次血运重建、中风和根据出血学术研究会（BARC）标准分级为2级及以上的出血事件。治疗1年后，减量组中有82例患者（7.2%）发生主要终点，显著低于常规组（10.1%）。与常规组相比，减量组的缺血风险未增加，出血风险则显著降低。

总之，对于急性冠脉综合征患者，PCI后1个月起将普拉格雷剂量减半，因出血减少而缺血未增加，可降低净临床结局风险长达1年。

附：英文原文

Title: Prasugrel-based de-escalation of dual antiplatelet therapy after percutaneous coronary intervention in patients with acute coronary syndrome (HOST-REDUCE-POLYTECH-ACS): an open-label, multicentre, non-inferiority randomised trial

Author: Hyo-Soo Kim, Jeehoon Kang, Doyeon Hwang, Jung-Kyu Han, Han-Mo Yang, Hyun-Jae Kang, Bon-Kwon Koo, Jay Young Rhew, Kook-Jin Chun, Young-Hyo Lim, Jung Min Bong, Jang-Whan Bae, Bong Ki Lee, Kyung Woo Park

Issue&Volume: 2020-08-31

Abstract: Background

A potent P2Y12 inhibitor-based dual antiplatelet therapy is recommended for up to 1 year in patients with acute coronary syndrome receiving percutaneous coronary intervention (PCI). The greatest benefit of the potent agent is during the early phase, whereas the risk of excess bleeding continues in the chronic maintenance phase. Therefore, de-escalation of antiplatelet therapy might achieve an optimal balance between ischaemia and bleeding. We aimed to investigate the safety and efficacy of a prasugrel-based dose de-escalation therapy.

Methods

HOST-REDUCE-POLYTECH-ACS is a randomised, open-label, multicentre, non-inferiority trial done at 35 hospitals in South Korea. We enrolled patients with acute coronary syndrome receiving PCI. Patients meeting the core indication for prasugrel were randomly assigned (1:1) to the de-escalation group or conventional group using a web-based randomisation system. The assessors were masked to the treatment allocation. After 1 month of treatment with 10 mg prasugrel plus 100 mg aspirin daily, the de-escalation group received 5 mg prasugrel, while the conventional group continued to receive 10 mg. The primary endpoint was net adverse clinical events (all-cause death, non-fatal myocardial infarction, stent thrombosis, repeat revascularisation, stroke, and bleeding events of grade 2 or higher according to Bleeding Academic Research Consortium [BARC] criteria) at 1 year. The absolute non-inferiority margin for the primary endpoint was 2·5%. The key secondary endpoints were efficacy outcomes (cardiovascular death, myocardial infarction, stent thrombosis, and ischaemic stroke) and safety outcomes (bleeding events of BARC grade ≥2). The primary analysis was in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, NCT02193971.

Results

From Sept 30, 2014, to Dec 18, 2018, 3429 patients were screened, of whom 1075 patients did not meet the core indication for prasugrel and 16 were excluded due to randomisation error. 2338 patients were randomly assigned to the de-escalation group (n=1170) or the conventional group (n=1168). The primary endpoint occurred in 82 patients (Kaplan-Meier estimate 7·2%) in the de-escalation group and 116 patients (10·1%) in the conventional group (absolute risk difference 2·9%, p non-inferiority<0·0001; hazard ratio 0·70 [95% CI 0·52–0·92], p equivalence=0·012). There was no increase in ischaemic risk in the de-escalation group compared with the conventional group (0·76 [0·40–1·45]; p=0·40), and the risk of bleeding events was significantly decreased (0·48 [0·32–0·73]; p=0·0007).

Interpretation

In east Asian patients with acute coronary syndrome patients receiving PCI, a prasugrel-based dose de-escalation strategy from 1 month after PCI reduced the risk of net clinical outcomes up to 1 year, mainly driven by a reduction in bleeding without an increase in ischaemia.

DOI: 10.1016/S0140-6736(20)31791-8

Source: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)31791-8/fulltext