急性冠状动脉综合征患者和非急性冠状动脉综合征患者降级至替卡格雷单药治疗与 12 个月双联抗血小板治疗的比较:随机试验的系统回顾和单个患者层面的荟萃分析。

IF 98.4 1区 医学 Q1 MEDICINE, GENERAL & INTERNAL
The Lancet Pub Date : 2024-09-07 Epub Date: 2024-08-31 DOI:10.1016/S0140-6736(24)01616-7
Marco Valgimigli, Sung-Jin Hong, Felice Gragnano, Konstantina Chalkou, Anna Franzone, Bruno R da Costa, Usman Baber, Byeong-Keuk Kim, Yangsoo Jang, Shao-Liang Chen, Gregg W Stone, Joo-Yong Hahn, Stephan Windecker, Michael C Gibson, Young Bin Song, Zhen Ge, Pascal Vranckx, Shamir Mehta, Hyeon-Cheol Gwon, Renato D Lopes, George D Dangas, Eùgene P McFadden, Dominick J Angiolillo, Sergio Leonardi, Dik Heg, Paolo Calabrò, Peter Jüni, Roxana Mehran, Myeong-Ki Hong
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引用次数: 0

摘要

背景:急性冠状动脉综合征(ACS)患者冠状动脉支架置入术后的标准治疗是持续 12 个月的双联抗血小板疗法(DAPT)。这项患者个体层面的荟萃分析旨在总结冠状动脉药物洗脱支架植入术后DAPT降级为替卡格雷单药治疗与继续DAPT 12个月的比较证据:我们对具有集中裁定终点的随机试验进行了系统回顾和患者个体数据(IPD)级荟萃分析,以评估在使用冠状动脉药物洗脱支架接受经皮冠状动脉介入治疗的患者中,短期DAPT(2周至3个月)后使用替卡格雷单药治疗(90毫克,一天两次)与12个月DAPT的疗效和安全性比较。在 Ovid MEDLINE、Embase 和两个网站(www.tctmd.com 和 www.escardio.org)上检索了冠状动脉血运重建后 P2Y12 抑制剂单药治疗与 DAPT 比较的随机试验,检索时间从数据库建立之初至 2024 年 5 月 20 日。排除了纳入长期口服抗凝药适应症患者的试验。偏倚风险采用修订后的 Cochrane 偏倚风险工具进行评估。符合条件的试验的主要研究者通过匿名电子数据集提供了IPD。三项排名靠前的主要共同终点是:在按方案治疗人群中检测主要不良心血管或脑血管事件(MACCE;全因死亡、心肌梗死或中风的复合指标)的非劣效性;在意向治疗人群中检测出血学术研究联盟(BARC)3或5次出血和全因死亡的优效性。所有结果均以 Kaplan-Meier 估计值报告。非劣效性测试采用单侧α为0-025,预设非劣效性差值为1-15(危险比[HR]表),然后采用双侧α为0-05进行排序优效性测试。本研究已在 PROSPERO 注册(CRD42024506083):共筛选出 8361 条独特的引文,其中 610 条记录在筛选标题和摘要时被认为可能符合条件。其中,有六项试验将患者随机分配给替卡格雷单药治疗或DAPT。干预后中位数为 78 天(IQR 31-92),中位数治疗时间为 334 天(329-365)。在23 256例按方案治疗的患者中,297例(Kaplan-Meier估计为2%-8%)接受替卡格雷单药治疗的患者发生了MACCE,332例(Kaplan-Meier估计为3%-2%)接受DAPT治疗的患者发生了MACCE(HR 0-91 [95% CI 0-78-1-07];P=0-0039为非劣性;τ22=0-079)和全因死亡(Kaplan-Meier估计值0-9% vs 1-2%;0-76 [0-59-0-98];P=0-034为优越性;τ2解释:我们的研究发现了强有力的证据,与12个月的DAPT相比,降级为替卡格雷单药治疗不会增加缺血风险,并能降低大出血风险,尤其是在ACS患者中。替卡格雷单药治疗还可能降低死亡率,尤其是女性患者,这值得进一步研究:资助机构:提契诺心脏病中心、Ente Ospedaliero Cantonale。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
De-escalation to ticagrelor monotherapy versus 12 months of dual antiplatelet therapy in patients with and without acute coronary syndromes: a systematic review and individual patient-level meta-analysis of randomised trials.

Background: Dual antiplatelet therapy (DAPT) for 12 months is the standard of care after coronary stenting in patients with acute coronary syndrome (ACS). The aim of this individual patient-level meta-analysis was to summarise the evidence comparing DAPT de-escalation to ticagrelor monotherapy versus continuing DAPT for 12 months after coronary drug-eluting stent implantation.

Methods: A systematic review and individual patient data (IPD)-level meta-analysis of randomised trials with centrally adjudicated endpoints was performed to evaluate the comparative efficacy and safety of ticagrelor monotherapy (90 mg twice a day) after short-term DAPT (from 2 weeks to 3 months) versus 12-month DAPT in patients undergoing percutaneous coronary intervention with a coronary drug-eluting stent. Randomised trials comparing P2Y12 inhibitor monotherapy with DAPT after coronary revascularisation were searched in Ovid MEDLINE, Embase, and two websites (www.tctmd.com and www.escardio.org) from database inception up to May 20, 2024. Trials that included patients with an indication for long-term oral anticoagulants were excluded. The risk of bias was assessed using the revised Cochrane risk-of-bias tool. The principal investigators of the eligible trials provided IPD by means of an anonymised electronic dataset. The three ranked coprimary endpoints were major adverse cardiovascular or cerebrovascular events (MACCE; a composite of all-cause death, myocardial infarction, or stroke) tested for non-inferiority in the per-protocol population; and Bleeding Academic Research Consortium (BARC) 3 or 5 bleeding and all-cause death tested for superiority in the intention-to-treat population. All outcomes are reported as Kaplan-Meier estimates. The non-inferiority was tested using a one-sided α of 0·025 with the prespecified non-inferiority margin of 1·15 (hazard ratio [HR] scale), followed by the ranked superiority testing at a two-sided α of 0·05. This study is registered with PROSPERO (CRD42024506083).

Findings: A total of 8361 unique citations were screened, of which 610 records were considered potentially eligible during the screening of titles and abstracts. Of these, six trials that randomly assigned patients to ticagrelor monotherapy or DAPT were identified. De-escalation took place a median of 78 days (IQR 31-92) after intervention, with a median duration of treatment of 334 days (329-365). Among 23 256 patients in the per-protocol population, MACCE occurred in 297 (Kaplan-Meier estimate 2·8%) with ticagrelor monotherapy and 332 (Kaplan-Meier estimate 3·2%) with DAPT (HR 0·91 [95% CI 0·78-1·07]; p=0·0039 for non-inferiority; τ2<0·0001). Among 24 407 patients in the intention-to-treat population, the risks of BARC 3 or 5 bleeding (Kaplan-Meier estimate 0·9% vs 2·1%; HR 0·43 [95% CI 0·34-0·54]; p<0·0001 for superiority; τ2=0·079) and all-cause death (Kaplan-Meier estimate 0·9% vs 1·2%; 0·76 [0·59-0·98]; p=0·034 for superiority; τ2<0·0001) were lower with ticagrelor monotherapy. Trial sequential analysis showed strong evidence of non-inferiority for MACCE and superiority for bleeding among the overall and ACS populations (the z-curve crossed the monitoring boundaries or the required information size without crossing the futility boundaries or approaching the null). The treatment effects were heterogeneous by sex for MACCE (p interaction=0·041) and all-cause death (p interaction=0·050), indicating a possible benefit in women with ticagrelor monotherapy, and by clinical presentation for bleeding (p interaction=0·022), indicating a benefit in ACS with ticagrelor monotherapy.

Interpretation: Our study found robust evidence that, compared with 12 months of DAPT, de-escalation to ticagrelor monotherapy does not increase ischaemic risk and reduces the risk of major bleeding, especially in patients with ACS. Ticagrelor monotherapy might also be associated with a mortality benefit, particularly among women, which warrants further investigation.

Funding: Cardiocentro Ticino Institute, Ente Ospedaliero Cantonale.

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来源期刊
The Lancet
The Lancet 医学-医学:内科
CiteScore
148.10
自引率
0.70%
发文量
2220
审稿时长
3 months
期刊介绍: The Lancet is a world-leading source of clinical, public health, and global health knowledge. It was founded in 1823 by Thomas Wakley and has been an independent, international weekly general medical journal since then. The journal has an Impact Factor of 168.9, ranking first among 167 general and internal medicine journals globally. It also has a Scopus CiteScore of 133·2, ranking it second among 830 general medicine journals. The Lancet's mission is to make science widely available to serve and transform society, positively impacting people's lives. Throughout its history, The Lancet has been dedicated to addressing urgent topics, initiating debate, providing context for scientific research, and influencing decision makers worldwide.
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