Guided de-escalation of antiplatelet treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention (TROPICAL-ACS): a randomised, open-label, multicentre trial
Guided de-escalation of antiplatelet treatment in patients with acute coronary syndrome undergoing percutaneous coronary intervention (TROPICAL-ACS): a randomised, open-label, multicentre trial
复制标题
DOI：
10.1016/s0140-6736(17)32155-4
复制
发表时间：
2017-10-14
期刊：
影响因子：
168.9
通讯作者：
Investigators, TROPICAL-ACS
中科院分区：
文献类型：
--
作者：
Sibbing, Dirk;Aradi, Daniel;Investigators, TROPICAL-ACS
背景目前的指南推荐在急性冠状动脉综合征经皮冠状动脉介入治疗（PCI）后使用普拉格雷或替格瑞洛有效抑制血小板12个月。然而，强效抗血小板药物相对于效力较低的氯吡格雷的最大抗缺血获益发生在早期，而大多数过量出血事件发生在长期治疗期间。因此，在急性期采用有效的血小板抑制剂，在维持期减量至氯吡格雷的阶段适应性治疗可能是一种替代方法。我们的目的是探讨在血小板功能检测（PFT）指导下，早期将普拉格雷降为氯吡格雷的安全性和有效性。（TROPICAL-ACS）在欧洲的33个研究中心完成，如果患者患有生物标志物阳性的急性冠状动脉综合征并成功进行PCI，并且计划的双重抗血小板治疗持续时间为12个月，则患者被招募。使用基于互联网的随机化程序和计算机生成的区组随机化，将入组的患者随机分配（1：1）至普拉格雷标准治疗12个月（对照组）或递减方案（1周普拉格雷，随后1周氯吡格雷和从出院后第14天开始接受氯吡格雷或普拉格雷的PFT指导维持治疗;指导递减组）。评估者对治疗分配设盲。主要终点为随机化后1年的净临床获益（心血管死亡、心肌梗死、卒中或出血学术研究联盟[BARC]标准规定的2级或以上出血）（非劣效性假设;界值为30%）。本研究在临床试验注册。gov，编号NCT 01959451，和EudraCT，2013-001636- 22。结果2013年12月2日至2016年5月20日期间，2610名患者被分配到研究组; 1304名患者分配到引导降级组，1306名患者分配到对照组。指导性剂量递减组95例患者（7%）和对照组118例患者（9%）发生主要终点（p非劣效性= 0.0004;风险比[HR] 0.81 [95% CI 0.62-1.06]，p优效性= 0.12）。尽管提前降级，但降级组（32例患者[3%]）与对照组（42例患者[3%]; p非劣效性= 0.0115）相比，心血管死亡、心肌梗死或卒中的综合风险未增加。降级组中有64例BARC 2级或以上出血事件（5%），对照组中有79例事件（6%）（HR 0.82 [95%CI 0.59-1.13]; p=0.23）。就净临床获益而言，PCI后1年时，解释指导的抗血小板治疗降级不劣于普拉格雷标准治疗。我们的试验表明，早期降阶梯抗血小板治疗可以被认为是急性冠脉综合征患者PCI治疗的一种替代方法。
Background Current guidelines recommend potent platelet inhibition with prasugrel or ticagrelor for 12 months after an acute coronary syndrome managed with percutaneous coronary intervention (PCI). However, the greatest anti-ischaemic benefit of potent antiplatelet drugs over the less potent clopidogrel occurs early, while most excess bleeding events arise during chronic treatment. Hence, a stage-adapted treatment with potent platelet inhibition in the acute phase and de-escalation to clopidogrel in the maintenance phase could be an alternative approach. We aimed to investigate the safety and efficacy of early de-escalation of antiplatelet treatment from prasugrel to clopidogrel guided by platelet function testing (PFT).Methods In this investigator-initiated, randomised, open-label, assessor-blinded, multicentre trial (TROPICAL-ACS) done at 33 sites in Europe, patients were enrolled if they had biomarker-positive acute coronary syndrome with successful PCI and a planned duration of dual antiplatelet treatment of 12 months. Enrolled patients were randomly assigned (1:1) using an internet-based randomisation procedure with a computer-generated block randomisation with stratification across study sites to either standard treatment with prasugrel for 12 months (control group) or a step-down regimen (1 week prasugrel followed by 1 week clopidogrel and PFT-guided maintenance therapy with clopidogrel or prasugrel from day 14 after hospital discharge; guided de-escalation group). The assessors were masked to the treatment allocation. The primary endpoint was net clinical benefit (cardiovascular death, myocardial infarction, stroke or bleeding grade 2 or higher according to Bleeding Academic Research Consortium [BARC]) criteria) 1 year after randomisation (non-inferiority hypothesis; margin of 30%). Analysis was intention to treat. This study is registered with ClinicalTrials. gov, number NCT01959451, and EudraCT, 2013-001636-22.Findings Between Dec 2, 2013, and May 20, 2016, 2610 patients were assigned to study groups; 1304 to the guided de-escalation group and 1306 to the control group. The primary endpoint occurred in 95 patients (7%) in the guided deescalation group and in 118 patients (9%) in the control group (p non-inferiority = 0.0004; hazard ratio [HR] 0.81 [95% CI 0.62-1.06], p superiority = 0.12). Despite early de-escalation, there was no increase in the combined risk of cardiovascular death, myocardial infarction, or stroke in the de-escalation group (32 patients [3%]) versus in the control group (42 patients [3%]; p non-inferiority = 0.0115). There were 64 BARC 2 or higher bleeding events (5%) in the de-escalation group versus 79 events (6%) in the control group (HR 0.82 [95% CI 0.59-1.13]; p=0.23).Interpretation Guided de-escalation of antiplatelet treatment was non-inferior to standard treatment with prasugrel at 1 year after PCI in terms of net clinical benefit. Our trial shows that early de-escalation of antiplatelet treatment can be considered as an alternative approach in patients with acute coronary syndrome managed with PCI.