British Heart Foundation Glasgow Cardiovascular Research Center, University of Glasgow, Glasgow, United Kingdom; West of Scotland Heart and Lung Center, Golden Jubilee National Hospital, Clydebank, United Kingdom.
West of Scotland Heart and Lung Center, Golden Jubilee National Hospital, Clydebank, United Kingdom.
J Am Coll Cardiol. 2020 Mar 31;75(12):1406-1421. doi: 10.1016/j.jacc.2020.01.041.
Microvascular obstruction affects one-half of patients with ST-segment elevation myocardial infarction and confers an adverse prognosis.
This study aimed to determine whether the efficacy and safety of a therapeutic strategy involving low-dose intracoronary alteplase infused early after coronary reperfusion associates with ischemic time.
This study was conducted in a prospective, multicenter, parallel group, 1:1:1 randomized, dose-ranging trial in patients undergoing primary percutaneous coronary intervention. Ischemic time, defined as the time from symptom onset to coronary reperfusion, was a pre-specified subgroup of interest. Between March 17, 2016, and December 21, 2017, 440 patients, presenting with ST-segment elevation myocardial infarction within 6 h of symptom onset (<2 h, n = 107; ≥2 h but <4 h, n = 235; ≥4 h to 6 h, n = 98), were enrolled at 11 U.K. hospitals. Participants were randomly assigned to treatment with placebo (n = 151), alteplase 10 mg (n = 144), or alteplase 20 mg (n = 145). The primary outcome was the amount of microvascular obstruction (MVO) (percentage of left ventricular mass) quantified by cardiac magnetic resonance imaging at 2 to 7 days (available for 396 of 440).
Overall, there was no association between alteplase dose and the extent of MVO (p for trend = 0.128). However, in patients with an ischemic time ≥4 to 6 h, alteplase increased the mean extent of MVO compared with placebo: 1.14% (placebo) versus 3.11% (10 mg) versus 5.20% (20 mg); p = 0.009 for the trend. The interaction between ischemic time and alteplase dose was statistically significant (p = 0.018).
In patients presenting with ST-segment elevation myocardial infarction and an ischemic time ≥4 to 6 h, adjunctive treatment with low-dose intracoronary alteplase during primary percutaneous coronary intervention was associated with increased MVO. Intracoronary alteplase may be harmful for this subgroup. (A Trial of Low-Dose Adjunctive Alteplase During Primary PCI [T-TIME]; NCT02257294).
微血 管阻塞影响一半的 ST 段抬高型心肌梗死患者，并带来不良预后。
本研究旨在确定在冠状动脉再灌注后早期给予低剂量冠状动脉内阿替普酶的治疗策略的疗效和安全性是否与缺血时间有关。
本研究是一项前瞻性、多中心、平行组、1:1:1 随机、剂量范围试验，纳入接受直接经皮冠状动脉介入治疗的患者。缺血时间定义为从症状发作到冠状动脉再灌注的时间，是一个预先指定的亚组。在 2016 年 3 月 17 日至 2017 年 12 月 21 日期间，在 11 家英国医院共纳入了 440 名症状发作 6 小时内出现 ST 段抬高型心肌梗死的患者（症状发作后 2 小时内，n=107；症状发作后 2 至 4 小时，n=235；症状发作后 4 至 6 小时，n=98）。参与者被随机分配至接受安慰剂（n=151）、阿替普酶 10mg（n=144）或阿替普酶 20mg（n=145）治疗。主要结局是心脏磁共振成像在 2 至 7 天（440 名患者中有 396 名可获得）时测量的微血 管阻塞（左心室质量百分比）的程度。
总体而言，阿替普酶剂量与微血 管阻塞的程度之间没有关联（趋势检验 p 值=0.128）。然而，在缺血时间为 4 至 6 小时的患者中，与安慰剂相比，阿替普酶增加了微血 管阻塞的平均程度：1.14%（安慰剂）与 3.11%（10mg）与 5.20%（20mg）；趋势检验 p 值=0.009。缺血时间和阿替普酶剂量之间的交互作用具有统计学意义（p=0.018）。
对于出现 ST 段抬高型心肌梗死和缺血时间为 4 至 6 小时的患者，在直接经皮冠状动脉介入治疗期间给予低剂量冠状动脉内阿替普酶辅助治疗与微血 管阻塞增加有关。对于这一亚组患者，冠状动脉内阿替普酶可能是有害的。（低剂量阿替普酶辅助直接经皮冠状动脉介入治疗的试验[T-TIME]；NCT02257294）。
