Intracoronary Low-Dose Recombinant Tissue Plasminogen Activator in Primary PCI for ST-Segment Elevation Myocardial Infarction and Large Thrombus Burden: A Randomized Trial.

Targeted, intracoronary delivery of low-dose recombinant tissue plasminogen activator (alteplase) might be an effective strategy for improving microvascular obstruction without increasing the risk of systemic bleeding.

针对性地经冠状动脉内低剂量给予重组组织型纤溶酶原激活剂（阿替普酶）可能是一种有效策略，可以改善微血管阻塞，而不会增加全身性出血的风险。

This study aims to determine whether adjunctive intracoronary delivery of low-dose alteplase reduces microvascular obstruction or major adverse cardiac events (MACE) in patients undergoing primary PCI for STEMI and high thrombus burden.

本研究旨在确定辅助性冠状动脉内低剂量阿替普酶输注是否能减少接受ST段抬高型心肌梗死（STEMI）和高血栓负荷患者初次经皮冠状动脉介入治疗（PCI）的微血管阻塞或主要不良心脏事件（MACE）。

Methods

We performed a multicenter, randomized, double-blindtrial involving patients undergoing primary PCI for large territory STEMI and high thrombus burden.

我们进行了一项多中心、随机、双盲试验，涉及接受大面积ST段抬高型心肌梗死（STEMI）和高血栓负荷患者初次经皮冠状动脉介入治疗（PCI）的患者。

Patients were randomized to receive either alteplase 10 mg, alteplase 20 mg, or placebo (saline) administered directly into the infarct-related artery using a delivery catheter after antegrade reperfusion was established.

患者被随机分配接受 alteplase 10 mg、alteplase 20 mg 或安慰剂（生理盐水）治疗，通过输送导管直接注入梗死相关动脉，在建立前向再灌注后进行。

The primary outcome was the composite of MACE, myocardial blush grade 0/1, distal embolization, or failure to achieve ≥50% ST-segment resolution at 30 minutes post-PCI.

主要结果是 MACE、心肌染色分级 0/1、远端栓塞或在 PCI 后 30 分钟内未能达到 ≥50% ST 段回落的复合指标。

MACE was the composite of cardiovascular death, myocardial re-infarction, cardiogenic shock, or new-onset heart failure at 30 days.

MACE 是心血管死亡、心肌再梗死、心源性休克或30天内新发心力衰竭的复合终点。

Results

Of 210 patients who were randomized, 207 received study drug (n = 68 alteplase 10 mg, n = 69 alteplase 20 mg, and n = 70 placebo).

在随机分配的210名患者中，有207名接受了研究药物治疗（其中68名接受10毫克阿替普酶，69名接受20毫克阿替普酶，70名接受安慰剂）。

The mean age was 62.6 years and 25% were female.

平均年龄为62.6岁，其中25%为女性。

The median time from symptom onset to randomization was 2.9 hours.

从症状发作到随机分组的中位时间为2.9小时。

The primary outcome occurred in 73 patients (53.3%) in the combined alteplase groups vs 37 (52.9%) in the placebo group (relative risk: 1.00; 95% CI: 0.76-1.31; P > 0.99).

主要结果发生在联合使用阿替普酶组的73名患者（53.3%）与安慰剂组的37名患者（52.9%）中（相对风险：1.00；95%置信区间：0.76-1.31；P > 0.99）。

Results were consistent across all components of the primary outcome and for each dose group vs placebo.

在主要结果的所有组成部分以及每个剂量组与安慰剂组的比较中，结果是一致的。

Major or clinically significant bleeding occurred in 1 patient in the trial (in the alteplase 20 mg group).

试验中有一名患者发生了主要或临床显著的出血事件（在20毫克阿替普酶组中）。

During study drug administration, there was a trend to more episodes of ventricular fibrillation in the alteplase groups compared with the placebo group (10.2% vs 1.4%, relative risk: 6.86; 95% CI: 0.91-51.4; P = 0.06).

在研究药物给药期间，与安慰剂组相比，阿替普酶组出现室颤的发作趋势更高（10.2%对比1.4%，相对风险：6.86；95%置信区间：0.91-51.4；P = 0.06）。

Conclusions

Among patients undergoing primary PCI for STEMI and large thrombus burden, intracoronary administration of alteplase was not superior to placebo in reducing the composite primary outcome of MACE at 30 days, myocardial blush grade 0/1, distal embolization, or failure to achieve ≥50% ST-segment resolution.

在进行原发性PCI治疗STEMI和大血栓负荷的患者中，与安慰剂相比，冠状动脉内注射阿替普酶并不能显著降低30天内主要复合终点事件（MACE）的发生率，包括心肌染色分级0/1、远端栓塞或未能实现≥50%的ST段回落。

These data do not support the routine administration of this therapy in patients with STEMI undergoing primary PCI (STRIVE [Adjunctive, Low-dose tPA in Primary PCI for STEMI]; clinicaltrials.gov NCT03335839).

这些数据不支持在进行原发性PCI治疗STEMI的患者中常规使用此疗法（STRIVE [STEMI原发性PCI辅助，低剂量tPA]；clinicaltrials.gov NCT03335839）。