JAMA：远程缺血预处理治疗急性卒中：RISTER随机临床试验

2023-10-08 来源：JAMA

本文由小咖机器人翻译整理

期刊来源：JAMA

文献发表时间：2023-10-03

原文链接：https://jamanetwork.com/journals/jama/article-abstract/2810034

关键点内容如下：

问题

联合院前和院内远程缺血预处理（RIC）是否能改善急性缺血性卒中或脑出血患者的功能预后？

调查结果

该随机临床试验纳入了1500名院前疑似卒中患者，与假手术对照相比，RIC治疗并未显著改善确诊卒中患者90天的功能预后（Mrs评分有利变化的优势比为0.95）。

意义

在急性卒中患者中，在院前环境中开始并在医院继续的RIC在90天内没有显著改善功能结果。

摘要内容如下：

重要性

尽管有一些有希望的临床前和临床数据，但仍不确定具有短暂肢体缺血和再灌注周期的远程缺血预处理（RIC）是否是治疗急性卒中的有效方法。

目的

评估在院前环境中开始并在医院中继续进行RIC对急性卒中患者功能结果的影响。

研究设计和参与者

这是一项在丹麦4个卒中中心进行的随机临床试验，纳入了1500名于2018年3月16日至2022年11月11日入组的院前卒中症状（少于4小时的患者。最后一次随访，2023年2月3日）。

干预措施

在1个上肢上使用充气式袖带进行干预（RIC袖带压力，≤200 mm Hg[n=749]，假袖带压力，20 mm Hg[n=751]）。每次治疗应用包括5个循环，每个循环为5分钟的套囊充气，然后是5分钟的套囊放气。在救护车上开始治疗，在医院至少重复一次，然后在参与者的子集中每天重复两次，持续7天。

主要结局和措施

主要终点是在最终诊断为缺血性或出血性卒中的目标人群中，90天时以改良Rankin量表（Mrs）评分（范围为0[无症状]至6[死亡]）的变化来衡量功能结果的改善。

结果

在1500名（中位年龄进行随机分组的患者中，71岁；591名女性[41%]），1433名（96%的）完成了试验。其中，149名患者（10%）被诊断为短暂性脑缺血发作，382名患者（27%）被诊断为卒中模拟。在其余902例目标诊断为卒中的患者（737例[82%]为缺血性卒中，165例[18%]为脑出血）中，436例接受了RIC治疗，466例接受了假治疗。90天时，RIC组的中位Mrs评分为2（IQR，1-3），假手术组为1（IQR，1-3）。在90天时，RIC治疗与改善的功能结果无显著相关性（优势比[OR]，0.95；95%可信区间为0.75~1.20，P=0.67；中位Mrs评分的绝对差值，−1；−1.7至−0.25）。在所有随机分组的患者中，严重不良事件的数量没有显著差异：RIC组有169名患者（23.7%）有1个或多个严重不良事件，而假手术组有175名患者（24.3%）（OR，0.97；95%可信区间为0.85~1.11；P=.68）。RIC组54例（7.2%）和假手术组11例（1.5%）在治疗期间出现上肢疼痛和/或皮肤瘀点。

结论和相关性

在院前环境中开始并在医院中继续的RIC在90天内没有显著改善急性卒中患者的功能结局。

英文原文如下：

Key Points

Question Does combined prehospital and in-hospital remote ischemic conditioning (RIC) improve functional outcome in patients with acute ischemic stroke or intracerebral hemorrhage?

Findings In this randomized clinical trial that included 1500 patients with a suspected stroke in the prehospital setting, RIC treatment, compared with a sham control, did not significantly improve functional outcomes at 90 days in patients with a confirmed diagnosis of stroke (odds ratio for a favorable shift on the mRS score, 0.95).

Meaning Among patients with acute stroke, RIC initiated in the prehospital setting and continued in the hospital did not significantly improve functional outcome at 90 days.

Abstract

Importance Despite some promising preclinical and clinical data, it remains uncertain whether remote ischemic conditioning (RIC) with transient cycles of limb ischemia and reperfusion is an effective treatment for acute stroke.

Objective To evaluate the effect of RIC when initiated in the prehospital setting and continued in the hospital on functional outcome in patients with acute stroke.

Design, Setting, and Participants This was a randomized clinical trial conducted at 4 stroke centers in Denmark that included 1500 patients with prehospital stroke symptoms for less than 4 hours (enrolled March 16, 2018, to November 11, 2022; final follow-up, February 3, 2023).

Intervention The intervention was delivered using an inflatable cuff on 1 upper extremity (RIC cuff pressure, ≤200 mm Hg [n = 749] and sham cuff pressure, 20 mm Hg [n = 751]). Each treatment application consisted of 5 cycles of 5 minutes of cuff inflation followed by 5 minutes of cuff deflation. Treatment was started in the ambulance and repeated at least once in the hospital and then twice daily for 7 days among a subset of participants.

Main Outcomes and Measures The primary end point was improvement in functional outcome measured as a shift across the modified Rankin Scale (mRS) score (range, 0 [no symptoms] to 6 [death]) at 90 days in the target population with a final diagnosis of ischemic or hemorrhagic stroke.

Results Among 1500 patients who were randomized (median age, 71 years; 591 women [41%]), 1433 (96%) completed the trial. Of these, 149 patients (10%) were diagnosed with transient ischemic attack and 382 (27%) with a stroke mimic. In the remaining 902 patients with a target diagnosis of stroke (737 [82%] with ischemic stroke and 165 [18%] with intracerebral hemorrhage), 436 underwent RIC and 466 sham treatment. The median mRS score at 90 days was 2 (IQR, 1-3) in the RIC group and 1 (IQR, 1-3) in the sham group. RIC treatment was not significantly associated with improved functional outcome at 90 days (odds ratio [OR], 0.95; 95% CI, 0.75 to 1.20, P = .67; absolute difference in median mRS score, −1; −1.7 to −0.25). In all randomized patients, there were no significant differences in the number of serious adverse events: 169 patients (23.7%) in the RIC group with 1 or more serious adverse events vs 175 patients (24.3%) in the sham group (OR, 0.97; 95% CI, 0.85 to 1.11; P = .68). Upper extremity pain during treatment and/or skin petechia occurred in 54 (7.2%) in the RIC group and 11 (1.5%) in the sham group.

Conclusions and Relevance RIC initiated in the prehospital setting and continued in the hospital did not significantly improve functional outcome at 90 days in patients with acute stroke.

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