C5 补体抑制剂 pexelizumab 对高危冠状动脉旁路移植术结局的影响：PRIMO-CABG I 和 II 试验的联合结果。

Effects of C5 complement inhibitor pexelizumab on outcome in high-risk coronary artery bypass grafting: combined results from the PRIMO-CABG I and II trials.

机构信息

Division of Cardiovascular and Thoracic Surgery, Duke University Medical Center, Durham, NC 27710, USA.

出版信息

J Thorac Cardiovasc Surg. 2011 Jul;142(1):89-98. doi: 10.1016/j.jtcvs.2010.08.035. Epub 2010 Sep 28.

DOI:10.1016/j.jtcvs.2010.08.035

PMID:20880552

Abstract

OBJECTIVE

The previous Pexelizumab for Reduction of Infarction and Mortality in Coronary Artery Bypass Graft Surgery I (PRIMO-CABG I) trial (n = 3099) indicated that C5 complement inhibition with pexelizumab might reduce myocardial infarction (MI) and postoperative mortality. PRIMO-CABG II was designed to investigate the safety and efficacy of terminal complement inhibition in reducing perioperative MI and mortality in patients undergoing CABG surgery who have 2 or more predefined preoperative risk factors.

METHODS

PRIMO-CABG II, a randomized, double-blind, placebo-controlled trial, enrolled 4254 patients undergoing CABG with or without valve surgery at 249 hospitals in North America and Western Europe from June 2004 to July 2005. The patients were randomly assigned to receive intravenous pexelizumab or placebo. The primary composite endpoint was the incidence of death or MI within 30 days of randomization.

RESULTS

The PRIMO-CABG II trial did not meet its prespecified primary endpoint of death or MI at 30 days, the secondary endpoints of death at 30 days, or the development of new or worsening congestive heart failure (relative risk 0.91, 0.82, and 1.01, respectively; P > .05). However, in a combined analysis of both pivotal trials, PRIMO-CABG I and II (n = 7353), death at 30 days was significantly reduced for the greatest risk subset (n = 2156, pexelizumab 5.7% vs placebo 8.1%, P = .024). Furthermore, this mortality reduction persisted throughout the 180-day follow-up period (pexelizumab 11.1% vs placebo 14.4%, P = .036).

CONCLUSIONS

Pexelizumab was associated with a nonsignificant 6.7% reduction in the primary composite endpoint of death or MI at postoperative day 30 in CABG patients enrolled in the PRIMO-CABG II trial, despite the suggestion of a more favorable treatment effect in the previous PRIMO-CABG I trial. However, an exploratory analysis of the combined PRIMO I and II data set using an established predictive risk model showed a mortality benefit for high-risk surgical patients.

摘要

目的

先前的 Pexelizumab 用于降低冠状动脉旁路移植术 I（PRIMO-CABG I）试验中的梗塞和死亡率（n = 3099）表明，C5 补体抑制作用与 pexelizumab 联合使用可能会降低心肌梗死（MI）和术后死亡率。PRIMO-CABG II 旨在研究在接受冠状动脉旁路移植术（CABG）的患者中，在围手术期使用末端补体抑制来降低围手术期 MI 和死亡率的安全性和有效性，这些患者有 2 个或更多预先设定的术前危险因素。

方法

PRIMO-CABG II 是一项随机、双盲、安慰剂对照试验，在 2004 年 6 月至 2005 年 7 月期间，在北美和西欧的 249 家医院中，共纳入 4254 例接受 CABG 手术的患者，包括单纯 CABG 或 CABG 加瓣膜手术。患者被随机分配接受静脉注射 pexelizumab 或安慰剂。主要复合终点是随机分组后 30 天内的死亡或 MI 发生率。

结果

PRIMO-CABG II 试验未达到其预先规定的 30 天内死亡或 MI 的主要终点、30 天内死亡的次要终点，或新发或加重充血性心力衰竭的发展（相对风险分别为 0.91、0.82 和 1.01；P >.05）。然而，在对两项关键性试验（PRIMO-CABG I 和 II，n = 7353）进行的联合分析中，对于风险最高的亚组（n = 2156），30 天的死亡显著降低（pexelizumab 为 5.7%，安慰剂为 8.1%，P =.024）。此外，这种死亡率降低在整个 180 天的随访期间持续存在（pexelizumab 为 11.1%，安慰剂为 14.4%，P =.036）。

结论

尽管在先前的 PRIMO-CABG I 试验中提示治疗效果更有利，但在 PRIMO-CABG II 试验中，接受 CABG 手术的患者中，pexelizumab 术后 30 天的主要复合终点（死亡或 MI）降低了 6.7%。然而，对采用既定预测风险模型的 PRIMO I 和 II 数据综合分析的探索性分析显示，高危手术患者的死亡率获益。