Carrier M, Ménasché P, Levy J H, Newman M F, Taylor K M, Haverich A, Chen J C, Shernan S K, Van de Werf F, van der Laan M, Todaro T G, Adams P X, Verrier E D
Montreal Heart Institute, Montreal, Quebec, Canada.
J Thorac Cardiovasc Surg. 2006 Feb;131(2):352-6. doi: 10.1016/j.jtcvs.2005.10.011.
We sought to evaluate the effects of pexelizumab, a C5 complement inhibitor, on death and myocardial infarction in patients undergoing combined aortic valve replacement and coronary artery bypass grafting surgery.
The Pexelizumab for Reduction in Myocardial Infarction and Mortality in Coronary Artery Bypass Graft surgery trial, a phase III prospective, randomized, double-blind, placebo-controlled study, enrolled 3099 patients at 205 centers. The primary end point was the composite of death, myocardial infarction, or both at postoperative day 30 in patients undergoing coronary artery bypass grafting without valve surgery. Postoperative myocardial infarction was defined as a creatine kinase MB fraction value of 100 ng/mL or greater, Q-wave myocardial infarction with a creatine kinase MB fraction value of 70 ng/mL or greater, or new Q-wave evidence of myocardial infarction by postoperative day 30. Because patients undergoing coronary artery bypass grafting with a valve procedure were not included in the primary population, separate analysis of death and myocardial infarction was conducted in 218 patients undergoing combined aortic valve replacement and coronary artery bypass grafting surgery.
Of the 353 patients randomized to any valve procedure, 106 (61%) underwent combined aortic valve replacement and coronary artery bypass grafting in the pexelizumab treatment group compared with 112 (63%) patients in the placebo group. Coronary artery bypass grafting was performed with 1 or more internal thoracic artery grafts in 139 (64%) patients and with 1 or more saphenous vein grafts in 179 (82%) patients. There were 4 (3.8%) deaths in the pexelizumab group versus 11 (9.9%) in the placebo group by postoperative day 30 and 6 (5.7%) deaths in the active group versus 16 (14.4%) in the placebo group by postoperative day 180 (P =.107 and P =.043, respectively, Fisher exact test). The incidence of myocardial infarction 30 days after surgical intervention was identical in the 2 groups, but the study was not designed to detect differences in this cohort of patients.
Inhibition of complement activation by pexelizumab resulted in a decreased mortality at 180 days among 218 patients who underwent combined aortic valve replacement and coronary artery bypass grafting surgery. Additional studies are warranted to confirm this decrease in mortality with pexelizumab in combined aortic valve replacement and coronary artery bypass grafting procedures.
我们旨在评估C5补体抑制剂培昔利珠单抗对接受主动脉瓣置换术和冠状动脉旁路移植术联合手术患者的死亡及心肌梗死的影响。
“冠状动脉旁路移植手术中培昔利珠单抗降低心肌梗死和死亡率”试验，这是一项III期前瞻性、随机、双盲、安慰剂对照研究，在205个中心招募了3099名患者。主要终点是未进行瓣膜手术的冠状动脉旁路移植术患者术后30天时死亡、心肌梗死或两者兼有的复合情况。术后心肌梗死定义为肌酸激酶MB同工酶值≥100 ng/mL，或Q波型心肌梗死且肌酸激酶MB同工酶值≥70 ng/mL，或术后30天时出现新的Q波型心肌梗死证据。由于接受冠状动脉旁路移植术并伴有瓣膜手术的患者未纳入主要研究人群，因此对218例接受主动脉瓣置换术和冠状动脉旁路移植术联合手术的患者进行了死亡和心肌梗死的单独分析。
在353例随机接受任何瓣膜手术的患者中，培昔利珠单抗治疗组有106例（61%）接受了主动脉瓣置换术和冠状动脉旁路移植术联合手术，而安慰剂组有112例（63%）。139例（64%）患者进行冠状动脉旁路移植术时使用了1根或更多胸廓内动脉移植物，179例（82%）患者使用了1根或更多大隐静脉移植物。术后30天时，培昔利珠单抗组有4例（3.8%）死亡，安慰剂组有11例（9.9%）；术后180天时，活性药物组有6例（5.7%）死亡，安慰剂组有16例（14.4%）（Fisher精确检验，P值分别为0.107和0.043）。两组手术干预后30天的心肌梗死发生率相同，但该研究并非旨在检测这组患者中的差异。
培昔利珠单抗抑制补体激活使218例接受主动脉瓣置换术和冠状动脉旁路移植术联合手术的患者在180天时死亡率降低。有必要进行更多研究以证实培昔利珠单抗在主动脉瓣置换术和冠状动脉旁路移植术联合手术中降低死亡率的作用。
