Tardif Jean-Claude, Carrier Michel, Kandzari David E, Emery Robert, Cote Robert, Heinonen Therese, Zettler Marjorie, Hasselblad Vic, Guertin Marie-Claude, Harrington Robert A
Montreal Heart Institute, Montreal, Canada.
J Thorac Cardiovasc Surg. 2007 Jun;133(6):1604-11. doi: 10.1016/j.jtcvs.2007.01.049.
Coronary artery bypass graft surgery remains associated with significant postoperative cardiovascular morbidity and mortality in high-risk patients. MC-1 (pyridoxal-5'-phosphate monohydrate) inhibits purinergic receptors and intracellular influx of Ca2+, thereby reducing cellular injury during experimental ischemia and reperfusion. The MEND-CABG trial tested the hypothesis that MC-1 reduces cardiovascular morbidity and mortality after coronary artery bypass graft.
In a phase 2, double-blinded, placebo-controlled study, 901 patients scheduled for coronary artery bypass graft surgery with cardiopulmonary bypass and at high risk for subsequent cardiac or neurologic complications were randomly assigned to receive oral MC-1 (250 mg or 750 mg/d once daily) or placebo beginning 3 to 10 hours prior to surgery and continued to postoperative day 30.
At 30 days, MC-1 250 mg (compared with placebo) reduced the composite of death, nonfatal cerebral infarction, and nonfatal myocardial infarction by 14.0% (P = .3124) with peak creatinine kinase-myocardial band > or =50 ng/mL (prespecified primary end point); 32.3% (P = .0349) with peak creatinine kinase-myocardial band > or =70 ng/mL; and 37.2% (P = .0283) with peak creatinine kinase-myocardial band > or =100 ng/mL. Myocardial infarctions with peak creatinine kinase-myocardial band> or =100 ng/mL were reduced by 47.2% in the MC-1 250-mg group versus placebo (P = .0083). Greater efficacy was demonstrated with 250 mg than with the 750-mg dose of MC-1.
In high-risk patients undergoing coronary artery bypass graft, treatment with MC-1 did not significantly affect the prespecified primary end point but was associated with a significant reduction in perioperative myocardial infarction with creatinine kinase-myocardial band > or =100 ng/mL. A larger, well-powered trial is needed to evaluate the cardioprotective effects of MC-1.
在高危患者中，冠状动脉旁路移植术术后仍存在显著的心血管发病率和死亡率。MC - 1（一水合吡哆醛 - 5'-磷酸）可抑制嘌呤能受体和细胞内钙离子内流，从而减少实验性缺血和再灌注期间的细胞损伤。MEND - CABG试验检验了MC - 1可降低冠状动脉旁路移植术后心血管发病率和死亡率这一假设。
在一项2期、双盲、安慰剂对照研究中，901例计划接受冠状动脉旁路移植术并使用体外循环且随后发生心脏或神经并发症风险较高的患者，被随机分配在手术前3至10小时开始口服MC - 1（250毫克或750毫克/天，每日一次）或安慰剂，并持续至术后第30天。
在30天时，与安慰剂相比，250毫克MC - 1使死亡、非致命性脑梗死和非致命性心肌梗死的复合终点降低了14.0%（P = 0.3124），肌酸激酶 - 心肌型同工酶峰值>或 = 50纳克/毫升（预先设定的主要终点）；肌酸激酶 - 心肌型同工酶峰值>或 = 70纳克/毫升时降低了32.3%（P = 0.0349）；肌酸激酶 - 心肌型同工酶峰值>或 = 100纳克/毫升时降低了37.2%（P = 0.0283）。与安慰剂相比，250毫克MC - 1组中肌酸激酶 - 心肌型同工酶峰值>或 = 100纳克/毫升的心肌梗死减少了47.2%（P = 0.0083）。250毫克剂量的MC - 1比750毫克剂量显示出更大的疗效。
在接受冠状动脉旁路移植术的高危患者中，MC - 1治疗对预先设定的主要终点没有显著影响，但与肌酸激酶 - 心肌型同工酶峰值>或 = 100纳克/毫升的围手术期心肌梗死显著减少有关。需要进行一项规模更大、效能充足的试验来评估MC - 1的心脏保护作用。
