早期使用 N-乙酰半胱氨酸联合硝酸盐治疗对行直接经皮冠状动脉介入治疗的 ST 段抬高型心肌梗死患者的心肌梗死面积的影响（NACIAM 试验[急性心肌梗死后的 N-乙酰半胱氨酸]）。
Early Use of N-acetylcysteine With Nitrate Therapy in Patients Undergoing Primary Percutaneous Coronary Intervention for ST-Segment-Elevation Myocardial Infarction Reduces Myocardial Infarct Size (the NACIAM Trial [N-acetylcysteine in Acute Myocardial Infarction]).
机构信息
From Discipline of Medicine, University of Adelaide, Australia (S.P., R.T., B.R., N.E.K.P., Y.T.D., G.M., C.Z., M.A., J.D.H., J.F.B); Basil Hetzel Institute for Translational Health Research, Adelaide, Australia (S.P., R.T., B.R., N.E.K.P., I.S., T.H., A.H., C.Z., J.D.H., J.F.B); Central Adelaide Local Health Network, Australia (S.P., R.T., B.R., N.E.K.P., Y.D., G.M., I.S., T.H., A.H., C.Z., J.D.H., J.F.B); Northern Adelaide Local Health Network, Australia (G.M., C.Z., M.A., J.F.B.); Southern Adelaide Local Health Network, Australia (S.G., J.S.); Discipline of Medicine, Flinders University, Adelaide, Australia (S.G., J.S.); and South Australian Health and Medical Research Institute, Adelaide, Australia (J.S.).
出版信息
Circulation. 2017 Sep 5;136(10):894-903. doi: 10.1161/CIRCULATIONAHA.117.027575. Epub 2017 Jun 20.
BACKGROUND
Contemporary ST-segment-elevation myocardial infarction management involves primary percutaneous coronary intervention, with ongoing studies focusing on infarct size reduction using ancillary therapies. N-acetylcysteine (NAC) is an antioxidant with reactive oxygen species scavenging properties that also potentiates the effects of nitroglycerin and thus represents a potentially beneficial ancillary therapy in primary percutaneous coronary intervention. The NACIAM trial (N-acetylcysteine in Acute Myocardial Infarction) examined the effects of NAC on infarct size in patients with ST-segment-elevation myocardial infarction undergoing percutaneous coronary intervention.
METHODS
This randomized, double-blind, placebo-controlled, multicenter study evaluated the effects of intravenous high-dose NAC (29 g over 2 days) with background low-dose nitroglycerin (7.2 mg over 2 days) on early cardiac magnetic resonance imaging-assessed infarct size. Secondary end points included cardiac magnetic resonance-determined myocardial salvage and creatine kinase kinetics.
RESULTS
Of 112 randomized patients with ST-segment-elevation myocardial infarction, 75 (37 in NAC group, 38 in placebo group) underwent early cardiac magnetic resonance imaging. Median duration of ischemia pretreatment was 2.4 hours. With background nitroglycerin infusion administered to all patients, those randomized to NAC exhibited an absolute 5.5% reduction in cardiac magnetic resonance-assessed infarct size relative to placebo (median, 11.0%; [interquartile range 4.1, 16.3] versus 16.5%; [interquartile range 10.7, 24.2]; =0.02). Myocardial salvage was approximately doubled in the NAC group (60%; interquartile range, 37-79) compared with placebo (27%; interquartile range, 14-42; <0.01) and median creatine kinase areas under the curve were 22 000 and 38 000 IU·h in the NAC and placebo groups, respectively (=0.08).
CONCLUSIONS
High-dose intravenous NAC administered with low-dose intravenous nitroglycerin is associated with reduced infarct size in patients with ST-segment-elevation myocardial infarction undergoing percutaneous coronary intervention. A larger study is required to assess the impact of this therapy on clinical cardiac outcomes.
CLINICAL TRIAL REGISTRATION
Australian New Zealand Clinical Trials Registry. URL: http://www.anzctr.org.au/. Unique identifier: 12610000280000.
背景
当代 ST 段抬高型心肌梗死的治疗包括经皮冠状动脉介入治疗，目前的研究重点是使用辅助治疗来减少梗死面积。N-乙酰半胱氨酸（NAC）是一种具有活性氧清除特性的抗氧化剂，还能增强硝酸甘油的作用，因此在经皮冠状动脉介入治疗中是一种潜在有益的辅助治疗药物。NACIAM 试验（N-乙酰半胱氨酸在急性心肌梗死中的应用）研究了 NAC 对行经皮冠状动脉介入治疗的 ST 段抬高型心肌梗死患者梗死面积的影响。
方法
这是一项随机、双盲、安慰剂对照、多中心研究，评估了静脉内大剂量 NAC（2 天内 29 克）联合背景低剂量硝酸甘油（2 天内 7.2 毫克）对早期心脏磁共振成像评估的梗死面积的影响。次要终点包括心脏磁共振确定的心肌挽救和肌酸激酶动力学。
结果
112 例随机 ST 段抬高型心肌梗死患者中，75 例（NAC 组 37 例，安慰剂组 38 例）接受了早期心脏磁共振成像。预处理缺血时间的中位数为 2.4 小时。所有患者均给予背景硝酸甘油输注，与安慰剂组相比，随机给予 NAC 的患者心脏磁共振评估的梗死面积绝对减少 5.5%（中位数，11.0%；[四分位间距 4.1%，16.3%] vs 16.5%；[四分位间距 10.7%，24.2%]；=0.02）。NAC 组的心肌挽救率约为安慰剂组的两倍（60%；四分位间距，37%79%）（27%；四分位间距，14%42%；<0.01），NAC 和安慰剂组的肌酸激酶曲线下面积中位数分别为 22000 和 38000 IU·h（=0.08）。
结论
在接受经皮冠状动脉介入治疗的 ST 段抬高型心肌梗死患者中，静脉内大剂量 NAC 联合小剂量静脉内硝酸甘油治疗与梗死面积缩小相关。需要更大规模的研究来评估这种治疗方法对临床心脏结局的影响。
临床试验注册
澳大利亚和新西兰临床试验注册中心。网址：http://www.anzctr.org.au/。独特标识符：12610000280000。
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