急性心肌梗死期间冠状动脉内注射亚硝酸盐的随机2期试验
Randomized phase 2 trial of intracoronary nitrite during acute myocardial infarction.
作者信息
Jones Daniel A, Pellaton Cyril, Velmurugan Shanti, Rathod Krishnaraj Sinha, Andiapen Mervyn, Antoniou Sotiris, van Eijl Sven, Webb Andrew J, Westwood Mark A, Parmar Mahesh K, Mathur Anthony, Ahluwalia Amrita
机构信息
From the Barts National Institute for Health Research Cardiovascular Biomedical Research Unit, William Harvey Research Institute, Barts and The London Medical School (D.A.J., S.V., K.S.R., S.A., S.v.E., A.J.W., A.M., A.A.); and Department of Cardiology, London Chest Hospital, Barts Health NHS Trust (D.A.J., C.P., S.V., M.A., M.A.W., A.M.), and MRC Clinical Trials Unit at UCL (M.K.P.), University College London, Aviation House, Kingsway, London, UK.
出版信息
Circ Res. 2015 Jan 30;116(3):437-47. doi: 10.1161/CIRCRESAHA.116.305082. Epub 2014 Dec 15.
RATIONALE
Preclinical evidence demonstrates that inorganic nitrite, after its in situ conversion to nitric oxide, attenuates consequent myocardial reperfusion injury.
OBJECTIVE
We investigated whether intracoronary injection of nitrite during primary percutaneous coronary intervention might improve infarct size in ST-elevated myocardial infarction.
METHODS AND RESULTS
Patients undergoing primary percutaneous coronary intervention (n=80) were randomized to receive intracoronary (10 mL) sodium nitrite (1.8 μmol) or NaCl (placebo) before balloon inflation. The primary end point was infarct size assessed by measuring creatine kinase release. Secondary outcomes included infarct size assessed by troponin T release and by cardiac MRI on day 2. Baseline characteristics were similar between the groups. No evidence of differences in creatine kinase release (P=0.92), troponin T (P=0.85), or cardiac MRI-assessed infarct size (P=0.254) were evident. In contrast, there was an improvement [corrected] in myocardial salvage index (P=0.05) and reduction in [corrected] major adverse cardiac event at 1 year (2.6% versus 15.8%; P=0.04) in the nitrite group. In a 66-patient subgroup with thrombolysis in myocardial infarction ≤1 flow, there was reduced serum creatine kinase (P=0.030) and a 19% reduction in cardiac MRI-determined infarct size (P=0.034) with nitrite. No adverse effects of nitrite were detected.
CONCLUSIONS
In this phase II study, intracoronary nitrite infusion did not alter infarct size, although a trend to improved myocardial salvage index and a significant reduction in major adverse cardiac event was evident. In a subgroup of patients with thrombolysis in myocardial infarction flow ≤1, nitrite reduced infarct size and major adverse cardiac event and improved myocardial salvage index, indicating that a phase III clinical trial assessing intracoronary nitrite administration as an adjunct to percutaneous coronary intervention in ST-elevated myocardial infarction patients is warranted.
CLINICAL TRIAL REGISTRATION URL
http://www.clinicaltrials.gov. Unique identifier: NCT01584453.
原理
临床前证据表明，无机亚硝酸盐原位转化为一氧化氮后，可减轻随后的心肌再灌注损伤。
目的
我们研究了在直接经皮冠状动脉介入治疗期间冠状动脉内注射亚硝酸盐是否可缩小ST段抬高型心肌梗死的梗死面积。
方法与结果
接受直接经皮冠状动脉介入治疗的患者（n = 80）在球囊扩张前被随机分为冠状动脉内注射（10 mL）亚硝酸钠（1.8 μmol）或氯化钠（安慰剂）组。主要终点是通过测量肌酸激酶释放来评估梗死面积。次要结局包括在第2天通过肌钙蛋白T释放和心脏磁共振成像评估的梗死面积。两组间基线特征相似。肌酸激酶释放（P = 0.92）、肌钙蛋白T（P = 0.85）或心脏磁共振成像评估的梗死面积（P = 0.254）均无差异。相比之下，亚硝酸盐组的心肌挽救指数有所改善（校正后P = 0.05），1年时主要不良心脏事件减少（校正后，2.6% 对15.8%；P = 0.04）。在心肌梗死溶栓血流≤1级的66例患者亚组中，亚硝酸盐使血清肌酸激酶降低（P = 0.030），心脏磁共振成像测定的梗死面积减少19%（P = 0.034）。未检测到亚硝酸盐的不良反应。
结论
在这项II期研究中，冠状动脉内输注亚硝酸盐虽未改变梗死面积，但心肌挽救指数有改善趋势，主要不良心脏事件显著减少。在心肌梗死溶栓血流≤1级的患者亚组中，亚硝酸盐可缩小梗死面积、减少主要不良心脏事件并改善心肌挽救指数，表明有必要进行一项III期临床试验，评估冠状动脉内注射亚硝酸盐作为ST段抬高型心肌梗死患者经皮冠状动脉介入治疗辅助手段的效果。
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