Jang Ik-Kyung, Weissman Neil J, Picard Michael H, Zile Michael R, Pettigrew Veronica, Shen Steven, Tatsuno Jun, Hibberd Mark G, Tzivoni Dan, Wackers Frans J Th
Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114, USA.
Am Heart J. 2008 Jan;155(1):113.e1-8. doi: 10.1016/j.ahj.2007.08.020. Epub 2007 Nov 1.
The objective of the study was to test the hypothesis that intracellular calcium modulation by 5-methyl-2-[piperazin-1-yl] benzene sulfonic acid monohydrate (MCC-135 [Caldaret]; Mitsubishi Pharma Corporation, Osaka, Japan) would preserve left ventricular function and reduce infarct size in patients undergoing primary percutaneous coronary intervention (PCI) for ST-elevation myocardial infarction (STEMI).
Calcium overload inside myocytes during ischemia and reperfusion not only affects myocardial function but also may be related to myocyte necrosis. MCC-135 is the first in a new class of agents that modulate intracellular calcium overload.
Patients with acute STEMI undergoing primary PCI were randomized into placebo, low-dose, and high-dose MCC-135 groups. The predefined target population was those with anterior myocardial infarction and pre-PCI TIMI grade flow 0 or 1. Left ventricular ejection fraction (LVEF) on Day 5 was the primary end point. Secondary end points included infarct size measured by single photon emission computed tomography and by serum cardiac markers. Patients were followed up to 30 days for clinical outcome.
Among 500 patients enrolled, 141 qualified as the target population. In this target population, there was no difference in the LVEF between 3 groups (placebo: 47.0% +/- 1.7% [mean +/- SEM], the low dose: 47.4% +/- 1.7%, the high dose: 45.1% +/- 2.0%). The infarct size on day 5 was not significantly different between the groups. The composite clinical outcome occurred in 25.5% in the placebo group, in 19.2% in the low-dose group, and in 34.2% in the high-dose group during a 30-day follow-up period (P = nonsignificant). MCC-135 appeared to be safe and well tolerated.
There were no significant benefits of MCC-135 on preservation of LVEF and reduction of infarct size on day 5 in patients with STEMI undergoing primary PCI.
本研究的目的是检验以下假设：5-甲基-2-[哌嗪-1-基]苯磺酸一水合物（MCC-135 [Caldaret]；日本大阪三菱制药公司）对细胞内钙的调节作用可在接受ST段抬高型心肌梗死（STEMI）直接经皮冠状动脉介入治疗（PCI）的患者中保留左心室功能并缩小梗死面积。
缺血和再灌注期间心肌细胞内的钙超载不仅会影响心肌功能，还可能与心肌细胞坏死有关。MCC-135是一类新型细胞内钙超载调节剂中的首个药物。
将接受直接PCI的急性STEMI患者随机分为安慰剂组、低剂量MCC-135组和高剂量MCC-135组。预先定义的目标人群为前壁心肌梗死且PCI术前心肌梗死溶栓治疗（TIMI）血流分级为0级或1级的患者。第5天的左心室射血分数（LVEF）为主要终点。次要终点包括通过单光子发射计算机断层扫描和血清心脏标志物测量的梗死面积。对患者进行30天的随访以观察临床结局。
在纳入的500例患者中，141例符合目标人群标准。在该目标人群中，三组之间的LVEF无差异（安慰剂组：47.0%±1.7% [平均值±标准误]，低剂量组：47.4%±1.7%，高剂量组：45.1%±2.0%）。各组第5天的梗死面积无显著差异。在30天的随访期内，安慰剂组的复合临床结局发生率为25.5%，低剂量组为19.2%，高剂量组为34.2%（P =无显著性差异）。MCC-135似乎安全且耐受性良好。
对于接受直接PCI的STEMI患者，MCC-135在第5天保留LVEF和缩小梗死面积方面无显著益处。
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