研究人员在美国心脏病学会第53届科学年会上宣布，抑制钙超载和增加肌浆网钙摄入的新药calderet总的来说没达到人们的预期目标，但它可能用于ST段抬高的心肌梗塞病人，其中前壁梗塞的病人在用它治疗后，心功能的所有标志物均改善。

第一作者、以色列耶路撒冷Shaare Zedek医疗中心的替罗尼（Dan Tzinoni）提交了CAlderet IV期试验结果。研究者从5个国家招募了387名ST段抬高的心肌梗塞（STEMI）病人，他们30天内的总死亡率为2.3%。所有病人都进行了冠状动脉介入治疗（PCI）。为检查calderet作为PCI的辅助治疗是否有效，病人被随机分为小剂量或大剂量calderet组（先45分钟快速输液，然后慢输48小时），或安慰剂组。主要终点是7天时单光子发射计算机断层显象上的梗塞区大小，次要终点是心功能的测量。

替罗尼告诉与会者，尽管大剂量calderet组的病人梗塞区有更小的倾向，但三组之间无显著差异。他着重报告了一小组急性心肌梗塞的病人：这组病人的梗塞区较小（无显著性），但他们中接受大剂量calderet的在7天、30天时的左心室射血分数明显更好，而且前壁梗塞的病人所有心脏病标志物显著下降，而这种病人的死亡率和发病率通常最高。

负责主持本部分会议的是罗德岛医院的威廉姆斯（David O. Williams）。他告诉Medscape的记者，这些结果“听起来非常有希望”，但它只是一项早期研究。他对使用抑制钙超载的药物来治疗心肌梗塞很有兴趣，“在这方面我们还没有尝试过。Calderet很有希望”。

Novel Drug May Reduce Anterior Wall Infarct Mortality

March 8, 2004 (New Orleans) — A novel compound that inhibits calcium overload and increases calcium uptake in the sarcoplasmic reticulum fell short of expectations overall, but calderet showed promise in a subset of patients with ST-segment elevation myocardial infarction (MI). Patients with anterior wall infarcts showed improvement in all markers of cardiac function after treatment, investigators announced here.

Results of the IV CAlderet [MCC-135] in Patients with ST Elevation Myocardial Infarction Undergoing Primary PCI (CASTEMI) study were announced Sunday during a late-breaking clinical trials session at the American College of Cardiology 53rd annual scientific session by lead investigator Dan Tzinoni, MD, from Shaare Zedek Medical Center in Jerusalem, Israel.

The CASTEMI investigators enrolled 387 patients with ST-segment elevation MI (STEMI) and TIMI flow 0/1 recruited from medical centers in five countries. Total mortality during the 30-day study period was 2.3%.

All patients in the study underwent primary coronary intervention (PCI). To determine if calderet was effective as adjunctive therapy with PCI, the investigators randomized patients to low-dose (57.5 mg) or high-dose (172.5 mg) therapy or placebo, administered as a 45-minute rapid infusion followed by a 48-hour slow infusion. Primary end point was infarct size seen on single-photon emission computed tomography at seven days. Secondary end points were measures of cardiac function.

There were no significant differences in infarct size between either of the two doses of calderet or placebo, Dr. Tzivoni told meeting attendees, although there was a trend toward decreased infarct size in patients receiving high-dose therapy.

Dr. Tzivoni focused his presentation on the results observed in the subset of patients with acute MI. In this subgroup, infarct size was slightly but not statistically significantly reduced. However, global left ventricular ejection fraction was significantly better at seven and at 30 days in the high-dose group, and there was a significant decrease in all cardiac markers in patients with anterior infarcts, Dr. Tzivoni said. He pointed out that these patients have the highest morbidity and mortality after MI.

David O. Williams, MD, from Rhode Island Hospital in Providence, moderated the late-breaking clinical trials session during which the CASTEMI results were presented. He told Medscape that the results "sound very promising," but he cautioned that CASTEMI was a very small study.

Dr. Williams said he is intrigued by the use of the calcium overload inhibitor in the setting of MI. "We haven't tried anything toward that end, using that mechanism of action. [Calderet] is a promising agent and it would be absolutely complementary to any other treatment. It doesn't get in the way of anything else, it wouldn't prevent any other approaches."

Dr. Tzivoni said that higher doses of calderet will continue to be investigated in the larger EVOLVE trial.

ACC 53rd Annual Scientific Session: Late-Breaking Clinical Trials — Session 25: Novel Therapies for Acute Myocardial Infarction. Presented March 7, 2004.