Théroux P, Grégoire J, Chin C, Pelletier G, de Guise P, Juneau M
Department of Medicine, Montreal Heart Institute and University of Montreal, Quebec, Canada.
J Am Coll Cardiol. 1998 Sep;32(3):620-8. doi: 10.1016/s0735-1097(98)00281-2.
This study was defined as a pilot investigation of the usefulness and safety of intravenous diltiazem as adjunctive therapy to tissue plasminogen activator in acute myocardial infarction, followed by oral therapy for 4 weeks.
Experimental studies have documented that calcium antagonists protect the myocardial cell against the damage caused by coronary artery occlusion and reperfusion, yet no benefits have been conclusively demonstrated in acute myocardial infarction (AMI) in humans.
In this pilot study, 59 patients with an AMI treated with tissue-type plasminogen activator (t-PA) were randomized, double blinded, to intravenous diltiazem or placebo for 48 h, followed by oral therapy for 4 weeks. The primary objective was to detect an effect on indices of regional left ventricular function and perfusion. Patients were also closely monitored for clinical events, coronary artery patency and indices of infarct size and of left ventricular function.
Creatine kinase elevation, Q wave score, global and regional left ventricular function and coronary artery patency at 48 h were not significantly different between the diltiazem and placebo groups. A greater improvement observed in regional perfusion and function with diltiazem was likely explained by initial larger defects. Diltiazem, compared to placebo, reduced the rate of death, reinfarction or recurrent ischemia at 35 days from 41% to 13% (p=0.027) and prevented the need for an urgent intervention. The rate of death or myocardial infarction was reduced by 65% (p=0.15). These benefits could not be explained by differences in baseline characteristics such as age, site and extent of infarction, time of inclusion or concomitant therapy. Heart rate and blood pressure were reduced throughout the study with active diltiazem treatment. Side effects of diltiazem were bradycardia and hypotension that required transient or permanent discontinuation of the study drug in 27% of patients, vs. 17% of patients with placebo.
A protective effect for clinical events related to early postinfarction ischemia and reinfarction was suggested in this study, with diltiazem administered intravenously with t-PA followed by oral therapy for 1 month, with no effect on coronary artery patency and left ventricular function and perfusion.
本研究被定义为一项关于静脉注射地尔硫䓬作为急性心肌梗死中组织型纤溶酶原激活剂辅助治疗的有效性和安全性的初步调查，随后进行为期4周的口服治疗。
实验研究已证明钙拮抗剂可保护心肌细胞免受冠状动脉闭塞和再灌注所造成的损伤，但在人类急性心肌梗死（AMI）中尚未最终证实其益处。
在这项初步研究中，59例接受组织型纤溶酶原激活剂（t-PA）治疗的AMI患者被随机、双盲分为静脉注射地尔硫䓬组或安慰剂组，持续48小时，随后进行为期4周的口服治疗。主要目的是检测对局部左心室功能和灌注指标的影响。还对患者的临床事件、冠状动脉通畅情况以及梗死面积和左心室功能指标进行密切监测。
地尔硫䓬组和安慰剂组在48小时时的肌酸激酶升高、Q波评分、整体和局部左心室功能以及冠状动脉通畅情况无显著差异。地尔硫䓬组观察到的局部灌注和功能改善更大，这可能是由最初较大的缺损所解释。与安慰剂相比，地尔硫䓬将35天时的死亡、再梗死或复发性缺血发生率从41%降至13%（p = 0.027），并避免了紧急干预的需要。死亡或心肌梗死发生率降低了65%（p = 0.15）。这些益处无法通过年龄、梗死部位和范围、纳入时间或伴随治疗等基线特征的差异来解释。在整个研究中，活性地尔硫䓬治疗使心率和血压降低。地尔硫䓬的副作用为心动过缓和低血压，27%的患者需要暂时或永久停用研究药物，而安慰剂组为17%。
本研究提示，在急性心肌梗死后早期，静脉注射地尔硫䓬联合t-PA并随后进行1个月的口服治疗，对与缺血和再梗死相关的临床事件具有保护作用，对冠状动脉通畅情况、左心室功能和灌注无影响。
