Boden W E, Scheldewaert R, Walters E G, Whitehead A, Coltart D J, Santoni J P, Belgrave G, Starkey I R
Boston VA Medical Center, Massachusetts 02130, USA.
Am J Cardiol. 1995 Jun 1;75(16):1120-3. doi: 10.1016/s0002-9149(99)80742-5.
Several pharmacologic forms of adjunctive therapy, designed to enhance the efficacy of thrombolysis following acute myocardial infarction (AMI), are being explored. However, few studies have assessed the use of standard secondary prevention therapies (beta-blockers, angiotensin-converting enzyme inhibitors, magnesium, calcium antagonists, etc.) for antecedent thrombolysis. Although calcium antagonists have not been shown to alter post-AMI mortality, diltiazem has been shown to reduce recurrent nonfatal infarction and myocardial ischemia following non-Q-wave AMI. Because both non-Q-wave AMI and AMI treated with thrombolytic therapy result in early reperfusion and clinical manifestations of "incomplete infarction" (i.e., aborted transmural infarction), we hypothesize that prophylactic administration of diltiazem to AMI patients who receive thrombolysis before other therapies might decrease ischemic complications. We have initiated a multicenter, randomized, placebo-controlled, double-blind, parallel-group comparison of long-acting diltiazem 300 mg/day and aspirin 160 mg/day versus aspirin 160 mg/day alone in up to 920 patients with an uncomplicated first AMI (no heart failure or left ventricular dysfunction) within 36 to 96 hours of receiving thrombolysis. Active enrollment is under way at 46 centers in the United Kingdom, Belgium, The Netherlands, and Denmark. This trial (known as the Incomplete INfarction Trial of European Research Collaborators Evaluating Prognosis Post-Thrombolysis [diltiazem], or INTERCEPT) represents the first long-term, large-scale, prospective study of a calcium antagonist administered post-thrombolysis as adjunctive therapy to AMI patients in which the primary trial objective is to assess the effect of blinded therapy on the 6-month cumulative occurrence of a combined clinical end point (cardiac death, recurrent nonfatal AMI, and medically refractory ischemia).
目前正在探索几种辅助治疗的药理学形式，旨在提高急性心肌梗死（AMI）后溶栓治疗的疗效。然而，很少有研究评估标准二级预防疗法（β受体阻滞剂、血管紧张素转换酶抑制剂、镁、钙拮抗剂等）用于先行溶栓治疗的情况。尽管钙拮抗剂尚未被证明能改变AMI后的死亡率，但地尔硫卓已被证明可减少非Q波AMI后的复发性非致命性梗死和心肌缺血。由于非Q波AMI和接受溶栓治疗的AMI都会导致早期再灌注和“不完全梗死”的临床表现（即透壁梗死未完成），我们假设在其他治疗之前对接受溶栓治疗的AMI患者预防性给予地尔硫卓可能会减少缺血性并发症。我们已启动一项多中心、随机、安慰剂对照、双盲、平行组比较研究，将920例在接受溶栓治疗后36至96小时内发生无并发症首次AMI（无心力衰竭或左心室功能障碍）的患者，分为两组，一组每天服用300毫克长效地尔硫卓和160毫克阿司匹林，另一组仅每天服用160毫克阿司匹林。英国、比利时、荷兰和丹麦的46个中心正在积极招募患者。该试验（称为欧洲研究合作者评估溶栓后预后的不完全梗死试验[diltiazem]，或INTERCEPT）是第一项针对AMI患者溶栓后给予钙拮抗剂作为辅助治疗的长期、大规模、前瞻性研究，其主要试验目标是评估盲法治疗对6个月联合临床终点（心源性死亡、复发性非致命性AMI和药物难治性缺血）累积发生率的影响。
