Becker R C, Charlesworth A, Wilcox R G, Hampton J, Skene A, Gore J M, Topol E J
Thrombosis Research Center, University of Massachusetts Medical School, Worcester.
J Am Coll Cardiol. 1995 Apr;25(5):1063-8. doi: 10.1016/0735-1097(94)00524-t.
This prospective ancillary study was conducted to determine the association between the time from symptom onset to treatment and cardiac rupture in patients with acute myocardial infarction.
There is strong evidence that the time window for thrombolytic therapy should be extended to at least 12 h; however, many clinicians are concerned that late treatment may cause an excessive occurrence of death from cardiac rupture. Because up to 30% of patients with acute myocardial infarction arrive in the hospital > 6 h from symptom onset, resolving this issue is of paramount clinical importance.
A total of 5,711 patients with acute myocardial infarction were randomized to receive intravenous recombinant tissue-type plasminogen activator (rt-PA) (100 mg over 3 h) or matching placebo, within 6 and 24 h from symptom onset. Both groups received immediate oral aspirin, and a majority of patients received intravenous heparin during the initial 48 h.
By 35 days, 177 patients had died, with the cause of death specified as cardiac rupture (53 patients), electromechanical dissociation (42 patients) or asystole (82 patients). An additional 370 patients had died of other causes. In patients treated within 12 h, the proportion of rupture deaths in the group given rt-PA was higher than that observed in those who received placebo, but the difference was not statistically significant. In patients treated after 12 h, there was no evidence of an increased incidence of rupture with rt-PA, and the proportion of deaths due to rupture in this group was lower than that in patients given placebo. However, there was evidence of a difference between rt-PA and placebo with respect to the time that rupture became clinically manifest (treatment by time to death interaction, p = 0.03).
This study provides unequivocal evidence that late treatment (6 to 24 h after symptom onset) with rt-PA is not associated with an increased risk of cardiac rupture. However, for reasons that are unclear, coronary thrombolysis appears to accelerate rupture events, typically to within 24 h of treatment.
开展这项前瞻性辅助研究以确定急性心肌梗死患者从症状出现到治疗的时间与心脏破裂之间的关联。
有强有力的证据表明溶栓治疗的时间窗应延长至至少12小时；然而，许多临床医生担心延迟治疗可能导致心脏破裂死亡的发生率过高。由于高达30%的急性心肌梗死患者在症状出现6小时后才抵达医院，解决这一问题具有至关重要的临床意义。
共有5711例急性心肌梗死患者在症状出现6至24小时内被随机分配接受静脉注射重组组织型纤溶酶原激活剂（rt-PA）（3小时内注射100毫克）或匹配的安慰剂。两组均立即口服阿司匹林，大多数患者在最初48小时内接受静脉注射肝素。
到第35天时，177例患者死亡，死亡原因明确为心脏破裂（53例患者）、心电机械分离（42例患者）或心搏停止（82例患者）。另外370例患者死于其他原因。在12小时内接受治疗的患者中，接受rt-PA治疗组的破裂死亡比例高于接受安慰剂治疗组，但差异无统计学意义。在12小时后接受治疗的患者中，没有证据表明rt-PA会增加破裂发生率，且该组因破裂导致的死亡比例低于接受安慰剂治疗的患者。然而，有证据表明rt-PA与安慰剂在破裂临床显现时间方面存在差异（治疗时间与死亡交互作用，p = 0.03）。
本研究提供了明确的证据，即症状出现后6至24小时使用rt-PA进行延迟治疗与心脏破裂风险增加无关。然而，由于不明原因，冠状动脉溶栓似乎会加速破裂事件，通常在治疗后24小时内发生。
