Wagner Andreas, Herkner Harald, Schreiber Wolfgang, Bur Andreas, Woisetschläger Christian, Stix Günther, Laggner Anton N, Hirschl Michael M
Department of Emergency Medicine, General Hospital, University of Vienna, Austria.
Thromb Haemost. 2002 Aug;88(2):180-5.
In a placebo-controlled, double-blinded, randomized study we evaluated the effect of ramipril prior to thrombolysis on the course of PAI-1 plasma levels and on the frequency of postinfarct ischemic events in patients with acute myocardial infarction. Fifty-one out of 99 patients received 2.5 mg ramipril orally prior to thrombolysis and 12 h later. The blood samples for determination of PAI-1 plasma levels were collected on admission and 2, 4, 8, 12 and 24 h after thrombolysis. Postinfarct ischemic events were registered until coronary angiography was performed and defined as recurrent chest pain and/or evidence of ischemic signs on the ECG (ST-depression or ST-segment elevation of 1 mm in one or more inferior or anterior leads). Coronary angiography was performed within 7 days after the onset of myocardial infarction. Patients were classified into two groups: those without reperfusion of the infarct-related artery (TIMI grade 0 or 1) and those with reperfusion of the infarct-related artery (TIMI grade 2.3). On admission, PAI-1 plasma levels were similar in both groups (ramipril: 47.1 [4.8] ng/ml; placebo: 49.1 [4.8] ng/ml). The PAI-1AUC was 77.2 [6.7] ng/ml/h in the ramipril group and 95.4 [6.2] ng/ml/h in the placebo group (p = 0.013). Significant differences between groups were observed at 4, 8 and 12 h after thrombolysis (4 h: 85.5 (11.3) vs. 116 (12.3) ng/ml, p < 0.01; 8 h: 79.1 (11.2) vs. 100.9 (9.3) ng/ml, p < 0.01; 12 hrs: 71.3 (9.5) vs. 87.4 (7.7) ng/ml, p < 0.05). The relative frequency of postinfarct ischemic events was significantly lower in the ramipril group (2.5% versus 7.1%, p = 0.001). Additionally, we observed a significant higher rate of TIMI grade 2 and 3 of the infarct-related artery in patients receiving oral ramipril compared to the placebo group (73% versus 54%; p = 0.035). Our study demonstrates a favorable effect of ramipril on the fibrinolytic system after thrombolysis associated with a lower rate of postinfarct ischemic events within the first days after myocardial infarction. Therefore, the application of ramipril prior to thrombolysis appears to be a reasonable concomitant treatment which may reduce early infarct-related complications.
在一项安慰剂对照、双盲、随机研究中，我们评估了在溶栓治疗前给予雷米普利对急性心肌梗死患者血浆纤溶酶原激活物抑制剂-1（PAI-1）水平变化过程以及梗死后缺血事件发生率的影响。99例患者中有51例在溶栓治疗前及12小时后口服2.5毫克雷米普利。用于测定PAI-1血浆水平的血样在入院时以及溶栓后2、4、8、12和24小时采集。记录梗死后缺血事件直至进行冠状动脉造影，并将其定义为复发性胸痛和/或心电图上有缺血迹象（一个或多个下壁或前壁导联ST段压低或ST段抬高1毫米）。在心肌梗死发作后7天内进行冠状动脉造影。患者分为两组：梗死相关动脉未再灌注的患者（TIMI分级0或1）和梗死相关动脉再灌注的患者（TIMI分级2、3）。入院时，两组患者的PAI-1血浆水平相似（雷米普利组：47.1[4.8]纳克/毫升；安慰剂组：49.1[4.8]纳克/毫升）。雷米普利组的PAI-1曲线下面积（AUC）为77.2[6.7]纳克/毫升/小时，安慰剂组为95.4[6.2]纳克/毫升/小时（p = 0.013）。溶栓后4、8和12小时观察到两组之间存在显著差异（4小时：85.5（11.3）对116（12.3）纳克/毫升，p < 0.01；8小时：79.1（11.2）对100.9（9.3）纳克/毫升，p < 0.01；12小时：71.3（9.5）对87.4（7.7）纳克/毫升，p < 0.05）。雷米普利组梗死后缺血事件的相对发生率显著较低（2.5%对7.1%，p = 0.001）。此外，与安慰剂组相比，接受口服雷米普利的患者梗死相关动脉TIMI分级2和3的发生率显著更高（73%对54%；p = 0.035）。我们的研究表明，雷米普利对溶栓后的纤溶系统有有益作用，与心肌梗死后头几天较低的梗死后缺血事件发生率相关。因此，在溶栓治疗前应用雷米普利似乎是一种合理的联合治疗方法，可能会减少早期梗死相关并发症。
