Pedersen O D, Gram J, Jeunemaitre X, Billaud E, Jespersen J
Department of Internal Medicine, Ribe County Hospital in Esbjerg, Denmark.
Coron Artery Dis. 1997 May;8(5):283-91. doi: 10.1097/00019501-199705000-00005.
Large-scale studies have indicated that treatment with angiotensin converting enzyme (ACE) inhibitors reduces the incidence of myocardial infarction and unstable angina pectoris among patients with recent myocardial infarction and moderate left ventricular dysfunction. An improved endogenous fibrinolysis might be responsible for this effect.
To investigate the effect of trandolapril on the endogenous tissue-type plasminogen activator (t-PA) in patients with a recent myocardial infarction and moderate left ventricular dysfunction.
Fifty-six patients with acute myocardial infarction and a wall motion index < or = 1.2 were allocated randomly either to administration of trandolapril or to placebo. When possible, the study drug dose was increased gradually to 4 mg trandolapril or a corresponding amount of placebo during the first month after randomization. Blood samples for determination of the variables of the fibrinolytic system, ACE activity and ACE genotype were collected prior to randomization and during out-patient visits in months 1, 3, 6, 9 and 12. After the subject had fasted overnight, blood samples were collected in the morning (0800-1000 h) after the subject had rested supine for at least 15 min, from a venous cannula inserted into the forearm. The effect of trandolapril on the fibrinolytic variables was evaluated by calculating the area under the curve (AUC1-12) from month 1 to month 12.
The trandolapril group and the placebo group were similar with respect to baseline clinical characteristics, baseline fibrinolytic variables and baseline plasma ACE activity. The trandolapril group did not differ significantly from the placebo group with respect to AUC1-12 t-PA antigen [11.67 (3.95-26.45) versus 10.34 ng/ml (3.71-19.62), P = 0.19] and AUC1-12 plasminogen activator inhibitor type-1 (PAI-1) antigen [27.57 (8.38-89.49) versus 24.40 ng/ml (7.94-90.62), P = 0.92]. A significant and clear trend in variation with time of t-PA antigen was observed for the trandolapril group, but not for the placebo group. The fibrinolytic variables were similar at baseline for the different ACE genotype insertion (I) and deletion (D) groups (II, ID and DD). Trandolapril treatment was associated with a significant (P < 0.04) increase in the AUC1-12 of t-PA antigen in the ID group compared with that of the placebo-treated ID group, whereas PAI-1 antigen concentration did not differ between the groups. Trandolapril treatment was not associated with any significant change in the fibrinolytic variables for the other genotype groups.
Chronic ACE-inhibitor treatment with trandolapril was not associated with any significant difference in the blood concentrations of t-PA and PAI-1 compared with placebo. The suggested specific interaction between ACE inhibition and the increase in t-PA in patients with ACE genotype ID will require further confirmation.
大规模研究表明，使用血管紧张素转换酶（ACE）抑制剂进行治疗可降低近期发生心肌梗死且伴有中度左心室功能不全患者的心肌梗死和不稳定型心绞痛的发生率。内源性纤溶功能的改善可能是造成这种效果的原因。
研究群多普利对近期发生心肌梗死且伴有中度左心室功能不全患者内源性组织型纤溶酶原激活物（t-PA）的影响。
56例急性心肌梗死且室壁运动指数≤1.2的患者被随机分为群多普利治疗组或安慰剂组。在随机分组后的第一个月内，研究药物剂量尽可能逐渐增加至群多普利4mg或相应剂量的安慰剂。在随机分组前以及第1、3、6、9和12个月门诊随访期间采集血样，以测定纤溶系统变量、ACE活性和ACE基因型。受试者过夜禁食后，于早晨（08:00 - 10:00时）在其仰卧休息至少15分钟后，从前臂插入的静脉套管采集血样。通过计算第1个月至第12个月的曲线下面积（AUC1 - 12）来评估群多普利对纤溶变量的影响。
群多普利组和安慰剂组在基线临床特征、基线纤溶变量和基线血浆ACE活性方面相似。群多普利组与安慰剂组在AUC1 - 12 t-PA抗原[11.67（3.95 - 26.45）对10.34ng/ml（3.71 - 19.62），P = 0.19]和AUC1 - 12纤溶酶原激活物抑制剂1型（PAI-1）抗原[27.57（8.38 - 89.49）对24.40ng/ml（7.94 - 90.62），P = 0.92]方面无显著差异。群多普利组观察到t-PA抗原随时间变化有显著且明显的趋势，而安慰剂组未观察到。不同ACE基因型插入（I）和缺失（D）组（II、ID和DD）在基线时纤溶变量相似。与安慰剂治疗的ID组相比，群多普利治疗使ID组的AUC1 - 12 t-PA抗原显著增加（P < 0.04），而两组间PAI-1抗原浓度无差异。群多普利治疗对其他基因型组的纤溶变量无显著影响。
与安慰剂相比，长期使用群多普利进行ACE抑制剂治疗在t-PA和PAI-1血药浓度方面无显著差异。ACE基因型为ID的患者中ACE抑制与t-PA增加之间的特定相互作用有待进一步证实。
