Does long-term angiotensin converting enzyme inhibition affect the concentration of tissue-type plasminogen activator plasminogen activator inhibitor-1 in the blood of patients with a previous myocardial infarction

Background 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. Objectives 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. Methods Fifty-six patients with acute myocardial infarction and a wall motion index less than or equal to 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 (AUC(1-12)) from month 1 to month 12. Results 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 AUC(1-12) t-PA antigen [11.67 (3.95-26.45) versus 10.34 ng/ml (3.71-19.02), P=0.19] and AUC(1-12) 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 AUC(1-12) of t-PA antigen in the D 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. Conclusions 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. (C) Rapid Science Publishers ISSN 0954-6928.