EFFECTS OF RAMIPRIL ON PLASMA FIBRINOLYTIC BALANCE IN PATIENTS WITH ACUTE ANTERIOR MYOCARDIAL-INFARCTION

Background The long-term administration of ACE inhibitors to selected patients with left ventricular dysfunction appears to reduce the incid ence of recurrent myocardial infarction (MI) and unstable angina pecto ris. The mechanisms responsible for the reduction in ischemic events a re unknown, but likely candidates include effects on the atherosclerot ic process, thrombosis, and/or vascular tone. Methods and Results The effects of ACE inhibitor therapy with ramipril on plasma fibrinolytic variables were assessed in 120 subjects participating in the Healing a nd Early Afterload Reduction Therapy (HEART) study, a double-blind, pl acebo-controlled trial of acute anterior MI patients who were randomly assigned within 24 hours of the onset of symptoms to receive low-dose ramipril (0.625 mg daily), full-dose ramipril (1.25 mg titrated to 10 mg/d), or placebo for 14 days. Plasma levels of plasminogen activator inhibitor-1 (PAI-1) activity and PAI-I antigen and tissue plasminogen activator (TPA) antigen were measured before randomization and on day 14. Clinical characteristics of the three study groups were similar, as were the prerandomization plasma levels of PAI-1 antigen, PAI-1 act ivity, and TPA antigen. Compared with the placebo group, PAI-I antigen levels were 44% lower (P=.004) at day 14 in the ramipril-treated pati ents, and PAI-1 activity levels were 22% lower (P=.02). In contrast, p lasma TPA levels were not significantly different between the placebo- treated and ramipril-treated groups. Conclusions Treatment with ramipr il has a significant impact on plasma fibrinolytic variables during th e recovery phase after acute MI. The renin-angiotensin system appears to play an important role in the regulation of vascular fibrinolysis, and interruption of this regulatory pathway may contribute to the clin ical benefits of ACE inhibitors.