Effects of captopril therapy on endogenous fibrinolysis in men with recent, uncomplicated myocardial infarction.
OBJECTIVE
This study investigated the effects of captopril therapy on endogenous fibrinolysis in men with recent, uncomplicated myocardial infarction.


BACKGROUND
Angiotensin-converting enzyme inhibitors reduce the incidence of acute coronary syndromes in patients with mild left ventricular dysfunction after myocardial infarction. Abnormal endogenous fibrinolysis, reflected in increased levels of endogenous tissue-type plasminogen activator (t-PA) antigen and plasminogen activator inhibitor type 1 activity, is associated with an increased risk of myocardial infarction in patients with ischemic heart disease.


METHODS
In a randomized, double-blind crossover study beginning 8 weeks after uncomplicated myocardial infarction, patients received 4 weeks of placebo and 4 weeks of captopril (75 mg daily) therapy. At the end of each treatment period, we measured t-PA antigen and plasminogen activator inhibitor type 1 antigen and activity.


RESULTS
Median values in the 15 patients after placebo and in 12 normal men matched for age and body mass index were, respectively, t-PA antigen 16.0 versus 9.5 ng/ml (p = 0.001), plasminogen activator inhibitor type 1 antigen 17.3 versus 8.6 ng/ml (p = 0.29) and plasminogen activator inhibitor type 1 activity 13.2 versus 6.3 AU/ml (p = 0.04). After 4 weeks of treatment with captopril in the 15 patients, the estimated (95% confidence interval) median reduction in t-PA antigen was 7.3 ng/ml (-4.6 to -10.3 ng/ml, p = 0.001), in plasminogen activator inhibitor type 1 antigen 3.1 ng/ml (+1.5 to -8.4 ng/ml, p = 0.17) and in plasminogen activator inhibitor type 1 activity -2.2 AU/ml (-1.0 to -4.3 AU/ml, p = 0.02).


CONCLUSIONS
Treatment with captopril after uncomplicated myocardial infarction is associated with a significant decrease in elevated levels of t-PA antigen and plasminogen activator inhibitor type 1 activity. This may help to explain the reduction in risk of coronary thrombosis associated with the use of angiotensin-converting enzyme inhibitors.
Wright
R A
RA
Cardiovascular Research Unit, University of Edinburgh, United Kingdom.
Flapan
A D
AD
Alberti
K G
KG
Ludlam
C A
CA
Fox
K A
KA
D002216:Captopril / Q000008:administration & dosage / Q000494:pharmacology*; D003864:Depression, Chemical; D004311:Double-Blind Method; D005342:Fibrinolysis / Q000187:drug effects*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000175:diagnosis / Q000188:drug therapy* / Q000453:epidemiology; D010919:Placebos; D017395:Plasminogen Activator Inhibitor 1 / Q000097:blood; D013223:Statistics as Topic / Q000379:methods; D013997:Time Factors; D010959:Tissue Plasminogen Activator / Q000097:blood / Q000187:drug effects
D010919:Placebos; D017395:Plasminogen Activator Inhibitor 1; D002216:Captopril; D010959:Tissue Plasminogen Activator