Fibrinolytic variables and cardiovascular prognosis in patients with stable angina pectoris treated with verapamil or metoprolol. Results from the Angina Prognosis study in Stockholm

BACKGROUND: Disturbed fibrinolytic function may influence the progression of coronary atherosclerosis and contribute to thrombotic cardiovascular (CV) events. METHODS AND RESULTS: In the Angina Prognosis Study in Stockholm (APSIS), patients with stable angina pectoris were studied prospectively during double blind treatment with metoprolol or verapamil. Various measures of fibrinolytic function were studied in 631 (of 809) patients. During a median follow up time of 3.2 years (2132 patient years), 32 patients suffered a CV death, 21 had a nonfatal myocardial infarction (MI), and 77 underwent revascularization. Plasma levels of tissue plasminogen activator (TPA) activity and antigen (ag), plasminogen activator inhibitor (PAI 1) activity at test, and TPA responses to exercise were determined at baseline and after 1 month's treatment and were related to subsequent fatal and nonfatal CV events. Univariate Cox regression analysis revealed that elevated levels of TPA ag at rest (P < .05), high PAI 1 activity (P < .05), and low TPA ag responses to exercise (P < .05) were associated with increased risk of subsequent CV death. After adjustment for baseline risk factors, TPA ag independently predicted CV death or MI. In addition, PAI 1 activity independently predicted CV death or MI in male patients. Verapamil treatment was associated with a 10% decrease of TPA ag levels and metoprolol treatment with a 2% increase (P < .001 for treatment difference). CONCLUSIONS: Plasma TPA ag levels at rest, and among male patients PAI 1 activity as well, independently predict subsequent CV death or MI in patients with stable angina pectoris.