The decrease of plasminogen activator inhibitor after normalization of triglycerides during treatment with fibrates

Abstract

Impaired fibrinolysis due to a high level of plasminogen activator inhibitor-1 (PAI-1) has been reported in patients with hypertriglyceridemia. We studied the fibrinolytic effects of the hypolipemic drugs gemfibrozil and fenofibrate that mainly affect triglyceride-rich lipoproteins in 27 patients with severe hypertriglyceridemia (Fredrickson's type IV and V). After a wash-out period of 4 weeks the patients were ramdomly cross-treated with gemfibrozil (600 mg b.i.d.) and fenofibrate (250 mg daily), each time for 6 weeks. Tissue-type plasminogen activator (t-PA) antigen, t-PA activity, PAI-1 antigen, PAI activity and serum lipids were measured before and after the 6 weeks of either treatment. Basal levels of PAI-1 antigen and activity were very high and did not change after any treatment in the whole group of patients, while the mean triglyceride level decreased by 49% after gemfibrozil and by 39% after fenofibrate. However, a significant decrease in PAI-1 antigen was observed in a subgroup of 9 patients treated with gemfibrozil, in whom triglycerides decreased to or below 2.8 mmol/1. In all patients t-PA antigen decreased significantly after treatment with either drug, while t-PA activity decreased only after fenofibrate. It was concluded that almost normal values of triglycerides should be achieved during treatment with fibrates in order to decrease high PAI-1 antigen and activity levels. On the other hand, the decrease of t-PA antigen during fibrate treatment seems not to be associated with the degree of triglyceride-lowering effect of these drugs.