EFFECTS OF GEMFIBROZIL AND CIPROFIBRATE ON PLASMA-LEVELS OF TISSUE-TYPE PLASMINOGEN-ACTIVATOR, PLASMINOGEN-ACTIVATOR INHIBITOR-1 AND FIBRINOGEN IN HYPERLIPIDEMIC PATIENTS

Evaluation of fibrate treatment in humans has focused primarily on its anti-lipidaemic effects. A potentially favourable haemostasis-modulat ing activity of fibrates has also been recognized but the data are not consistent. We sought to learn more about this variability by examini ng the effects of gemfibrozil and ciprofibrate on plasma levels of tis sue-type plasminogen activator (t-PA), plasminogen activator inhibitor -1 (PAI-1) and fibrinogen in primary hyperlipidaemic patients after si x and twelve weeks of treatment using different assay systems for PAI- 1 and fibrinogen. Although both fibrates effectively lowered triglycer ide and cholesterol levels, no effect on the elevated baseline antigen levels of t-PA and PAI-1 was observed after fibrate treatment. Howeve r, both fibrates influenced plasma fibrinogen levels, albeit in a diff erent way. Fibrinogen antigen levels were elevated by 17.6% (p <0.05) and 24.3% (p <0.001) with gemfibrozil after six and twelve weeks, resp ectively, whereas with ciprofibrate there was no effect. Using a Claus s functional assay with either a mechanical end point or a turbidity-b ased end point, no significant change in fibrinogen levels was seen af ter six weeks of gemfibrozil treatment. However, after twelve weeks, g emfibrozil enhanced functional fibrinogen levels by 7.2% (p <0.05) as, assessed by the Clauss mechanical assay, but decreased functional fib rinogen levels by 12.5% (p <0.0001) when a Clauss assay based on turbi dity was used. After six or twelve weeks of ciprofibrate treatment, fu nctional fibrinogen levels were decreased by 10.1% (p <0.001) and 10.5 % (p <0.0001), respectively on the basis of Clauss mechanical and by 1 4.2% (p <0.001) and 28.2% (p <0.0001), respectively with the Clauss tu rbidimetric assay. A remarkable and consistent finding with both fibra tes was the decrease in functionality of fibrinogen as assessed by the ratio of functional fibrinogen (determined by either of the two Claus s assays) to fibrinogen antigen. Taken together, our results indicate that at least part of the variability in the effects of fibrates on ha emostatic parameters can be explained by intrinsic differences between various fibrates, by differences in treatment period and/or by the di fferent outcomes of various assay systems. Interestingly, the two fibr ates tested both reduced the functionality of fibrinogen.