The estimated effects of fibrate therapy on plasma concentration and activity of PAI-1 were independent of treatment duration and changes in plasma triglyceride levels in the meta-regression analysis .
This meta- analysis of RCTs suggested that fibrate therapy does not reduce plasma concentration or activity of PAI-I. The putative benefits of fibrate therapy in patients with cardiovascular disease appear to be exerted via mechanisms independent of effects on PAI-1
OBJECTIVE The aim of this systematic review was to perform a meta- analysis of r and omized controlled trials ( RCTs ) examining the efficacy of fibrate therapy in reducing plasma concentration or activity of plasminogen activator inhibitor 1 ( PAI-1 ) .
Effects of two different fibric acid derivatives on lipoproteins, cholesteryl ester transfer, fibrinogen, plasminogen activator inhibitor and paraoxonase activity in type IIb hyperlipoproteinaemia.
We have investigated the effects of two fibric acid derivatives , bezafibrate mono ( 400 mg daily ) and gemfibrozil ( 600 mg b.d . ) , in 29 patients with type IIb hyperlipoproteinaemia . All patients received placebo and each drug for 8 weeks in r and omised order in a double-blind , cross-over study design ed to evaluate any different effects of the drugs on serum lipoproteins , cholesteryl ester transfer protein ( CETP ) , cholesteryl ester transfer activity ( CETA ) , plasma fibrinogen , plasminogen activator inhibitor-I ( PAI-1 ) or paraoxonase . Serum cholesterol decreased ( P < 0.05 ) with gemfibrozil , but the effect of bezafibrate on serum cholesterol did not achieve statistical significance ( placebo 8.34 + /- 1.05 ( mean + /- S.D. ) , gemfibrozil 7.70 + /- 1.23 and bezafibrate 7.8 + /- 1.37 mmol/l ) . Both drugs decreased the serum triglyceride concentration ( both P < 0.001 ) ( placebo 4.39 ( 3.13 - 5.75 ) ( median ( interquartile range ) ) , bezafibrate 2.26 ( 1.89 - 3.89 ) and gemfibrozil 2.00 ( 1.30 - 3.30 ) mmol/l ) and very low density lipoprotein ( VLDL ) cholesterol ( both P < 0.001 ) ( placebo 1.18 ( 0.74 - 2.30 ) , bezafibrate 0.59 ( 0.34 - 0.85 ) and gemfibrozil 0.48 ( 0.34 - 0.68 ) mmol/l ) . Discontinuous gradient ultracentrifugation ( DGU ) revealed that Sf 60 - 400 ( large VLDL ) decreased by more than 50 % and Sf 20 - 60 ( small VLDL ) by more than 30 % with each of the drugs ( both P < 0.001 ) , neither of which affected the composition of these lipoproteins . Gemfibrozil decreased the concentration of Sf 12 - 20 lipoprotein ( intermediate density lipoprotein ; IDL ) by 23 % ( P < 0.01 ) , whereas the effect of bezafibrate on this lipoprotein did not achieve statistical significance . Neither drug altered the concentration of apolipoprotein B or of total Sf 0 - 12 lipoproteins ( low density lipoprotein , ( LDL ) ) . Both , however , significantly increased the quantity of free cholesterol in Sf 0 - 12 lipoproteins ( P < 0.05 ) . Overall the concentration of triglycerides decreased significantly in all lipoproteins isolated by DGU ( Sf 0 - 12 , Sf 12 - 20 , Sf 20 - 60 , Sf 60 - 400 ) on gemfibrozil treatment , but only in Sf 20 - 60 and Sf 60 - 400 on bezafibrate ( all P < 0.05 ) . Both drugs also increased serum high density lipoprotein ( HDL ) cholesterol ( placebo 1.15 + /- 0.29 , bezafibrate 1.27 + /- 0.38 ( P < 0.01 ) and gemfibrozil 1.26 + /- 0.49 ( P < 0.05 ) mmol/l ) and HDL3 cholesterol concentration ( placebo 0.59 + /- 0.12 , bezafibrate 0.72 + /- 0.23 ( P < 0.001 ) and gemfibrozil 0.70 + /- 0.24 ( P < 0.01 ) mmol/l ) . Serum apolipoprotein A1 ( apo A1 ) was increased ( P < 0.05 ) by bezafibrate compared to gemfibrozil ( placebo 103 + /- 26 , bezafibrate 111 + /- 28 and gemfibrozil 102 + /- 25 mg/dl ) and CETA from HDL to VLDL and LDL was decreased ( P < 0.05 ) by bezafibrate compared to placebo , but the apparent decrease with gemfibrozil did not achieve statistical significance ( placebo 39.6 + /- 17.7 , bezafibrate 32.3 + /- 14.7 and gemfibrozil 33.8 + /- 15.0 nmol/ml/h ) . Neither drug affected the circulating concentration of CETP . Plasma fibrinogen was increased ( P < 0.05 ) by gemfibrozil ( placebo 4.16 ( 3.38 - 4.71 ) and gemfibrozil 4.65 ( 4.05 - 5.77 ) g/l ) and was significantly lower ( P < 0.001 ) on bezafibrate ( 3.60 ( 3.18 - 4.54 ) g/l ) than on gemfibrozil treatment . There was a significant ( P < 0.05 ) increase in PAI-1 activity with bezafibrate and a similar trend with gemfibrozil ( placebo 41.2 ( 25.6 - 64.5 ) , bezafibrate 50.5 ( 35.1 - 73.9 ) and gemfibrozil 48.5 ( 31.5 - 5.4 U/l ) . Neither fibrate influenced plasma concentrations of PAI-1 nor were the activities of lecithin : cholesterol acyl transferase or paraoxonase affected . The major difference in the action of the two drugs on lipoprotein metabolism was the greater effect of gemfibrozil in decreasing the overall serum concentration of Sf 12 - 20 lipoproteins and the triglycerides in Sf 12 - 20 and 0 - 12 lipoproteins . Bezafibrate , however , increased serum apo A1 concentration and significantly decreased CETA . The two drugs also had different effects on the plasma fibrinogen levels , which increased with gemfibrozil and tended to
The estimated effects of fibrate therapy on plasma concentration and activity of PAI-1 were independent of treatment duration and changes in plasma triglyceride levels in the meta-regression analysis .
This meta- analysis of RCTs suggested that fibrate therapy does not reduce plasma concentration or activity of PAI-I. The putative benefits of fibrate therapy in patients with cardiovascular disease appear to be exerted via mechanisms independent of effects on PAI-1
OBJECTIVE The aim of this systematic review was to perform a meta- analysis of r and omized controlled trials ( RCTs ) examining the efficacy of fibrate therapy in reducing plasma concentration or activity of plasminogen activator inhibitor 1 ( PAI-1 ) .