The safety, tolerability, and efficacy of a 12-wk treatment with pravastatin, 5, 10, and 20 mg/d, was evaluated in 72 children with heterozygous familial hypercholesterolemia (FH) in a double-blind, randomized and placebo-controlled study. The results show that pravastatin was well tolerated and that adverse events were mild and equally distributed among the three treatment groups. Plasma total and LDL cholesterol levels were significantly reduced in all pravastatin treatment groups, in comparison with the control group; -24.6% (-28.1 to 21.0) and -32.9% (-37.0 to -28.6), for mean change and 95% confidence interval, respectively. In four children plasma LDL cholesterol levels were reduced within normal limits for sex and age. HDL cholesterol increased in the pravastatin 20-mg group, +10.8% (+3.4 to +18.8), whereas plasma apo B100 and very LDL (VLDL) cholesterol levels were reduced within all pravastatin-treated groups -26.8% (-31.2 [corrected] to -21.7) and -24.5% (-35.0 to -12.3). These data show that short-term pravastatin treatment of children with FH is safe and effective, although long-term dose titration studies with 3-hydroxy-3-methylglutaryl-CoA reductase inhibitors need to be performed, to reduce plasma LDL cholesterol levels below a predefined level. The results of these studies have to be awaited before new treatment strategies are to be considered in these children.

SummaryWe assessed the safety and efficacy of the novel low molecular weight heparinoid Lomoparan (Org 10172) for the prevention of deep-vein thrombosis in patients undergoing elective total hip replacement in a randomized, placebo-controlled, double-blind trial in 197 consecutive patients. The heparinoid (750 anti-factor Xa-units, s. c., b.i.d.) was administered to 97 patients and 99 patients received placebo. Study medication was started preoperatively and continued for 10 days. Efficacy was assessed by bilateral phlebography at day 10, postoperatively.The incidence of deep-vein thrombosis was 56.6% and 15.5% respectively in the placebo and heparinoid treated patients (incidence reduction: 74%; P <0.001). This reduction was observed both for proximal-vein thrombosis (25% to 8%; P <0.005) and isolated calf-vein thrombosis (31% to 7%; P <0001.No major hemorrhage was observed. The number of red-cell units transfused and drain-fluid loss were comparable for the two study groups. Six patients in the heparinoid group and none in the control group developed minor wound hematomas (P <0.05).During an 8-week post-discharge follow-up period three patients with a normal venogram at day 10 developed clinically apparent venous thromboembolism, which was confirmed by objective testing. All three patients belonged to the heparinoid-treated group.We conclude that 750 anti-factor Xa units Org 10172 s.c. twice daily starting preoperatively is safe and effectively reduces early deep-vein thrombosis following elective total hip replacement. Further studies on the incidence of post-discharge thromboembolism are required.

SummaryEvaluation of fibrate treatment in humans has focused primarily on its anti-lipidaemic effects. A potentially favourable haemostasis-modulating activity of fibrates has also been recognized but the data are not consistent. We sought to learn more about this variability by examining the effects of gemfibrozil and ciprofibrate on plasma levels of tissue-type plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) and fibrinogen in primary hyperlipidaemic patients after six and twelve weeks of treatment using different assay systems for PAI-1 and fibrinogen. Although both fibrates effectively lowered triglyceride and cholesterol levels, no effect on the elevated baseline antigen levels of t-PA and PAI-1 was observed after fibrate treatment. However, both fibrates influenced plasma fibrinogen levels, albeit in a different 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, respectively, whereas with ciprofibrate there was no effect. Using a Clauss functional assay with either a mechanical end point or a turbidity-based end point, no significant change in fibrinogen levels was seen after six weeks of gemfibrozil treatment. However, after twelve weeks, gemfibrozil enhanced functional fibrinogen levels by 7.2% (p <0.05) as assessed by the Clauss mechanical assay, but decreased functional fibrinogen levels by 12.5% (p <0.0001) when a Clauss assay based on turbidity was used. After six or twelve weeks of ciprofibrate treatment, functional 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 14.2% (p <0.001) and 28.2% (p <0.0001), respectively with the Clauss turbidimetric assay. A remarkable and consistent finding with both fibrates was the decrease in functionality of fibrinogen as assessed by the ratio of functional fibrinogen (determined by either of the two Clauss assays) to fibrinogen antigen.Taken together, our results indicate that at least part of the variability in the effects of fibrates on haemostatic parameters can be explained by intrinsic differences between various fibrates, by differences in treatment period and/or by the different outcomes of various assay systems. Interestingly, the two fibrates tested both reduced the functionality of fibrinogen.

SummaryIn 196 consecutive patients who underwent elective total hip surgery we investigated the diagnostic accuracy of the thrombinantithrombin III complex immunoassay, as assessed on the first, fourth and tenth postoperative day, for the development of deep vein thrombosis (DVT). Patients received either LMWheparinoid (n = 97) or placebo (n = 99) and underwent contrast venography on the tenth postoperative day.Thrombin-antithrombin III (T-AT) plasma levels were raised in all patients on the first postoperative day and gradually decreased during the study period. T-AT plasma levels were significantly higher in patients developing DVT when compared to patients without DVT and remained so until day 10. This difference was apparent both in the LMW-heparinoid group as well as in the placebo-treated patients.ROC-curve analysis revealed no satisfactory discriminative power for the diagnosis of developing DVT at any of the studied cut-off values for T-AT.We conclude that the postoperative determination of T-AT complex plasma concentrations in hip surgery patients has no clinical utility in the prediction of postoperative DVT.

Both therapies exhibited their specific effects, although none of the drugs alone completely normalized the lipid profiles of these patients with FCH. Therefore, the choice of treatment should be based on the most elevated lipoprotein fraction, and in some cases a combination of the two drugs may be indicated.