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The effect of orlistat, a nonabsorbed inhibitor of gastric and pancreatic lipases, was examined in patients with primary hyperlipidaemia (serum cholesterol ≥6.2 mmol·l and triglycerides ≤5.0 mmol·l not responsive to dietary change alone. In a multicentre, randomised, double-blind study, 103 men and 70 women received 30, 90, 180, or 360 mg of orlistat or placebo for 8 weeks. Total and low-density lipoprotein cholesterol levels were reduced by 4% and 5% with 30 mg orlistat, by 7% and 8% with 90 mg orlistat, by 7% and 7% with 180 mg orlistat and by 11% and 10% with 360 mg orlistat compared to placebo. High density lipoprotein cholesterol levels significantly decreased in the 360 mg orlistat group. Triglyceride levels significantly increased in the placebo group but not in the drug groups. Body weight decreased by 1.2 kg with 360 mg orlistat, despite a weight maintenance diet. Decreases in vitamin E and D levels occurred, although both vitamins remained within the normal range. Adverse effects from the gastrointestinal tract were frequent, but led to discontinuation of therapy in only seven patients. Orlistat is a new therapeutic drug for the treatment of hyperlipidaemia that may be particularly useful among overweight patients. Its potential place in therapy will await long-term studies. Vitamin supplementation should be considered during treatment. [ABSTRACT FROM AUTHOR]

The efficacy and safety of the HMG CoA reductase inhibitor fluvastatin have been evaluated in a double blind study in 52 patients with familial hypercholesterolaemia. A standard AHA Phase II lipid lowering diet was prescribed throughout the study. After 6 weeks of a single blind dosage stabilisation period, in which patients received fluvastatin 40 mg qPM, patients were randomly allocated to one of two double blind treatment groups: group A (n=24) received fluvastatin 20 mg b. d. for 12 weeks and fluvastatin 20 mg AM + 40 mg PM for an additional 12 weeks; Group B (n=28) received fluvastatin 40 mg qPM during the entire study. Safety and tolerability were evaluated by the analysis of biochemical and haematological parameters, and ophthalmological and physical examinations. Efficacy was analysed by the determination of plasma lipids, lipoproteins and apoproteins. Fluvastatin 40 mg/d was associated with up to a 27.4% decrease in LDL-C and a 9.6% increase in HDL-C concentrations. Increasing the dose of fluvastatin from 20 mg b. d. to 60 mg per day in Group A was associated with a 7.1% decrease in LDL-C, a 12.1% increase of HDL-C and a 12.8% decrease in the LDL-C/HDL-C ratio. In comparison with Group B (40 mg qPM) LDL-C, HDL-C and the LDL-C/HDL-C ratio in Group A (60 mg) differed by −8.9%, 6.6% and −12%, respectively. During treatment with 40 mg qPM, one patient developed an asymptomatic but notable elevation of CK to 1823 U/l (normal range 0-100 U/l) that was caused by strenuous exercise. No other notable biochemical or haematological abnormalities were recorded. It is concluded that in patients with heterozygous FH the increase of fluvastatin from 40 to 60 mg/d provided an additional significant effect on plasma LDL-C and HDL-C levels and in the LDL-C/HDL-C ratio, without producing any deleterious effect. [ABSTRACT FROM AUTHOR]

The relationship between the content of probucol in plasma and lipid lowering was studied after administration of probucol. The study group consisted of 44 patients with Type II hyperlipidaemia (mean age 56 y). Total cholesterol level was decreased from 293 to 232 mg · dl by the administration of probucol. The plasma probucol concentration was 2.03 mg · dl after 4 weeks of administration of 500 mg b. d. Although there was no relationship between the change in total cholesterol and the plasma probucol, a linerar relation was observed between the decrease in LDL-cholesterol concentration and the probucol concentration in LDL. Neither the VLDL nor the HDL-probucol content were related to the magnitude of the decrease in lipoprotein cholesterol. The present study has demonstrated that an increase in the probucol content in LDL was associated with a decrease in plasma LDL-cholesterol. [ABSTRACT FROM AUTHOR]

Cyclosporine (Cy) binds to lipoproteins in plasma. In order to test if its pharmacokinetics would be modified when efficient lipid-lowering treatment is introduced, a study has been done of Cy pharmacokinetics and any interaction with the lipid-lowering agent fenofibrate in hyperlipidaemic long-term, survivors of heart transplantation. Fenofibrate 200 mg once daily significantly reduced blood lipids (cholesterol 6.5 vs 7.7 mmol/l; apoprotein B 1.2 vs 1.6 g/l) but did not modify mean whole blood Cy trough levels (113 before fenofibrate vs 103 ng·ml), C (812 ng·ml by RIA and 757 ng·ml by HPLC before fenofibrate versus 865 and 741 respectively, during fenofibrate); t (1.6 and 1.7 h before fenofibrate versus 1.4 and 1.4 h respectively), and t (13.9 and 11.1 h versus 9.5 and 10.7 h). The only adverse effect was an increase in creatinine (157 vs 145 mmol/l). Further studies are needed to investigate the mechanism of Cy-fenofibrate nephrotoxicity and to evaluate the long-term efficiency and safety of fenofibrate after heart transplantation. [ABSTRACT FROM AUTHOR]

The antihyperlipidaemic effect of a guar preparation which absorbs a particularly large amount of water has been examined in 13 patients with Type II hyperlipidaemia. A 30-day pre-treatment phase was followed by 60 days of treatment with 4 g guar dissolved in 200-ml liquid at each meal-time (total guar 12 g/day), and a 60-day post-treatment observation period. Routine other clinical blood tests were performed 30, 15 or 0 days before treatment, 15, 30 and 60 days after the start of treatment, and 30 and 60 days after its end. Total cholesterol fell by 0.85 mmol·l, from a pre-treatment concentration of 7.4 mmol·l to a treatment value of 6.5 mmol·l, and LDL-cholesterol fell by 0.64 mmol·l, from 5.5 mmol·l to a treatment value of 4.8 mmol·l. There was no significant change in triglyceride and VLDL concentrations during the study. A slight but significant fall in HDL-cholesterol was seen. The sole adverse effect was occasional intestinal discomfort. [ABSTRACT FROM AUTHOR]

This is the first long-term study of pindolol in a population-based sample of men with newly diagnosed hypertension. Eighty-two patients, with a diastolic pressure of 100 mm Hg or more, were identified after screening 6000 men. Many patients were overweight. 82 population controls, matched by sex, age and body mass index, were also recruited. Fourty-eight per cent of the patients and 25% of the controls had a family history of hypertension. Serum triglyceride and urate values were higher in patients than controls at the baseline investigation. Seventy-four patients were followed for 1 year. The dose of pindolol averaged 7.7 mg once daily after 1 year. The diastolic blood pressure was reduced by 13.4 mm Hg. The target pressure of 95 mm Hg or less was achieved in 89% of the patients. The HDL-cholesterol concentration was normal and did not change, whereas the LDL-cholesterol concentration decreased by 0.15 mmol · l during treatment. The total triglyceride values increased transiently up to 6 months, but no significant increase was seen after one year. It is concluded that pindolol had no adverse effect on serum cholesterol and its HDL- and LDL-fractions during 1 year of treatment. [ABSTRACT FROM AUTHOR]

Chronic renal insufficiency is often accompanied by hyperlipidaemia and subsequent coronary heart disease. Two groups of 15 patients with serum creatinine >2 mg/100 ml and serum cholesterol >250 mg/100 ml were given 3×50 mg magnesium pyridoxal 5-phosphate glutamate (MPPG) or placebo for 12 weeks in a double-blind, randomised study. Total cholesterol in the MPPG group (282.4 mg·100 ml) was lower than in the placebo group (354.3 mg·100 ml) after 12 weeks of treatment. Triglycerides in the MPPG group were 265.1 mg·100 ml compared to 361.9 mg·100 ml. After 12 weeks on MPPG the LDL/HDL ratio of 3.56 was lower than in the placebo group - 6.83. Side effects in the MPPG group were similar to those in the placebo group. Thus, MPPG was an effective antihyperlipidaemic agent in patients with renal insufficiency. [ABSTRACT FROM AUTHOR]

Fifty-two patients with Fredrickson Type IIb or Type IV hyperlipidaemia, in whom diet had not achieved satisfactory lipid levels, completed a double blind randomised study of acipimox versus placebo. The patients were given acipimox, 250 mg three times daily or placebo for a three month period, and plasma lipids and glucose were monitored. The patients receiving acipimox showed a fall in the mean concentration of plasma triglyceride compared to placebo (0.74 mmol/l) and this was most marked in patients whose initial plasma triglyceride levels were greater than 3 mmol/l (1.0 mmol/l, confidence limits 0.18, 1.82). Acipimox was well tolerated, and could be a useful addition to the drugs available for the treatment of patients with hypertriglyceridaemia. [ABSTRACT FROM AUTHOR]

The an tihypertensive and metabolic effects of oral nicardipine SR 40 mg b. i. d. have been studied in 18 (15 m, 3 f; age 52.7 y) hypertensives with mild hypercholesterolaemia, treated for 3 months after a 2 week period on placebo. An iv Fat Tolerance Test (FTT) was also performed in 8 patients following placebo, treatment with acute nicardipine 20 mg and chronic administration of nicardipine SR. There was a significant fall in BP from 160/97 on placebo to 147/87 after 3 months on nicardipine SR with no change in heart rate. Blood lipids did not change significantly. The disappearance rate of the lipid emulsion in the ivFTT showed no significant change (K2 was 1.93% /min after placebo, 1.84 after nicardipine 20 mg and 1.71 after chronic treatment). The results suggest that nicardipine is an effective antihypertensive drug and that it is devoid of untoward effects on lipid metabolism. [ABSTRACT FROM AUTHOR]

Clofibrate inhibits the synthesis of adrenal steroids when administered in vitro. In the present study the effect in vivo of clofibrate on adrenal steroid secretion has been investigated. Basal levels of plasma progesterone, corticosterone, aldosterone, 17-hydroxyprogesterone, 11-deoxycortisol, cortisol, dehydroepiandrosterone sulphate and dehydroepiandrosterone, and their response to ACTH 1 mg im, were not reduced by chronic administration of clofibrate 2 g per day p.o. for 8 to 34 days to 6 hyperlipidaemic men. [ABSTRACT FROM AUTHOR]