(3S-5S-6E)-7-[3-(4-fluorophenyl)-1-(propan-2-yl)-1H-indol-2-yl]-3-5-dihydroxyhept-6-enoic-acid and Hypertriglyceridemia

Hyperlipidemia is an important cardiovascular risk factor. Lipid-lowering therapy has been shown to decrease morbidity and mortality in these patients. Combination therapy with a 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor and a fibric-acid derivative has been reported to be more efficacious to reduce low-density lipoprotein (LDL) cholesterol and triglycerides but may be associated with an increased risk of myositis. The aim of this study was to investigate the efficacy and tolerability of fluvastatin, an HMG-CoA reductase inhibitor, alone and in combination with bezafibrate, a fibric-acid derivative. In a randomized controlled trial with 454 hypercholesterolemic patients (mean cholesterol, 8.6 +/- 1.6 mM), fluvastatin (20 mg/day) significantly lowered total plasma cholesterol levels (-12.5%; p < 0.0001 vs. placebo), LDL cholesterol (-14%; p < 0.0001), and triglycerides (-4%; p = 0.05). A small increase in high-density lipoprotein (HDL) cholesterol levels (3%, NS) also was observed. Combination therapy with fluvastatin and bezafibrate (400 mg/day) in 71 patients with persistent hypertriglyceridemia during treatment with the statin resulted in a more pronounced reduction in triglyceride (-47%; p < 0.0001) and total cholesterol levels (-15%; p < 0.0001) than did fluvastatin alone. Furthermore, the additional bezafibrate significantly increased HDL cholesterol (+5%; p < 0.001). No significant increases in creatine phosphokinase levels or in frequency of myalgia were observed. In summary, fluvastatin decreases both cholesterol and triglyceride levels. In patients with persistent hypertriglyceridemia, combination therapy with fluvastatin and bezafibrate may be safely used to lower triglyceride and cholesterol levels more efficiently.

Topics: Adult; Aged; Bezafibrate; Cholesterol; Double-Blind Method; Drug Therapy, Combination; Fatty Acids, Monounsaturated; Female; Fluvastatin; Hemodynamics; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Hypertriglyceridemia; Hypolipidemic Agents; Indoles; Male; Middle Aged

We studied the effects of fluvastatin and bezafibrate in monotherapy and in combination on plasma fibrinogen, t-plasminogen activator inhibitor (PAI-1) and C reactive protein (CRP) in patients with coronary artery disease (CAD) and mixed hyperlipidaemia.. In this randomised, double blind, multicentre trial 333 patients with stable angina pectoris or previous myocardial infarction or coronary revascularisation and mixed hyperlipidaemia (LDL-cholesterol 135-250 mg/dl and triglycerides (TG) 180-400 mg/dl) were randomised to fluvastatin 40 mg, bezafibrate 400 mg, fluvastatin 20 mg + bezafibrate 400 mg or fluvastatin 40 mg + bezafibrate 400 mg treatments for 24 weeks.. Plasma fibrinogen significantly decreased after treatment with the combinations fluvastatin+bezafibrate (-14 and -16%) and with bezafibrate monotherapy (-9%). No significant reduction was observed after fluvastatin monotherapy (-4%). No significant changes were observed in PAI-1 and CRP plasma levels. Combination therapy significantly decreased both LDL-C and TG, and significantly increased HDL-C.. The combined effects on fibrinogen and plasma lipids achieved by fluvastatin and bezafibrate combination treatment might be more useful than the simple reduction of cholesterol in preventing ischaemic cardiovascular disease.

Topics: Adult; Aged; Bezafibrate; C-Reactive Protein; Cholesterol, LDL; Coronary Disease; Double-Blind Method; Drug Synergism; Drug Therapy, Combination; Fatty Acids, Monounsaturated; Female; Fibrinogen; Fluvastatin; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemia, Familial Combined; Hyperlipoproteinemia Type II; Hypertriglyceridemia; Hypolipidemic Agents; Indoles; Male; Middle Aged; Tissue Plasminogen Activator; Treatment Outcome

Topics: Angioplasty, Balloon, Coronary; Anticholesteremic Agents; Atorvastatin; Fatty Acids, Monounsaturated; Fluvastatin; Heptanoic Acids; Humans; Hypercholesterolemia; Hyperlipidemias; Hypertriglyceridemia; Indoles; Pyrroles

Topics: Adult; Anticholesteremic Agents; Drug Administration Schedule; Fatty Acids, Monounsaturated; Female; Fluvastatin; HIV Infections; HIV Protease Inhibitors; Humans; Hyperlipidemias; Hypertriglyceridemia; Indoles; Male

Topics: Anticholesteremic Agents; Fatty Acids, Monounsaturated; Fluvastatin; Humans; Hypercholesterolemia; Hypertriglyceridemia; Indoles; Thrombomodulin

The effects of fluvastatin, a new inhibitor of 3-hydroxy-3-methylglutaryl coenzyme A reductase, on the hyperlipidemia associated with nephrosis were studied. Nephrotic rats, induced by a single intraperitoneal injection of puromycin aminonucleoside (100 mg/kg body weight), had significantly higher plasma triglyceride (TG), total cholesterol and apoprotein (apo) B concentrations than controls. Fluvastatin was administrated as a 0.01% solution in drinking water for 14 days to either normal control or nephrotic rats. Concentrations of TG and apo B in plasma, and very low-density lipoprotein (VLDL) in nephrosis were completely normalized by the treatment with fluvastatin, but concentrations of cholesterol in plasma and each lipoprotein fraction were not altered by the treatment. The ratio of apo E to C in VLDL was significantly decreased in nephrotic rats, but the fluvastatin treatment increased this ratio. TG secretion rate estimated by the Triton WR1339 method was significantly increased in nephrotic rats, but was normalized by fluvastatin. Percent composition of TG in newly secreted VLDL particles in post-Triton plasma was not decreased by fluvastatin treatment, suggesting that the number of newly secreted VLDL particles was reduced by the treatment. Postheparin plasma lipolytic activities were not affected by the fluvastatin treatment. These results demonstrate that fluvastatin can effectively ameliorate the high concentration of VLDL by suppressing the hepatic secretion in nephrotic rats, and suggest that an inhibition of cholesterol biosynthesis suppresses VLDL secretion from the liver.

Topics: Animals; Anticholesteremic Agents; Apolipoproteins B; Cholesterol, LDL; Drinking; Eating; Fatty Acids, Monounsaturated; Fluvastatin; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hypertriglyceridemia; Indoles; Isoelectric Focusing; Lipoproteins, VLDL; Male; Nephrotic Syndrome; Puromycin Aminonucleoside; Rats; Rats, Wistar; Triglycerides