Antilipemic agents

OBJECTIVES: The aim of this study was to evaluate the frequency, characteristics and risk factors of lipid changes associated with lopinavir/ritonavir treatment in antiretroviral-naive patients. METHODS: A prospective cohort of 107 antiretroviral-naive HIV-infected patients was followed for 12 months after starting lopinavir/ritonavir-based highly active antiretroviral therapy. RESULTS: At 12 months, percentages of patients with hypercholesterolaemia and hypertriglyceridaemia were 17.4% and 40%, respectively. Mean increases in total cholesterol and triglycerides were 40.7 and 73.3 mg/dL. There was a significant increase in both low-density and high-density (HDL) cholesterol, and no increase in the total cholesterol/HDL ratio (from 4.16 at baseline to 4.49 after 12 months). Baseline cholesterol > 200 mg/dL and triglycerides > 150 mg/dL were independent risk factors for dyslipidaemia, while hepatitis C coinfection appeared to be protective. CONCLUSIONS: Patients with elevated lipid values at baseline have the greatest risk of developing hypercholesterolaemia and hypertriglyceridaemia after starting lopinavir/ritonavir. Antiretroviral-naive patients coinfected with hepatitis C have a low risk of developing hyperlipidaemia after starting lopinavir/ritonavir.

BACKGROUND: Statins reduce cardiovascular events to a greater extent than can be explained by their effect on lipids. Several studies have attempted to elucidate mechanisms by which statins reduce cardiovascular risk. PURPOSE: To summarize the effects of statins on nonlipid serum markers and to correlate statins' effect on serum markers with lipid levels and cardiovascular outcomes. DATA SOURCES: MEDLINE (1980 to 2003) search limited to English-language articles. STUDY SELECTION: Studies reporting original data in at least 10 participants on the effect of statins on outcomes of interest, excluding studies of cerivastatin, drug combinations, and patients with organ transplants. DATA EXTRACTION: Study design, sample size, treatment, and outcome data extracted on the basis of preestablished criteria. When appropriate, meta-analysis was performed by using a random-effects model. DATA SYNTHESIS: All statins are effective at lowering C-reactive protein levels, and the effect is not dose-dependent. Studies do not demonstrate a correlation between statins' effects on C-reactive protein levels and on lipids or cardiovascular outcomes. Statins do not affect fibrinogen levels, and limited data suggest little effect on lipid oxidation, tissue plasminogen activator, or plasminogen activator inhibitor. Platelet aggregation data are inconclusive. CONCLUSIONS: Among nonlipid serum markers examined, only C-reactive protein levels are statistically significantly affected by statins. These findings suggest that statin-mediated anti-inflammatory effects may contribute to the ability of statins to reduce risk for cardiovascular disease. Overall, however, available data are insufficient to support recommendations for using nonlipid serum markers in decisions regarding statin therapy for individual patients.

Int J Artif Organs. 1995 Dec;18(12):786-93.
Four years' treatment efficacy of patients with severe hyperlipidemia. Lipid lowering drugs versus LDL-apheresis.
Schiel R, Bambauer R, Muller UA.
Department of Internal Medicine II, University of Jena Medical School, Germany.

A total of 47 patients suffering from heterozygous hyperlipidemia were treated with LDL-apheresis (24 patients, aged 49.5 +/- 11.5 years), diet and/or lipid-lowering drugs or with diet and lipid-lowering drugs only (23 patients, aged 48.0 +/- 11.9 years). After treatment periods of 44.4 +/- 14.3 (apheresis group) and 33.5 +/- 15.9 (drug group) months, respectively, the ensuing results revealed significant differences (p < 0.0001): total cholesterol decreased from 10.4 to 5.5 vs 9.9 to 8.7 mmol/l, LDL from 7.4 to 3.9 vs 6.6 to 5.2 mmol/l, triglycerides from 5.8 to 3.7 vs 4.8 to 4.1 mmol/l and the LDL/HDL-ratio decreased from 7.1 to 3.4 vs 6.7 to 5.8. In the apheresis group one patient died from myocardial infarction vs one non-fatal myocardial infarction and the manifestation of coronary heart disease in three cases in the drug group. There were no severe side-effects in either group. All patients in the apheresis group experienced an increased clinical performance. On the other hand physological well-being of these patients was lower than that of the drug group (scores 42.3 +/- 8.9 vs 50.2 +/- 9.9, p < 0.002). The present trial suggests that a continuing reduction in serum lipid concentrations may lower in a dose dependent manner the risk of development and progression of coronary heart disease. With respect to clinical and laboratory results, LDL-apheresis seems safe and appears to be the most effective therapy.

First clinical results are presented for two newly developed drugs. Both are diphenylmethane derivatives named ethyl-(+/-)-2-([alpha-(p-chlorophenyl)-p-tolyl]-oxy)-2-methylbutyrate (beclobrate, B) and (+/-)-2-(4-[(4-chlorophenyl)methyl]phenoxy)-2-methyl-butanacid-3-pyridinylmethylester (eniclobrate, E). These drugs were given in a doubleblind crossover trial with placebo periods before, in between and afterwards to 6 patients with type IIb and 13 patients with type IIa hyperlipidemia. Beclobrate was given in a dosage of 100 mg twice daily and eniclobrate in a dosage of 130 mg twice daily. Besides effectively reducing LDL-cholesterol in type IIa there was a remarkable increase in HDL-cholesterol in both types of hyperlipidemia especially for beclobrate.