title: Comparison of treatment of severe high-density lipoprotein cholesterol deficiency in men with daily atorvastatin (20 mg) versus fenofibrate (200 mg) versus extended-release niacin (2 g).
abstract: To determine whether available lipid-modifying medication can increase high-density lipoprotein (HDL) cholesterol in well-defined genetic or familial HDL-deficiency states, we studied 19 men with HDL deficiency (HDL cholesterol <5th percentile for age and gender) 55 +/- 10 years of age. Concomitant risk factors included diabetes (n = 3) and hypertension (n = 7) and 8 patients had coronary artery disease. Molecular analysis revealed that 4 patients had a mutation in the ABCA1 gene. Patients were assigned to sequentially receive atorvastatin 20 mg/day, fenofibrate 200 mg/day, and extended-release niacin 2 g/day for 8 weeks, with a 4-week washout period between each treatment. Patients in whom a statin was required, according to current treatment guidelines, were kept on atorvastatin throughout the study. Baseline HDL cholesterol level was 0.63 +/- 0.12 mmol/L (24 +/- 5 mg/dl), triglycerides 2.01 +/- 0.98 mmol/L (180 +/- 86 mg/dl), and low-density lipoprotein (LDL) cholesterol 2.29 +/- 0.95 mmol/L (94 +/- 39 mg/dl). Mean percent changes in HDL cholesterol on atorvastatin, fenofibrate, and niacin were -6% (p = NS), +6% (p = NS), and +22% (p <0.05), respectively. Furthermore, niacin significantly increased the large alpha-1 apolipoprotein A-I-containing HDL subspecies (12 to 17 nm). In conclusion, niacin was the only effective drug to increase HDL cholesterol. The absolute increase in HDL cholesterol, approximately 0.10 mmol/L (3.9 mg/dl), is of uncertain clinical significance. Biomarkers of HDL-mediated cellular cholesterol efflux were not changed by niacin therapy. Atorvastatin or fenofibrate had little effect on HDL cholesterol; atorvastatin decreased the total cholesterol/HDL cholesterol ratio by 26%. Fenofibrate did not change HDL cholesterol levels and caused an increase in LDL cholesterol. Aggressive LDL cholesterol lowering may be the strategy of choice in such patients.
authors.affiliation: Cardiovascular Research Laboratories, McGill University Health Center/Royal Victoria Hospital, Montréal, Québec, Canada.
authors.forename: Khalid
authors.initials: K
authors.lastname: Alrasadi
authors.forename: Zuhier
authors.initials: Z
authors.lastname: Awan
authors.forename: Khalid
authors.initials: K
authors.lastname: Alwaili
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ruel
authors.forename: Anouar
authors.initials: A
authors.lastname: Hafiane
authors.forename: Larbi
authors.initials: L
authors.lastname: Krimbou
authors.forename: Jacques
authors.initials: J
authors.lastname: Genest
mesh_terms: D000328:Adult; D000368:Aged; D000069059:Atorvastatin; D008076:Cholesterol, HDL / Q000172:deficiency*; D003677:Deficiency Diseases / Q000188:drug therapy; D011345:Fenofibrate / Q000008:administration & dosage*; D006538:Heptanoic Acids / Q000008:administration & dosage*; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009525:Niacin / Q000008:administration & dosage*; D010865:Pilot Projects; D011758:Pyrroles / Q000008:administration & dosage*; D012720:Severity of Illness Index
chemical_list: D008076:Cholesterol, HDL; D006538:Heptanoic Acids; D000960:Hypolipidemic Agents; D011758:Pyrroles; D009525:Niacin; D000069059:Atorvastatin; D011345:Fenofibrate