title: Comparison of atorvastatin versus fenofibrate in reaching lipid targets and influencing biomarkers of endothelial damage in patients with familial combined hyperlipidemia.
abstract: Statins and fibrates have different effects on lipid abnormalities of familial combined hyperlipidemia (FCHL); thus, the selection of the first-line drug is troublesome. We evaluated to what extent monotherapy with a potent statin is more effective than fibrate in reaching the recommended lipid targets in FCHL. Fifty-six patients were randomized to receive optimal dosage of atorvastatin (n = 27) or 200 mg/d micronized fenofibrate (n = 29) for 24 weeks. To reach the optimal dosage, atorvastatin was up-titrated at each follow-up visit if low-density lipoprotein (LDL) cholesterol >130 mg/dL (>100 mg/dL in patients with coronary or cerebrovascular disease). The effects of fenofibrate and atorvastatin on lipoprotein fractions as well as on plasma levels of endothelin-1 (ET-1) and adrenomedullin (AM) were also evaluated. At end of trial, a greater proportion of patients on atorvastatin (average dosage, 20.8 mg/d) reached lipid targets in comparison with those on fenofibrate (64% vs 32.1%, P = .02). Atorvastatin was significantly more effective in reducing total cholesterol, LDL cholesterol, apolipoprotein B, and non-high-density lipoprotein (HDL) cholesterol. Conversely, triglycerides decreased and HDL increased more during fenofibrate. Nevertheless, atorvastatin produced a marked reduction in very low-density lipoprotein and very low-density lipoprotein remnants. Atorvastatin lowered all LDL subtypes, although fenofibrate appeared to be more effective on denser LDL. Compared with 43 normolipemic controls, FCHL patients presented increased baseline plasma levels of ET-1 (P = .007) but not of AM. Fenofibrate, but not atorvastatin, significantly lowered ET-1 levels by 16.7% (P < .05). Neither drug significantly affected plasma concentrations of AM. In summary, although fenofibrate showed superiority in raising HDL and reducing ET-1, atorvastatin was more effective in reaching lipid targets in FCHL so that it can be proposed as the first-line option in the management of this atherogenic hyperlipidemia.
authors.affiliation: Unit of Medical Therapy, Department of Clinical and Medical Therapy, University La Sapienza, Rome, Italy. marcelloarca@libero.it
authors.forename: Marcello
authors.initials: M
authors.lastname: Arca
authors.forename: Anna
authors.initials: A
authors.lastname: Montali
authors.forename: Giovanni
authors.initials: G
authors.lastname: Pigna
authors.forename: Roberto
authors.initials: R
authors.lastname: Antonini
authors.forename: Teresa Maria
authors.initials: TM
authors.lastname: Antonini
authors.forename: Petramala
authors.initials: P
authors.lastname: Luigi
authors.forename: Antonio
authors.initials: A
authors.lastname: Fraioli
authors.forename: Marco
authors.initials: M
authors.lastname: Mastrantoni
authors.forename: Maura
authors.initials: M
authors.lastname: Maddaloni
authors.forename: Claudio
authors.initials: C
authors.lastname: Letizia
mesh_terms: D000328:Adult; D000368:Aged; D000069059:Atorvastatin; D015415:Biomarkers / Q000097:blood*; D019332:Endothelin-1 / Q000097:blood; D004730:Endothelium, Vascular / Q000473:pathology*; D005260:Female; D011345:Fenofibrate / Q000627:therapeutic use*; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy*; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000627:therapeutic use*
chemical_list: D015415:Biomarkers; D019332:Endothelin-1; D006538:Heptanoic Acids; D000960:Hypolipidemic Agents; D011758:Pyrroles; D000069059:Atorvastatin; D011345:Fenofibrate