title: Pitavastatin 4 mg Provides Significantly Greater Reduction in Remnant Lipoprotein Cholesterol Compared With Pravastatin 40 mg: Results from the Short-term Phase IV PREVAIL US Trial in Patients With Primary Hyperlipidemia or Mixed Dyslipidemia.
abstract: OBJECTIVE
  Remnants are partially hydrolyzed, triglyceride-rich lipoproteins that are implicated in atherosclerosis. We assessed the adequacy of pitavastatin 4 mg and pravastatin 40 mg in reducing atherogenic lipid parameters beyond LDL-C, in particular remnant lipoprotein cholesterol (RLP-C).
  
  
  METHODS
  From the Phase IV, multicenter, randomized, double-blind PREVAIL US (A Study of Pitavastatin 4 mg Vs. Pravastatin 40 mg in Patients With Primary Hyperlipidemia or Mixed Dyslipidemia) trial, we examined lipoprotein cholesterol subfractions using Vertical Auto Profile testing and apolipoproteins B and A-I at baseline and 12 weeks. Participants with primary hyperlipidemia or mixed dyslipidemia had LDL-C levels of 130 to 220 mg/dL and triglyceride levels ≤ 400 mg/dL. In this post hoc analysis, changes in lipid parameters were compared by using ANCOVA.
  
  
  RESULTS
  Lipoprotein subfraction data were available in 312 patients (pitavastatin, n = 157; pravastatin, n = 155). Pitavastatin promoted a greater reduction in RLP-C than pravastatin (-13.6 [8.7] vs -9.3 [9.5] mg/dL). Furthermore, the pitavastatin group reported greater reductions in both components of RLP-C (both, P < 0.001): intermediate-density lipoprotein cholesterol (-9.5 [6.3] vs -6.4 [6.6] mg/dL) and very low-density lipoprotein cholesterol subfraction 3 (-4.1 [3.5] vs -2.9 [3.8] mg/dL). There were also greater reductions in the major ratios of risk (apolipoprotein B/apolipoprotein A-I and total cholesterol/HDL-C) (both, P < 0.001). There were no significant changes in HDL-C, its subfractions, or natural log lipoprotein(a)-cholesterol. The mean age was 58.8 ± 8.9 years in the pitavastatin group and 57.0 ± 10.2 years in the pravastatin group.
  
  
  CONCLUSIONS
  Compared with pravastatin 40 mg daily, pitavastatin 4 mg provided superior reductions in atherogenic lipid parameters beyond LDL-C, including RLP-C. Future studies are needed investigate the clinical implications of lowering directly measured RLP-C as the principal target. ClinicalTrials.gov identifier: NCT01256476.
authors.affiliation: Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, Maryland. Electronic address: elliottmiller@jhmi.edu.
authors.forename: P Elliott
authors.initials: PE
authors.lastname: Miller
authors.affiliation: Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, Maryland.
authors.forename: Seth S
authors.initials: SS
authors.lastname: Martin
authors.affiliation: Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, Maryland; Department of Medicine, Division of Cardiology, UT Southwestern Medical Center, Dallas, Texas.
authors.forename: Parag H
authors.initials: PH
authors.lastname: Joshi
authors.affiliation: Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, Maryland.
authors.forename: Steven R
authors.initials: SR
authors.lastname: Jones
authors.affiliation: Department of Biostatistics, Boston University School of Public Health, Boston, Massachusetts.
authors.forename: Joseph M
authors.initials: JM
authors.lastname: Massaro
authors.affiliation: Department of Mathematics and Statistics, Boston University, Boston, Massachusetts.
authors.forename: Ralph B
authors.initials: RB
authors.lastname: D'Agostino
authors.affiliation: Kowa Pharmaceuticals America, Inc, Montgomery, Alabama.
authors.forename: Craig A
authors.initials: CA
authors.lastname: Sponseller
authors.affiliation: Johns Hopkins Ciccarone Center for the Prevention of Heart Disease, Baltimore, Maryland; CGH Medical Center, Sterling, Illinois and the University of Illinois School of Medicine, Peoria, Illinois.
authors.forename: Peter P
authors.initials: PP
authors.lastname: Toth
mesh_terms: D000368:Aged; D002784:Cholesterol / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004311:Double-Blind Method; D050171:Dyslipidemias / Q000188:drug therapy*; D005260:Female; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy*; D008055:Lipids / Q000097:blood; D008074:Lipoproteins / Q000097:blood; D008297:Male; D008875:Middle Aged; D017035:Pravastatin / Q000627:therapeutic use*; D011804:Quinolines / Q000627:therapeutic use*
chemical_list: D008078:Cholesterol, LDL; D008055:Lipids; D008074:Lipoproteins; D011804:Quinolines; C030104:lipoprotein cholesterol; D002784:Cholesterol; D017035:Pravastatin; C108475:pitavastatin
keywords: hyperlipidemia; mixed dyslipidemia; pitavastatin; pravastatin; remnant lipoprotein cholesterol