title: Comparative efficacy of pitavastatin and simvastatin in high-risk patients: a randomized controlled trial.
abstract: BACKGROUND
  Despite the proven efficacy of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins) in lowering total and low-density lipoprotein cholesterol (LDL-C), many patients do not reach recommended lipid targets. This study compared pitavastatin, a new and highly effective statin, and simvastatin in patients at high risk of coronary heart disease (CHD). The primary objective was to demonstrate noninferiority of pitavastatin to simvastatin.
  
  
  METHODS
  The study was a phase 3, randomized, double-blind, double-dummy, parallel-group, active-controlled study conducted at 37 centers in five European countries. Following a dietary run-in period of 6-8 weeks, patients with primary hypercholesterolemia or combined dyslipidemia and at least two CHD risk factors were randomized 2:1 to receive pitavastatin 4 mg or simvastatin 40 mg once daily for 12 weeks. The primary efficacy variable was the change in LDL-C from baseline.
  
  
  RESULTS
  In total, 355 patients were randomized, 236 to pitavastatin and 119 to simvastatin; 330 patients (223 and 107, respectively) completed the study. In the pitavastatin group, mean (± SD) reduction in LDL-C concentrations from baseline was -44.0 ± 12.8% compared with -43.8 ± 14.4% in the simvastatin group. The adjusted mean treatment difference (simvastatin--pitavastatin) was 0.31% (95% confidence interval -2.47, 3.09; P = 0.829), which was within the predefined noninferiority range. More than 80% of patients in each group reached recommended LDL-C targets. Pitavastatin provided a greater increase in high-density lipoprotein cholesterol (HDL-C; 6.8% vs. 4.5%; P = 0.083) and a significantly greater decrease in triglycerides (-19.8% vs. -14.8%; P = 0.044) than simvastatin. Both treatments were well tolerated.
  
  
  CONCLUSIONS
  Pitavastatin 4 mg is as effective as simvastatin 40 mg in lowering LDL-C in dyslipidemic patients at high risk of CHD, with additional effects on HDL-C and triglycerides. Therefore, pitavastatin may be appropriate for the management of dyslipidemic patients at high cardiovascular risk.
authors.affiliation: Department of Endocrinology, Metabolism & Diabetes, Karolinska University Hospital, M63 SE14186, Stockholm, Sweden. mats.eriksson@ki.se
authors.forename: Mats
authors.initials: M
authors.lastname: Eriksson
authors.forename: Dragos
authors.initials: D
authors.lastname: Budinski
authors.forename: Neil
authors.initials: N
authors.lastname: Hounslow
mesh_terms: D000368:Aged; D008078:Cholesterol, LDL / Q000097:blood; D003327:Coronary Disease / Q000517:prevention & control; D050171:Dyslipidemias / Q000097:blood / Q000188:drug therapy*; D005260:Female; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011804:Quinolines / Q000627:therapeutic use*; D019821:Simvastatin / Q000009:adverse effects / Q000627:therapeutic use*
chemical_list: D008078:Cholesterol, LDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011804:Quinolines; D019821:Simvastatin; C108475:pitavastatin