title: Evaluation of short-term safety and efficacy of HMG-CoA reductase inhibitors in hypercholesterolemic patients with elevated serum alanine transaminase concentrations: PITCH study (PITavastatin versus atorvastatin to evaluate the effect on patients with hypercholesterolemia and mild to moderate hepatic damage).
abstract: BACKGROUND
  We evaluated the safety and efficacy of the 3-hydroxyl-3-methylglutaryl coenzyme A reductase inhibitors atorvastatin and pitavastatin in patients with mild-to-moderate increased levels of hepatic enzymes.
  
  
  RESULTS
  In this 12-week, prospective, randomized, open-label, active drug-controlled, and dose-titration study, 189 subjects with elevated low-density lipoprotein cholesterol (≥3.36 mmol/L) and alanine transaminase (ALT; ×1.25≥ and ≤×2.5 ULN; 50-100 IU/L) concentrations, but nonalcoholic and serologically negative for viral hepatitis markers at screening, were randomized to 12 weeks of treatment with pitavastatin 2-4 mg/day (PITA, n = 97) or atorvastatin 10-20 mg/day (ATOR, n = 92). Pitavastatin and atorvastatin equally reduced low-density lipoprotein cholesterol concentrations (-34.6 ± 16.0% and -38.1 ± 16.2%, respectively, P < .0001 each by analysis of variance). Seven (n = 4 PITA, n = 3 ATOR) and 10 (n = 5 PITA, n = 5 ATOR) patients experienced episodes of ALT >100 IU/L at weeks 4 and 12, respectively, with one patient in each group excluded because of severe ALT elevation >3× ULN (>120 IU/L) at week 4. The 135 patients with persistently increased ALT concentrations at screening and randomization showed significant reductions in ALT after 12 weeks of treatment with PITA (n = 68, -8.4%) or ATOR (n = 67, -8.9%; P < .05, analysis of variance). Serial nonenhanced computed tomography in 38 subjects (n = 18 PITA, n = 20 ATOR) showed that both statins reduced the severity of hepatic steatosis, especially in subjects with clear hepatic steatosis at baseline (n = 9 PITA, n = 10 ATOR). Statin treatment of another 38 subjects with spontaneous normalization of ALT at randomization had little effect on ALT levels but did not induce severe ALT elevation (>100 IU/L).
  
  
  CONCLUSIONS
  Conventional doses of pitavastatin and atorvastatin effectively and safely reduce elevated hepatic enzyme concentrations.
authors: Asan Medical Center, University of Ulsan, 388-1 Pungnap-2 dong Songpa-gu 138-736, Seoul, Republic of Korea.
authors: Ki Hoon
authors: KH
authors: Han
authors: Seung Woon
authors: SW
authors: Rha
authors: Hyun-Jae
authors: HJ
authors: Kang
authors: Jang-Whan
authors: JW
authors: Bae
authors: Byoung-Joo
authors: BJ
authors: Choi
authors: So-Yeon
authors: SY
authors: Choi
authors: Hyeon-Cheol
authors: HC
authors: Gwon
authors: Jang-Ho
authors: JH
authors: Bae
authors: Bum-Kee
authors: BK
authors: Hong
authors: Dong-Hoon
authors: DH
authors: Choi
authors: Kyoo-Rok
authors: KR
authors: Han
mesh_terms: D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood*; D000069059:Atorvastatin; D008078:Cholesterol, LDL / Q000097:blood; D004334:Drug Administration Schedule; D005234:Fatty Liver / Q000000981:diagnostic imaging; D005260:Female; D006538:Heptanoic Acids / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000627:therapeutic use*; D006937:Hypercholesterolemia / Q000097:blood / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000627:therapeutic use*; D011804:Quinolines / Q000627:therapeutic use*; D014057:Tomography, X-Ray Computed; D014280:Triglycerides / Q000097:blood
chemical_list: D008078:Cholesterol, LDL; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D011804:Quinolines; D014280:Triglycerides; D000069059:Atorvastatin; D000410:Alanine Transaminase; C108475:pitavastatin