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)

• Published in: Journal of clinical lipidology 2012-07, Vol.6 (4), p.340-351
• Main Authors: Han, Ki Hoon, MD, Rha, Seung Woon, MD, Kang, Hyun-Jae, MD, Bae, Jang-Whan, MD, Choi, Byoung-Joo, MD, Choi, So-Yeon, MD, Gwon, Hyeon-Cheol, MD, Bae, Jang-Ho, MD, Hong, Bum-Kee, MD, Choi, Dong-Hoon, MD, Han, Kyoo-Rok, MD
• Format: Article
• Language: English
• Subjects: Adult; Aged; Alanine transaminase; Alanine Transaminase - blood; Atorvastatin; Atorvastatin Calcium; Cardiovascular; Cholesterol, LDL - blood; Drug Administration Schedule; Fatty Liver - diagnostic imaging; Female; Hepatic steatosis; Hepatotoxicity; Heptanoic Acids - therapeutic use; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors - therapeutic use; Hypercholesterolemia - blood; Hypercholesterolemia - drug therapy; Male; Middle Aged; Pitavastatin; Pyrroles - therapeutic use; Quinolines - therapeutic use; Tomography, X-Ray Computed; Triglycerides - blood
• ISSN: 1933-2874; 1876-4789
• DOI: 10.1016/j.jacl.2012.01.009

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. Methods and 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.