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.

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.

• Authors: Ki Hoon Han, Seung Woon Rha, Hyun-Jae Kang, Jang-Whan Bae, Byoung-Joo Choi, So-Yeon Choi, Hyeon-Cheol Gwon, Jang-Ho Bae, Bum-Kee Hong, Dong-Hoon Choi, Kyoo-Rok Han
• Journal: Journal of clinical lipidology (J Clin Lipidol) 2012 Jul-Aug Vol. 6 Issue 4 Pg. 340-51 ISSN: 1933-2874 [Print] United States
• PMID: 22836071 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2012 National Lipid Association. Published by Elsevier Inc. All rights reserved.

Chemical References

• Cholesterol, LDL
• Heptanoic Acids
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Pyrroles
• Quinolines
• Triglycerides
• Atorvastatin
• Alanine Transaminase
• pitavastatin

Topics

• Adult
• Aged
• Alanine Transaminase (blood)
• Atorvastatin
• Cholesterol, LDL (blood)
• Drug Administration Schedule
• Fatty Liver (diagnostic imaging)
• Female
• Heptanoic Acids (therapeutic use)
• Humans
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (therapeutic use)
• Hypercholesterolemia (blood, drug therapy)
• Male
• Middle Aged
• Pyrroles (therapeutic use)
• Quinolines (therapeutic use)
• Tomography, X-Ray Computed
• Triglycerides (blood)