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)
Journal of Clinical Lipidology, 08/01/2012
Han KH et al. - Conventional doses of pitavastatin and atorvastatin effectively and safely reduce elevated hepatic enzyme concentrations.Methods
- 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).