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)

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, Donghoon Choi, Kyoo Rok Han

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)340-351
Number of pages12
JournalJournal of Clinical Lipidology
Volume6
Issue number4
DOIs
Publication statusPublished - 2012 Jul 1

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Hydroxymethylglutaryl-CoA Reductase Inhibitors
Hypercholesterolemia
Alanine Transaminase
Safety
Liver
Serum
LDL Cholesterol
Enzymes
Coenzyme A
Random Allocation
Alanine
Hydroxyl Radical
Hepatitis
Oxidoreductases
Biomarkers
Atorvastatin Calcium
pitavastatin
Therapeutics
Pharmaceutical Preparations

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics
  • Cardiology and Cardiovascular Medicine

Cite this

@article{22952ff0523348e688963d30fc0aace7,
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. 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.",
author = "Han, {Ki Hoon} and Rha, {Seung Woon} and Kang, {Hyun Jae} and Bae, {Jang Whan} and Choi, {Byoung Joo} and Choi, {So Yeon} and Gwon, {Hyeon Cheol} and Bae, {Jang Ho} and Hong, {Bum Kee} and Donghoon Choi and Han, {Kyoo Rok}",
year = "2012",
month = "7",
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doi = "10.1016/j.jacl.2012.01.009",
language = "English",
volume = "6",
pages = "340--351",
journal = "Journal of Clinical Lipidology",
issn = "1933-2874",
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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). / Han, Ki Hoon; Rha, Seung Woon; Kang, Hyun Jae; Bae, Jang Whan; Choi, Byoung Joo; Choi, So Yeon; Gwon, Hyeon Cheol; Bae, Jang Ho; Hong, Bum Kee; Choi, Donghoon; Han, Kyoo Rok.

In: Journal of Clinical Lipidology, Vol. 6, No. 4, 01.07.2012, p. 340-351.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Evaluation of short-term safety and efficacy of HMG-CoA reductase inhibitors in hypercholesterolemic patients with elevated serum alanine transaminase concentrations

T2 - PITCH study (PITavastatin versus atorvastatin to evaluate the effect on patients with hypercholesterolemia and mild to moderate hepatic damage)

AU - Han, Ki Hoon

AU - Rha, Seung Woon

AU - Kang, Hyun Jae

AU - Bae, Jang Whan

AU - Choi, Byoung Joo

AU - Choi, So Yeon

AU - Gwon, Hyeon Cheol

AU - Bae, Jang Ho

AU - Hong, Bum Kee

AU - Choi, Donghoon

AU - Han, Kyoo Rok

PY - 2012/7/1

Y1 - 2012/7/1

N2 - 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.

AB - 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.

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DO - 10.1016/j.jacl.2012.01.009

M3 - Article

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JO - Journal of Clinical Lipidology

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