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, Dong Hoon Choi, Kyoo Rok Han

Research output: Contribution to journalArticle

42 Citations (Scopus)

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

Fingerprint

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

Keywords

  • Alanine transaminase
  • Atorvastatin
  • Hepatic steatosis
  • Hepatotoxicity
  • Pitavastatin

ASJC Scopus subject areas

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

Cite this

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, Dong Hoon; Han, Kyoo Rok.

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

Research output: Contribution to journalArticle

@article{9f73b50488c84b399541c0237c8462e9,
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.",
keywords = "Alanine transaminase, Atorvastatin, Hepatic steatosis, Hepatotoxicity, Pitavastatin",
author = "Han, {Ki Hoon} and Seung-Woon Rha 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 Choi, {Dong Hoon} and Han, {Kyoo Rok}",
year = "2012",
month = "7",
day = "1",
doi = "10.1016/j.jacl.2012.01.009",
language = "English",
volume = "6",
pages = "340--351",
journal = "Journal of Clinical Lipidology",
issn = "1933-2874",
publisher = "Elsevier BV",
number = "4",

}

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, Dong Hoon

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.

KW - Alanine transaminase

KW - Atorvastatin

KW - Hepatic steatosis

KW - Hepatotoxicity

KW - Pitavastatin

UR - http://www.scopus.com/inward/record.url?scp=84864196086&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84864196086&partnerID=8YFLogxK

U2 - 10.1016/j.jacl.2012.01.009

DO - 10.1016/j.jacl.2012.01.009

M3 - Article

C2 - 22836071

AN - SCOPUS:84864196086

VL - 6

SP - 340

EP - 351

JO - Journal of Clinical Lipidology

JF - Journal of Clinical Lipidology

SN - 1933-2874

IS - 4

ER -