Effect of intensive lipid lowering with atorvastatin on cardiovascular outcomes in coronary heart disease patients with mild-to-moderate baseline elevations in alanine aminotransferase levels

被引:161
作者
Tikkanen, Matti J. [1 ,2 ]
Fayyad, Rana [3 ]
Faergeman, Ole [4 ]
Olsson, Anders G. [5 ,6 ]
Wun, Chuan-Chuan [3 ]
Laskey, Rachel [3 ]
Kastelein, John J. [7 ]
Holme, Ingar [8 ]
Pedersen, Terje R. [8 ,9 ]
机构
[1] Univ Helsinki, Cent Hosp, Div Cardiol, Dept Med, FIN-00290 Helsinki, Finland
[2] Folkhalsan Res Ctr, Helsinki, Finland
[3] Pfizer Inc, New York, NY USA
[4] Arhus Univ Hosp, Dept Cardiol B, Aarhus, Denmark
[5] Linkoping Univ Hosp, Fac Hlth Sci, Dept Internal Med, S-58185 Linkoping, Sweden
[6] Stockholm Heart Ctr, Stockholm, Sweden
[7] Univ Amsterdam, Acad Med Ctr, Dept Vasc Med, NL-1105 AZ Amsterdam, Netherlands
[8] Oslo Univ Hosp, Ctr Prevent Med, Oslo, Norway
[9] Univ Oslo, Oslo, Norway
关键词
Coronary heart disease; Statins; Cardiovascular risk; Liver enzymes; Alanine aminotransferase; Fatty liver disease; DENSITY-LIPOPROTEIN CHOLESTEROL; FATTY LIVER-DISEASE; GREEK ATORVASTATIN; EVENTS; SIMVASTATIN; ABSORPTION; PREVENTION; GUIDELINES; MARKERS; SAFETY;
D O I
10.1016/j.ijcard.2013.06.024
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Background: Statins may reduce cardiovascular (CV) morbidity in patients with mild-to-moderate elevations in liver enzyme levels. This post-hoc analysis of the IDEAL study compared intensive versus moderate statin therapy for the prevention of CV events in coronary heart disease patients with normal and elevated baseline levels of serum alanine aminotransferase (ALT). Methods: Cox regression analysis was used to investigate the effect of atorvastatin 80 mg/day versus simvastatin 20-40 mg/day on the risk of IDEAL study end points in patients with normal baseline ALT (defined as ALT < ULN [upper limit of normal]) versus elevated baseline ALT (ALT >= ULN). Results: Of 8863 IDEAL patients with non-missing baseline ALT values, 7782 (87.8%) had an ALT < ULN and 1081 (12.2%) had an ALT >= ULN. In patients with elevated baseline ALT, major CV event rates were 11.5% for simvastatin and 6.5% for atorvastatin, indicating a significant risk reduction with intensive statin therapy (hazard ratio, 0.556; 95% confidence interval, 0.367-0.842; p = 0.0056). Significant heterogeneity of treatment effect was observed for major CV events, cerebrovascular events, and major coronary events, with a trend towards treatment difference for the other outcomes, indicating a greater benefit with atorvastatin in the elevated ALT group. Conclusions: The CV benefit of intensive lipid lowering with atorvastatin compared with a more moderate regimen with simvastatin was generally greater in patients with mildly-to-moderately elevated baseline ALT than patients with normal baseline ALT. Moderate elevations in liver enzyme levels should not present a barrier to prescribing statins, even at higher doses, in high-risk patients. (C) 2013 Elsevier Ireland Ltd. All rights reserved.
引用
收藏
页码:3846 / 3852
页数:7
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