Are Liver Tests Now “Irrelevant” When Prescribing Statins?
I have been consistently flabbergasted when I hear that angiotensin-converting enzyme (ACE) inhibitors are contraindicated in persons with renal disease. Yes, ACE inhibitors should be used with caution in patients with acute renal injury and high-grade renal vascular lesions, but these drugs are designed to help, not hurt kidneys. Now fast forward to another caveat: avoid or discontinue statins in patients who have elevated liver enzyme levels. Get ready for a therapeutic paradigm shift.
GREEK STUDY RESULTS CHALLENGE ACCEPTED PRACTICE
The GREACE (Greek Atorvastatin and Coronary Heart Disease Evaluation) Study randomized patients with coronary vascular disease to statin therapy or “usual” care.1 A post hoc analysis looked at risk reduction for recurrent cardiovascular events specifically in patients treated with a statin who had a transaminase level (either aspartate aminotransferase or alanine aminotransferase [ALT]) less than 3 times the upper limit of normal. In 437 patients with moderately abnormal liver test results, 227 who received a statin actually had improved results, while 210 who were not treated with a statin experienced an increase in liver enzyme levels. Not only did liver enzyme levels decrease in the statin group, but these patients also had a 68% relative risk reduction for cardiovascular events.
Note that the relative risk reduction was greater in patients with elevated liver enzyme levels. It appears that the improvements in liver enzyme levels and cardio vascular risk result from amelioration of underlying nonalcoholic fatty liver disease, a disease with an incidence of 20% in developed countries.2
STATINS MAY HELP, NOT HURT THE LIVER
The editorialist Ted Bader, MD, was frank: “Statininduced hepatotoxicity is a myth.”2 He referenced 2 studies that he performed in which patients with hepatitis C who took statins also had reductions in liver enzyme levels.3,4 Thus, one of the pleiotropic effects of statins appears to be a decrease in viral replication in hepatitis C virus infections. Bader2 emphasized that increased ALT levels in persons in the clinical setting studied by the GREACE investigators do not represent a statin-induced liver disease, but rather a disease mitigated by statins.
There is work to do. Bader2 also noted that 50% of academic physicians would be reluctant to prescribe a statin for a patient with an ALT level more than 1.5 times the upper limit of normal. More than 40% would avoid a statin in patients with chronic hepatitis C.
Yes, these studies and commentary represent a therapeutic paradigm shift. Statins are not hepatotoxins. They are not contraindicated in persons with moderate elevations in liver enzyme levels. In fact, they mitigate liver injury from insulin resistance and hepatitis C, and they also protect against cardiovascular events.
1. Athyros VG, Tziomalos K, Gossios TD, et al; GREACE Study Collaborative Group. Safety and efficacy of long-term statin treatment for cardiovascular events in patients with coronary heart disease and abnormal liver tests in the Greek Atorvastatin and Coronary Heart Disease Evaluation (GREACE) Study: a post hoc analysis. Lancet. 2010;376:1916-1922.
2. Bader T. Liver tests are irrelevant when prescribing statins. Lancet. 2010;376: 1882-1883.
3. Bader T, Fazili J, Madhoun M, et al. Fluvastatin inhibits hepatitis C replication in humans. Am J Gastroenterol. 2008;103:1383-1389.
4. Madhoun MF, Bader T. Statins improve ALT values in chronic hepatitis C patients with abnormal values. Dig Dis Sci. 2010;55:870-871.