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08/24/2011 - monitoring liver tests in statin users

posted Sep 28, 2011, 5:22 PM by Chief Resident   [ updated Sep 28, 2011, 5:25 PM by Purnema Madahar ]
Hi everyone,

in the spirit of yesterday's less-is-more testing advise, an interesting question came up in clinic today: should we routinely check liver tests in patients on statins?

Official FDA recommendations on monitoring statin prescriptions call for liver tests on patients who started or increased the dose of a statin. These recommendations are however based on expert opinion and not supported by trial data.

A retrospective study in the Archives of liver tests in about 1000 patients on statins in a primary care practice found no significant elevation of ALT and AST related to statin use over the course of a year. The attached Lancet review on the safety of statins from 2007 looked at adverse outcomes in the many, large, statin trials and found only minor or non-significant numbers of patients on statins with elevated liver enzymes when compared to the control groups.

The Lancet paper also poses an important question: are elevations of liver enzymes really an indicator of liver injury or might they be a reflection of a hepatic reaction to the lowering of cholesterol levels? It does not answer this question, but concludes that the major statin trials do not indicate a significantly increased risk of liver damage from standard dose statins.

High dose statins seem to be different in this regard: both high dose atorvastatin and simvastatin have been associated with hepatotoxicity. The latter was implicated in the attached SEARCH trial, which compared simvastatin 80 mg versus 20mg in 12000 (!) participants with a history of MI and found 104 versus 30 participants with elevated liver enzymes, respectively. This lead the FDA to recently restrict the use of simvastatin 80 mg, see http://www.fda.gov/Drugs/DrugSafety/ucm256581.htm

Bottom line: in patients with no known liver disease who are not taking medications that potentiate levels of statins and who take standard dose statins, surveillance liver tests do not seem warranted.

To push the envelope even a little further, take a look at the attached post-hoc analysis of the GREACE trial, which looked at a subgroup of participants with abnormal liver tests who were randomized to statins or no statins and found that the group on statins actually had a reduction in liver enzyme elevation in the course of the study. The usual caveats for post-hoc analyses apply, but thought-provoking nonetheless.

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