Statins and liver enzyme testing: New FDA package labeling

I saw a woman in consultation for a prolactinoma responsive to cabergoline. I noticed, however, that she also had dyslipidemia. Her LDL cholesterol was 180 mg/dL. I suggested that she consider pharmacotherapy, as she had not responded to dietary and lifestyle modification.

The patient explained that she tried various statins in the past. Because of elevation of liver enzymes, however, she had been told by several other physicians that she must never be on a statin again. In their opinion it could be dangerous and damage her liver.

Her most recent alanine aminotransferase (ALT) was high at 185 U/L (7-45 U/L). However, all other liver studies, including aspartate aminotransferase (AST), gamma-glutamyltransferase (GGT), alkaline phosphatase and bilirubin, were all normal.

I explained to the patient that our understanding of the significance of elevated liver enzymes in patients on statins has evolved with time. In the past, many clinicians were concerned about the potential for hepatotoxicity in patients on statins.

However, in 2006 the National Lipid Association released a statement concluding that although elevated serum aminotransferases are common in patients on statin therapy, there is no evidence that it is an indication of statin-induced liver injury. They stated that elevated serum aminotransferases alone should not be a contraindication against statin therapy if it otherwise would be appropriate. They also suggested that the regulatory authorities reconsider the recommendations for routine monitoring of liver enzymes in patients on statins. I reviewed this issue previously in another post (http://www.endocrinetoday.com/comments.aspx?rid=82520#com ).

In February 2012, the FDA decided to remove the requirements for routine periodic monitoring of liver enzymes in patients on statins. The labels now advise that liver enzyme testing be performed before starting statin therapy as a baseline, and then only as clinically indicated afterwards.

The FDA agreed with the National Lipid Association’s previous conclusions that serious liver injury with statins is idiosyncratic, unpredictable and extremely rare. The FDA also noted that, despite the increasing use of statins since the late 1990s, there has not been an increase in the rates of fatal or severe liver injury cases related to statin use. Therefore, because routine monitoring of liver enzymes is not effective in detecting or preventing serious liver injury, it has been removed from the package labeling of all currently marketed statins.

In my consult note I sent back to the patient’s primary care physician, I very clearly explained why I was no longer concerned about isolated elevation of liver enzymes as long as there was not more objective evidence of liver injury (such as elevated bilirubin). This is what the peer-reviewed literature, the expert consensus guidelines, and now the FDA, tell us.

After I explained the potential risks/benefits of therapy (and also the potential risks of not treating her dyslipidemia), she agreed to try a statin again.

Unfortunately, however, new information spreads slowly. The patient called us shortly after her appointment with me. Apparently after discovering that I had started this patient on a statin, she told us that her primary care physician “was not happy.”

What did I do?

After first reassuring the patient that we will be monitoring closely, I prepared a letter to be sent to her primary care physician. My very detailed explanation in my consult apparently was not sufficient in fully explaining my position, therefore I also included copies of the 2006 National Lipid Association statement along with the more recent FDA communication regarding changes to statin package labels.

How will her primary care physician respond? I do not know.

Most unfortunately, recommendations are often made to patients that are not always based on the current scientific evidence or expert consensus guidelines. This results in some patients not receiving potentially life-saving therapy.

I try to be as tactful as I can when dealing with colleagues who are uninformed or not up-to-date. Most are extremely appreciative for my input. Regrettably, there occasionally are others who decline to listen to anything I, or anyone else, may say.

For more information:

Cohen DE. Am J Cardiol. 2006;97:77C-81C.

FDA Drug Safety Communication: Important safety label changes to cholesterol-lowering statin drugs 2/28/2012 http://www.fda.gov/Drugs/DrugSafety/ucm293101.htm