FDA Statin Label Update Commentary

National Lipid Association Statement on FDA Statin Label Changes Posted March 1 2012

On February 28, 2012, the Food and Drug Administration (FDA) approved crucial changes to the safety label for statins. The changes are based upon the FDA's further review of the data and are as follows:

Removing the recommendation for periodic monitoring of liver enzymes;

Adding a warning regarding the potential and non-life threatening side effect of memory loss; and
Adding a warning about the potential for increased blood sugar and hemoglobin (HbA1c) levels.
The complete safety announcement from the FDA can be viewed here:
http://www.fda.gov/Drugs/DrugSafety/ucm293101.htm

These label changes will be applied to Lipitor (atorvastatin), Lescol (fluvastatin), Mevacor (lovastatin), Altoprev (lovastatin extended-release), Livalo (pitavastatin), Pravachol (pravastatin), Crestor (rosuvastatin), and Zocor (simvastatin).

The FDA is also updating the label of lovastatin to reflect drug interactions. These interactions may increase the risk of myopathy/rhabdomyolysis when taken with protease inhibitors. Furthermore, the FDA change indicates that lovastatin should not be used with gemfibrozil instead of the 20 mg dosage limitation in the former package insert (PI). See the table regarding recommendations at the following link.
http://www.fda.gov/Drugs/DrugSafety/ucm293101.htm#dose

The National Lipid Association (NLA) applauds the FDA’s decision to remove the need for periodic liver enzyme testing of patients on statin therapy. According to the new labels, the FDA recommends that such tests be conducted before starting therapy and as indicated thereafter. According to an FDA press release issued on February 28, "The FDA has concluded that serious liver injury with statins is rare and unpredictable in individual patients, and that routine periodic monitoring of liver enzymes does not appear to be effective in detecting or preventing serious liver injury."1 The NLA's Statin Safety Task Force reached this same conclusion and their recommendation was cited by the FDA as a reason for the labeling change. To read the complete report from the NLA click here [http://www.lipid.org/pdfs/Statin_Safety_Task_Force.pdf].

As the FDA quotes in their communication "There have been rare post-marketing reports of cognitive impairment (e.g., memory loss, forgetfulness, amnesia, memory impairment, confusion) associated with statin use. These reported symptoms are generally not serious and reversible upon statin discontinuation, with variable times to symptom onset (1 day to years) and symptom resolution (median of 3 weeks)." The FDA communication further reports " Data from the observational studies and clinical trials did not suggest that cognitive changes associated with statin use are common or lead to clinically significant cognitive decline." Similarly the 2006 NLA expert paper on statin safety2 addressed raised anxieties on the potential reports regarding cognition but investigators were unable to conclusively establish the clinical relevance or pathologic mechanism of these outcomes. Ultimately, the NLA believes further analysis of any cognitive connection needs to be researched.

According to the FDA's interpretation of the data and literature, patients on statin therapy may have increased blood sugar and glycosylated hemoglobin (HbA1c) levels. These findings are based upon a review of the literature and the JUPITER trial, in which high-dose statins resulted in worsening glycemic control. However, the NLA emphasizes that, in most cases, the risk of new onset diabetes is low and supports the FDA's conclusion that the cardiovascular benefits of statins outweigh these small increased risks.

Recommendations for Clinicians
Physicians should not alter their prescribing patterns. The risk-benefit ratio supports the use of statin therapy in combination with lifestyle modification to prevent cardiovascular events, as the benefits of statins continue to outweigh any associated risks. Liver enzyme testing should occur prior to initiating therapy and thereafter as clinically indicated.

The NLA further agrees with the FDA's belief that the cardiovascular benefits of statins outweigh the small increased risk associated with increases in glucose and Hemoglobin A1c. We recommend that statin therapy should not be discontinued because of this.

Recommendations for Patients
Statins continue to be highly effective at lowering cholesterol levels, therefore preventing cardiovascular events. Patients should not discontinue statin therapy without the advice of their healthcare providers. It is extremely important for patients to achieve the cholesterol level goals set by their physicians. When meeting with their healthcare providers, patients should discuss all options for managing their cholesterol, including lifestyle modification.

References:

"FDA Drug Safety Communication: Important Safety Label Changes to Cholesterol-Lowering Statin Drugs." Press Release. Accessed February 28, 2012, online at http://www.fda.gov/Drugs/DrugSafety/ucm293101.htm

"Report of the National Lipid Association's Statin Safety Task Force." American Journal of Cardiology. April 17, 2006. VOL 97 (8A). Available online at http://www.lipid.org/pdfs/Statin_Safety_Task_Force.pdf

The NLA contributors to this paper have provided full disclosures and their thoughts on this matter have not been influenced by bias or commercial interest. The viewpoints expressed here represent the clinical experience and opinion of our experts and the scientific evidence, which serves as the basis of clinical lipidology. All members of the organization and others reviewing this document are urged to thoroughly review the study and place this, in addition to other learned comment, in the context of meeting the interests of patient care. The NLA further discloses that the association has received educational grants from multiple manufacturers to support accredited medical educational activities. There was no funding or any interaction with any manufacturer in regard to this statement.