Statin-Associated Memory Loss: Analysis of 60 Case Reports and Review of the Literature

Leslie R. Wagstaff, Pharm.D., Melinda W. Mitton, Pharm.D., Beth McLendon Arvik, Pharm.D., P. Murali Doraiswamy, M.D.

Disclosures

Pharmacotherapy. 2003;23(7) 

In This Article

Methods

We searched the MedWatch data from November 1997-February 2002 for spontaneous adverse events of cognitive impairment associated with simvastatin, pravastatin, and atorvastatin. Simvastatin and pravastatin were selected based on the large amount of data supporting these agents in primary and secondary prevention of coronary events. Atorvastatin was chosen because of its large market share and because it is being studied for its antidementia benefits. Other statins, such as lovastatin, cerivastatin, and fluvastatin, were not included in our MedWatch search due to research time constraints.

Our request was submitted according to the Freedom of Information Act, and we were sent electronic files. The FDA as well as pharmaceutical companies have dedicated proprietary software for analyzing and conducting searches of adverse event reports. The dictionary used to code MedWatch adverse event terms is also proprietary; neither the software nor the dictionary was available to us.

Our initial searches were conducted on a personal computer using a word search, and we later reviewed selected reports manually. Approximately 25,000 adverse events (~13,500 with atorvastatin, ~ 8500 with simvastatin, ~3000 with pravastatin) were reported to MedWatch during this period. All three drug files were searched, using the following as preferred terms: memory, confusion, Alzheimer, think, cognition, attention, and mental. Using other search terms (e.g., those used by the FDA) may have yielded additional cases; however, we wished simply to identify a selection of representative cases rather than all of them. We chose those in which the statin was considered the primary suspect as the cause of mental status changes. About 2% of statin-associated adverse events had a cognitive identifier (cognitive, attentional, or amnestic disorder). The complete MedWatch reports were ordered from the FDA and were then reviewed to eliminate duplicates as well as adverse events that did not clearly involve memory loss or cognitive impairment. This resulted in 60 cognitive adverse events associated with pravastatin, simvastatin, and atorvastatin.

Documentation of statin type, reporter status, mean age, age range, sex, type of memory loss, time to memory loss, statin dosage, and effects of drug discontinuation and rechallenge were reviewed. Reporter status (person who submitted the report) was classified according to the checked box on the report form. As such, this was a descriptive study, and no statistical analyses were performed. Because individual MedWatch reports vary in completeness of demographics and clinical data provided, we have specified where such data were missing. Because reporters' names are deleted from MedWatch reports sent under the Freedom of Information Act, we could not contact the reporters to verify or clarify any information.

Using MEDLINE, we reviewed the published literature from January 1980-September 2002. Search terms used were HMG-CoA reductase inhibitors and statins, which were cross-referenced with each of the following terms: memory, brain, amnesia, cognition, mental, dementia, and Alzheimer's disease. We also used the prescribing information for atorvastatin, simvastatin, and pravastatin (dated April, May, and October 2002, respectively) as part of our review.

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