HMG-CoA Reductase Inhibitors And Memory Loss

By: Yufan (Frank) Liu, Pharm.D. Candidate c/o 2013

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Results of numerous epidemiological studies have indicated that having high serum cholesterol can lead to coronary heart disease (CHD). ¹ More specifically having high LDL cholesterol puts patients at risk for angina and heart attack.² To reduce this risk HMG-CoA reductase inhibitors, also known as statins, have been developed to lower the incidence and progression of CHD. Multiple studies have found that statins reduce risk of major coronary events by about 30%.³ However every drug comes with risk of side effects, with statins being no exception. As a result, many health care professionals believe that LDL is an imperfect predictor of risk and that treating patients based on risk would be more appropriate.⁴ Therefore patients who wouldn’t need to be on a statin wouldn’t experience the side effects of the drug.

Initial reports have stated that the most dangerous side effect of statins was the occurrence of rhabdomyolysis, which results in the breakdown of muscle fibers which can damage the kidneys. Other side effects of statins include having gastrointestinal disturbances, fatigue, musculoskeletal pain, headache and hepatotoxicity.⁵ However, as more and more post marketing data became available, statins were also reportedly associated with the development of other side effects such as depression and diabetes.⁶ Most recently memory loss has also been an added adverse effect of these drugs.

In February of 2012, the FDA came out with a new warning that reversible memory impairment may occur in patients using statins. The FDA reported that the memory loss was reversible with resolution occurring approximately 3 weeks after discontinuation of the drug.⁷ The studies that were cited generally included subjects who were over 50 years of age. The onset of memory loss from the use of statins was highly variable ranging from one day to years after use. The studies stated that the cases do not appear to be associated with dementia or Alzheimer’s disease. The review also did not examine an association between memory loss and a specific statin, dose of statin, the age of the person or use of other medication.

Memory loss was never a new side effect for statins. According to the clinical trials conducted by Pfizer for atorvastatin (Lipitor^®), amnesia occurred in 7 out of 2502 of the subjects.⁸ Many case reports found that statin related memory loss involved simvastatin (Zocor^®) or atorvastatin (Lipitor^®) more commonly than other statins. In randomized control trials such as the heart study and the PROSPER study, which tested for reduced mortality by statins, no significant differences were found between patients receiving statins and the placebo group.^{9, 10}

There have been other studies that have tried to associate statins with cognitive impairment. One study tried to assess the cognitive function of patients who were taking lovastatin (Mevacor^®) 20 mg versus placebo at baseline and six months. After six months the patients who were on placebo improved on their test scores while the patients on lovastatin (Mevacor^®) actually regressed.¹¹ However, it wasn’t a significant regression and more studies are needed to make more definitive statements.

Statins are still very commonly prescribed drugs in the healthcare setting due to strong evidence that they decrease mortality. However, the FDA’s new release of safety labeling changes warrants a second look on assessing the risks and benefits of using these drugs. There have been several case reports associating statins with memory loss and a few randomized control trials associating statins with impaired cognition, but more studies should be done to understand the clinical significance of these case reports and studies.

SOURCES:

1. Mahley RW. “Atherogenic lipoproteins and coronary artery disease: concepts derived from recent advances in cellular and molecular biology.” Circulation. 1985; 72:943-8.
2. Ward S. “A systematic review and economic evaluation of statins for the prevention of coronary events” Health Technology Assessments. 4/2007; 11(14): 1-160.
3. LaRosa J “Effect of statins on the risk of coronary disease: a meta-analysis of randomized controlled trials”. JAMA. 1999; 282:2340-6
4. O’Riordan M “Treat risk and not LDL-cholesterol targets, new perspective argues” Medscape online. 1/2012
5. Crestor Package Insert. Wilmington, Delaware. Revised 2/2012
6. Morales K “Simvastatin causes changes in affective processes in adult volunteers”. Journal of American Geriatric Society. 2006; 54(1):70-76
7. “FDA drug safety communication: important safety label changes to cholesterol lowering statin drugs” Updated 3/5/2012. http://www.fda.gov/Drugs/DrugSafety/ucm293101.htm?utm_source=fda&utm_medium=website&utm_term=Statins&utm_content=p2&utm_campaign=P2#references
8. Pfizer, Inc. Data on file. New York, NY; 2002.
9. Shepherd J, Blauw GJ, Murphy MB, et al. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet 2002;360:1623-30.
10. Heart Protection Study Collaborative Group. MRC/BHF heart protection study of cholesterol lowering with simvastatin in 20,536 high-risk individuals: a randomized placebo-controlled trial. Lancet 2002;360:7-22.
11. Muldoon MF, Barger SD, Ryan CM, et al. Effects of lovastatin on cognitive function and psychological well-being. Am J Med. 2000;108:538-546.