New Warning for Statins

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Statins, including Pfizer Inc.’s Lipitor, are among the most prescribed drug in the world, and are currently routinely taken by millions of Americans. They are indicated for people with high blood pressure and/or high cholesterol, and have been shown to significantly reduce the risk of heart disease, heart attack, and stroke in this population. Yet the FDA has just issued new warnings concerning potential side effects: elevated blood sugar, which is a risk factor for developing type 2 diabetes, and cognitive impairment such as memory loss. The warnings will not be affixed to the outside of the bottle, but will be included in the package insert that comes with all prescription medications.

The FDA constantly monitors the medical literature and clinical trial data to keep abreast of newly reported side effects of approved drugs. Recent studies of Crestor, a statin made by AstraZeneca, revealed that it was associated with an elevated risk of developing type 2 diabetes. Memory loss has not been associated with statin use in any formal study, but comes from many anecdotal reports. People taking statins have been complaining of “fuzzy” thinking and their inability to recall words; both of these disappeared once they went off of the drug. Doctors often disregarded this complaint in their patients as a normal part of aging, but the FDA wanted people to be aware of the potential correlation.

Doctors can also belittle complaints of muscle pain in older patients. But many of these patients are taking multiple prescription drugs, and statins have in fact been shown to increase the risk of muscle injury in combination with some other drugs. Lovastatin’s new warning label clarifies this risk as well, listing which drugs should be avoided if one is taking it and noting the maximal dose of Lovastatin if these combinations cannot be avoided.

Interestingly, a warning that has been affixed to statins to date is now being removed, this one for the periodic monitoring of liver enzymes. It was there because early clinical trials suggested that statin use could lead to liver damage. Cholesterol is formed in the liver, so that is where statins do their work. But this liver damage is quite rare, and monitoring liver enzymes could not predict who might develop it or in any way prevent it. Perhaps blood sugar, levels should now be monitored instead.

Statins still clearly have enormous benefits; they are very good at lowering cholesterol, and thereby lowering the risk of heart attack and stroke. They continue to be invaluable for those at high risk of cardiovascular disease, such as those with genetic high cholesterol. Amy G. Egan, M.D., M.P.H., the deputy director for safety in the FDA’s Division of Metabolism and Endocrinology Products, put it like this [1]:

Their benefit is indisputable, but they need to be taken with care and knowledge of their side effects.

New drugs that have fewer side effects and are potentially more effective than statins are on the way. A recent study published in The New England Journal of Medicine evaluated a new drug called REGN727, a monoclonal antibody that blocks the action of a protein that helps to limit the amount of low-density lipoprotein (LDL), or bad cholesterol, that liver cells can remove from the bloodstream [2]. By blocking the inhibiting protein, liver cells can remove much greater amounts of LDL from the body. Indeed, the results of unpublished studies show that REGN727 in patients already taking Lipitor can reduce LDL by an additional 40-70% compared with those on a placebo [3].

References

1. FDA Expands Advice on Statin Risks. U.S. Food and Drug Administration Consumer Update. 2012 Feb 29.
2. Stein et al. Effect of a monoclonal antibody to PCSK9 on LDL cholesterol. N Engl J Med. 2012 Mar 22;366(12):1108-18.
   View abstract
3. Drug to Cut Cholesterol Tests Better Than Statin. The New York Times. 2012 Mar 26.