Why Statins Don't Work Well in 1 in 5 Users

Certain gene mutations may reduce the drugs' effectiveness.

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Often hailed as "wonder drugs" for their ability to lower cholesterol and reduce heart attack risk, statins actually don't work that well in about 20 percent of users. Turns out, these people may have certain genetic mutations that lower the drugs' effectiveness, according to a new study from Duke University Medical Center. Those who carry a specific mutation in the ABCA1 gene, which is responsible for cholesterol transport into and out of cells, had a 24 percent decline in their "bad" LDL cholesterol levels after going on a low-dose statin compared with a 32 percent reduction in those who didn't carry the gene mutation.

These folks might need to switch to a more powerful statin, study author Deepak Voora tells me. Or perhaps they might want to try combining a statin with a cholesterol-lowering fibrate drug. A new one, called TriLipix, was approved yesterday.

I asked Voora to tell me a little more about how statin users and their physicians should apply this new finding. Here are some edited excerpts of our conversation:

Is a genetic test available to identify this mutation?


Not yet. And our findings need to be replicated before we know for certain that the link is actually real. What should people do if their statin doesn't get their cholesterol down to a healthy level?


If they're taking a less powerful statin, like Pravachol or Zocor, they would probably benefit from switching to a more powerful drug like Crestor or Lipitor. Our study suggests they wouldn't benefit as much from taking a higher dose of a weaker statin. In fact, a higher dose would increase the possibility of common side effects like severe muscle pain, achiness, and cramps. Higher doses could also increase those rare complications like muscle inflammation (myositis) and muscle tissue death (rhabdomyolysis). So if I'm finding that a 10-milligram dose of Pravachol isn't getting my LDL levels down enough, I would be better off switching to 10 mg of Crestor instead of 20 mg of Pravachol?


Essentially yes, though the doses don't translate exactly from statin to statin. You can also talk to your doctor about adding a fibrate like Lopid or TriLipix; these are good at lowering high triglycerides, lipids that are also associated with increased heart disease risk. Clinical trials of TriLipix indicated that the drug when used in combination with a statin helped people control LDL levels better than the use of a statin alone. Just how much fibrates help, though, still isn't clear. A more definitive study, whose results are expected in 2010, should provide more answers on this. Here are seven reasons why you shouldn't dismiss statin pain and what to do if you have mildly elevated cholesterol.