Wednesday, July 11, 2007

Statins Implicated in Nerve Disease

The following is not a result of a clinical trial - yet. It's not getting much attention from the medical community. But if you're considering taking a statin (Crestor, Lipitor, Zocor, Vytorin, etc.) to manage your cholesterol, you may find this story of interest.

Last Tuesday, July 3rd, the Wall Street Journal ran a front-page story about statins and their link to amyotrophic lateral sclerosis (ALS), also known as Lou Gehrig's disease:

A Risk in Cholesterol Drugs Is Detected, but Is It Real?

The story was based on an interview with Dr. Ralph Edwards, director of the World Health Organization's drug monitoring center, and on a paper he and his colleagues published in the journal Drug Safety last month.1

Dr. Edwards sifts through reports of adverse events experienced by consumers of a drug after that drug has gone to market - millions of reports. Last year, he noticed something:
"Of 172 people in his database who developed Lou Gehrig's disease or something similar while taking prescription medicines, 40 had been on statins."
- WSJ story
"Of a total of 5534 safety reports of peripheral neuropathy, 547 were on statins."
- Drug Safety study
Even the FDA noticed a statin-ALS link - half a year before Dr. Edwards and using a different data base:
"The FDA says that through the end of last year, about one-third of the ALS adverse-event reports in its database - 99 of 298 - involved people on statins."
- WSJ Story
Many people who take statins experience muscle pain or weakness. I've seen studies recently that link statin use to reversible peripheral neuropathy - numbness, tingling, burning in hands or feet that goes away when the drug is stopped. However, that a statin might be linked to development of an irreversible degenerative nerve disease such as Lou Gehrig's or other ALS-like disorder is troubling.

Why A Statin-ALS Link Isn't Getting Much Attention

One reason this study isn't getting much attention is that it's a result of data-mining, not of a controlled clinical trial - the gold standard of research. In a clinical trial, adverse events that occur in the people taking the drug can be compared to a fairly similar group of people not taking the drug, which increases the belief that the drug is causing the problem.

Also, participants of a clinical trial are well screened, so that confounders can either be eliminated up front (via exclusion criteria) or adjusted statistically. For example, what if many of the people taking a statin who developed ALS were also smokers? Could smoking, and not statin-taking, be the real cause of the adverse event? In this case, smoking is considered to be a confounder, and in a clinical trial, can be taken into account.

Another reason it's not getting much attention is that ALS is rare (for now), while heart disease (the disease statins are most often used to treat) is not. However, it is exactly because it is rare that it is unlikely to show up in a clinical trial. As Dr. Edwards points out, "[The trials are] relatively short term. Because ALS is a progressive disease, its onset might be rather slow."

So even though cases that arise via data-mining can be complicated by confounders, the technology is useful in detecting problems that take a while to develop (since it's employed after-market). And in the case of a less common disease, data-mining can pick up vagaries where a clinical trial is hampered by its smaller population size.

A third reason might be that as the second most prescribed drug in the US (antidepressants top them), statins serve to generate enormous profits for their manufacturers. There were 203 million prescriptions written for them in 2006, at a cost to consumers of $16.5 billion.2 Statins are also very good at what they do, reducing cholesterol.

The lesson I take away from this is that it's foolish not to employ lifestyle changes to reduce cholesterol - changes that have been documented to work - before going the statin route.3 Not only will they save you money (statins are a long-term and expensive therapy), but they provide advantages that statins don't.

See my next post, How To Avoid Filling A Statin Prescription, for four lifestyle changes that can help manage cholesterol and reduce risk for heart disease.
1 Statins, Neuromuscular Degenerative Disease And An Amyotrophic Lateral Sclerosis-Like Syndrome: An Analysis Of Individual Case Safety Reports From Vigibase
2 The Statin Drugs, Prescription and Price Trends, Consumers Union, February 2007, and IMS Health Inc.
3 It's important to consult with your physician before halting or foregoing statin therapy. As Eric noted in comments, not all cases of high cholesterol respond to lifestyle measures.

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