Can a Drug That Helps Hearts
Be Harmful to the Brain?

February 12, 2008; Page D1

Cognitive side effects like memory loss and fuzzy thinking aren’t listed on the patient information sheet for Lipitor, the popular cholesterol-lowering drug. But some doctors are voicing concerns that in a small portion of patients, statins like Lipitor may be helping hearts but hurting minds.

SIDE EFFECTS OF STATINS

• Like every medication, statins also have side effects such as muscle aches and memory loss that can be difficult to measure.

“This drug makes women stupid,” Orli Etingin, vice chairman of medicine at New York Presbyterian Hospital, declared at a recent luncheon discussion sponsored by Project A.L.S. to raise awareness of gender issues and the brain. Dr. Etingin, who is also founder and director of the Iris Cantor Women’s Health Center in New York, told of a typical patient in her 40s, unable to concentrate or recall words. Tests found nothing amiss, but when the woman stopped taking Lipitor, the symptoms vanished. When she resumed taking Lipitor, they returned.

“I’ve seen this in maybe two dozen patients,” Dr. Etingin said later, adding that they did better on other statins. “This is just observational, of course. We really need more studies, particularly on cognitive effects and women.”

Pfizer Inc.’s Lipitor is the world’s best-selling medicine, with revenues of $12.6 billion in 2007. The company says that its safety and efficacy have been demonstrated in more than 400 clinical trials and 145 million patient years of experience, and that the extensive data “do not establish a causal link between Lipitor and memory loss.” Pfizer also says it draws conclusions about adverse events from a variety of sources “as opposed to anecdotal inferences by individual providers with a limited data pool.”

World-wide, some 25 million people take statins, including Zocor, Mevacor, Crestor, Pravachol and Vytorin. As a group, they are widely credited with reducing heart attacks and strokes in people at high risk, though the benefits are less clear in people who are not at high risk, particularly women and the elderly. Some 15% of patients complain of side effects; muscle aches and liver toxicity are the most recognized to date. But anecdotes linking statins to memory problems have been rampant for years.

On balance, most cardiologists see little cause for concern. “The benefits far outweigh the risks,” says Antonio Gotto, dean of the Weill-Cornell Medical School and past president of the American Heart Association. Dr. Gotto, who has consulted for most of the statin makers and been involved in many of the trials, says “I would hate to see people frightened off taking statins because they think it’s going to cause memory loss.”

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Thinking and memory problems are difficult to quantify, and easy for doctors to dismiss. Many people who take statins are elderly and have other conditions and medications that could have cognitive side effects.

Still, the chronology can be very telling, says Gayatri Devi, an associate professor of neurology and psychiatry at New York University School of Medicine, who says she’s seen at least six patients whose memory problems were traceable to statins in 12 years of practice. “The changes started to occur within six weeks of starting the statin, and the cognitive abilities returned very quickly when they went off,” says Dr. Devi. “It’s just a handful of patients, but for them, it made a huge difference.”

Researchers at the University of California at San Diego are nearing completion of a randomized controlled trial examining the effects of statins on thinking, mood, behavior, and quality of life. Separately, the UCSD researchers are collecting anecdotal experiences of patients, good and bad, on statins; memory problems are the second most common side effect, after muscle aches, in about 5,000 reports to date.

“We have some compelling cases,” says Beatrice Golomb, the study’s lead researcher. In one of them, a San Diego woman, Jane Brunzie, was so forgetful that her daughter was investigating Alzheimer’s care for her and refused to let her babysit for her 9-year-old granddaughter. Then the mother stopped taking a statin. “Literally, within eight days, I was back to normal — it was that dramatic,” says Mrs. Brunzie, 69 years old.

Doctors put her on different statins three more times. “They’d say, ‘Here, try these samples.’ Doctors don’t want to give up on it,” she says. “Within a few days of starting another one, I’d start losing my words again,” says Mrs. Brunzie, who has gone back to volunteering at the local elementary school she loves and is trying to bring her cholesterol down with dietary changes instead.

“I feel very blessed — I got about 99% of my memory back,” she adds. “But I worry about people like me who are starting to lose their words who may think they have just normal aging and it may not be.”

Of course, not every case of mental decline can be reversed by stopping statins. In fact, there’s some evidence that statins may ward off Alzheimer’s by reducing plaque and inflammation in the brain.

DRUG RESEARCH

Learn more at these sites:

• The University of California-San Diego Statin Effects Study: www.statineffects.com

• The University of California-San Diego Statin Effects Study: www.fda.gov/medwatch

• Drug information from health-care organizations. The FDA’s Adverse Event reporting program: www.nlm.nih.gov/medlineplus/druginformation.html

On the other hand, the brain is largely cholesterol, much of it in the myelin sheaths that insulate nerve cells and in the synapses that transmit nerve impulses. Lowering cholesterol could slow the connections that facilitate thought and memory. Statins may also lead to the formation of abnormal proteins seen in the brains of Alzheimer’s patients.

The cognitive changes can affect men as well as women. But women on statins are often simultaneously losing estrogen due to menopause, which can also cause cognitive changes. “Women are getting hit with a double whammy,” says Elizabeth Lee Vliet, a women’s health physician in Tucson, Ariz., who has a background in neuroendochronology.

Side effects are always highly individual. Most patients tolerate statins very well, and heart disease remains the leading cause of death in the U.S. for men and women.

But it pays to think hard about whether you really need to be on a statin — or if you could accomplish your goals with diet and exercise instead. “Some people want to take a pill and think they can eat whatever they want,” says Nieca Goldberg, a cardiologist and medical director of the Women’s Heart Program at the New York University School of Medicine. She says she typically prescribes statins for women who have elevated cholesterol and have already had a heart attack. But for younger women with high cholesterol and no other risk factors, she encourages lifestyle changes.

“I try to initiate diet modifications and physical activity in all my patients — even if they still need medication, I can give them a lower dose,” says Dr. Goldberg. “I try to make the point that we are all in this together.”

If you do need to be on cholesterol-lowering medication, pay close attention to any side effects and talk with your doctor. You may have a different experience with a different dose or different statin. Also remember that the doctor taking care of your heart condition may not be as experienced in other body parts. “You really need a balanced approach,” says Dr. Vliet. But “each physician may be looking at only one part of the elephant — that’s the way medicine is practiced in the U.S.

As Jane Brunzie says, “I learned through this experience that you have to use your own brain, as well as your doctor’s brain, when it comes to your health.”

CORRECTIONS & AMPLIFICATIONS: Pfizer Inc. says that the extensive clinical trial data on its best-selling cholesterol drug Lipitor “do not establish a causal link between Lipitor and memory loss.” An earlier version of this Health Journal column misspelled causal as casual.

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