Wednesday, July 07, 2004
For six months, Judy Shankland has had a little more spring in her step. The multiple sclerosis she has coped with for 17 years is not as draining. She has a little more energy, she's stronger, she can walk a distance without getting so tired.
The retired schoolteacher has been taking one of the leading MS drugs for years. In January, she added atorvastatin, a drug not known for MS treatment — but along with other "statins" widely recognized for its ability to lower cholesterol.
Like scores of scientists, she wonders if the drug really is making the difference in how she feels.
"Whether it's cause and effect, I don't know ... but it makes sense it would work," said Shankland, 64, a Freeport, Ill., resident whose University of Wisconsin physician prescribed the medication for her.
Widely hailed for lowering the risk of heart attacks and strokes by 25 to 35 percent, statins are gaining enhanced status.
A spate of recent studies have suggested the drugs may lower the risk of a variety of other diseases. Some promoters are calling them the "new aspirin." Drug companies have petitioned the Food and Drug Administration to allow them to be sold over the counter for heart disease.
Alzheimer's disease. Multiple sclerosis. Prostate cancer. Breast cancer. Glaucoma. Rheumatoid arthritis. Osteoporosis. All have been analyzed in patients taking statins for cardiovascular disease.
Scientists are intrigued with the research. But they are far from ready to start regularly prescribing the medications for any of the additional medical problems.
"Not to say the studies aren't true, but they haven't really proved many things," said Dr. Greg Brown, a University of Washington cardiologist, who in the late 1980s directed the first major study showing statins' cardiovascular benefits. "The studies have all had small numbers of patients."
More study needed
No one knows for sure why statins seem to have a protective effect on the conditions beyond cardiovascular disease. Researchers suspect their ability to reduce inflammation may at the root of it.
"I think the growing information we have about the utility of statins ... warrants additional study. They may affect disease processes," said Dr. Bryan Brewer, chief of the molecular-disease branch of the federal National Heart, Lung and Blood Institute.
Scientists say "prospective" clinical trials — the gold standard of drug tests — are sorely needed to prove statins protect against each disease.
In such trials, a large number of patients, often thousands, are given a drug; a comparable number are given a placebo; and no one knows who got which pill. After a specified time, researchers open records to learn who received the drug. The two groups of patients are compared to determine who ended up with the disease, or whose condition improved.
So far, most of the studies suggesting statins' additional protection have been small and "observational." That is, researchers analyzed the medical records of patients who took the drugs for cholesterol lowering and compared their medical histories with an equal number of patients who did not take statins. Or the studies have been in laboratory animals.
Multiple sclerosis, which affects about 400,000 patients in the U.S. alone, is one of the diseases most recently targeted by scientists.
A study at several medical centers found that the brain lesions of 30 MS patients treated with simvastatin decreased by an average 44 percent. That has led to some physicians prescribing statins for patients such as Shankland, even though they are not specifically approved for MS by the FDA. The practice is legal, and statins generally have been proved safe.
Shankland briefly tried two other statins, which caused flulike symptoms, before settling on atorvastatin for her MS. Now she's hopeful the drug really is helping her and that it will have a long-term effect.
"I have a good attitude about it," she said. "From all I read, it could be a good drug for MS. ... Maybe the next study will tell us."
The next study is just beginning. Led by Dr. Scott Zamvil, of the University of California, San Francisco, it will be the first to compare a statin, atorvastatin, with a placebo. The research involves 152 patients at 15 medical centers, including Virginia Mason Medical Center. It will address whether the drug could prevent the full onset of MS in patients who have had one attack of the disease.
"I'm optimistic we'll find useful results and benefits from the statin," said Zamvil, whose earlier research found the drug prevented progression of the disease in mice experiencing an initial attack.
While MS has been prominent in news of statins lately, scientists also are fascinated by other early studies that have suggested statins' beneficial effects. These include:
Alzheimer's disease: Affecting more than 4 million people in the United States, Alzheimer's has been the focus of dozens of studies in recent years — some showing a risk reduction with statins. The research is a prime example of why still more investigation is required.
Many scientists believe elevated cholesterol is involved in the production beta amyloid, which, in one form, makes up the plaque clogging the brains of Alzheimer's patients.
But studies showing that statins lower the risk of Alzheimer's have been in patients who already have cardiovascular disease — which in itself can lead to dementia. Thus statins' proven impact on cardiovascular disease may be the real reason for decreasing Alzheimer's risk.
And some studies have shown that statins do not decrease the amount of beta amyloid in the blood.
"Basically, there is a lot we don't know yet. We need to learn more before jumping to say everyone should be on statins to protect against Alzheimer's," said Dr. Edward Zamrini, of the University of Alabama at Birmingham.
Zamrini led an observational study that found a 39 percent reduction in the risk of Alzheimer's in Veterans Affairs Hospital patients taking statins who also had vascular disease of the heart or brain or high blood pressure.
A prospective trial involving about 400 people is now under way at 40 medical centers nationwide, including the UW Alzheimer's Disease Research Center at the Veterans Affairs Medical Center in Seattle. The study will last until mid-2006.
Prostate cancer: In a study of 430 veterans' medical records, Oregon Health & Science University researchers found a 58 percent lower risk of the cancer in men who have taken statins than in men who have not. Other studies in laboratories have suggested that statins both slow tumor-cell growth and induce their death.
Dr. Jackilen Shannon, lead author of the OHSU study, said of her research: "While these data are suggestive, this is a pilot study limited by small sample size and lack of control for additional [disease] factors. Further investigation is warranted."
Breast cancer: Older women who take statins for at least five years may reduce their risk of breast cancer as much as 30 percent, according to researchers at the Fred Hutchinson Cancer Research Center, Group Health Cooperative Center for Health Studies and the UW. The scientists analyzed the records of 975 women, ages 65 to 79, and compared them with the records of 1,007 women of the same ages without the disease.
Dr. Denise Boudreau, of the Center for Health Studies and lead investigator in the study, recently received additional funding from the National Cancer Institute to further investigate. "Clearly, the effects of statins on cancer are not completely understood," said Boudreau and her colleagues.
Rheumatoid arthritis: Scientists at the University of Glasgow, Scotland, reported that patients who took atorvastatin had a "modest" decrease in inflammation stemming from arthritis, compared with patients given placebos.
The 116 patients in the study were assessed for disease severity, including pain and the number of swollen joints. Earlier research with simvastatin had shown the anti-inflammatory effect in laboratory mice.
Glaucoma: Men age 50 and older who took statins had a 40 percent lower risk of glaucoma than those who did not take the drug, according to research published in June by University of Alabama at Birmingham scientists.
The medical records of 667 men with glaucoma were compared with the records of 6,667 who did not have the disease. A similar risk reduction was also found in men who took other, nonstatin cholesterol-lowering drugs. "Additional investigation is warranted," the researchers said.
Osteoporosis: Some small studies have shown that statins increase bone density in post-menopausal women, while other studies have shown no effect. Increased bone density decreases the risk of fractures. Additional studies are needed to determine whether statins really do stimulate bone formation, scientists say.
Heart benefits proved
While the potential new uses of statins clearly need more investigation, their benefits for patients with cardiovascular disease have been well established in the 15 years since their introduction.
They lower harmful cholesterol called LDL (low density lipoproteins), which contributes to buildup of plaque on artery walls. They help reduce the plaque itself. And they reduce inflammation in the arteries, which, in turn, stabilizes plaque, preventing it from breaking off and causing a heart attack.
"I think they're OK drugs, good drugs ... but my perspective is they're not miracle drugs," said Brown of the UW.
More than 13 million people in the U.S. take a statin, but experts say as many as 36 million need one of the drugs to lower heart-attack risk. Sales worldwide were nearly $12.5 billion in 2003. Some in the industry already have pushed for over-the-counter sales of the drugs.
The FDA in 2000 rejected two companies' applications for OTC sales of their statins, saying patients need regular physician monitoring. The drugs can cause liver and muscle problems if not taken properly.
Now, as many of the drugs approach the expiration of their patents, some companies are renewing their OTC efforts in the U.S. United Kingdom health officials recently approved the nonprescription sales. But monitoring remains a concern by many experts.
"I don't think it's a good idea," said Dr. Robert Knopp, veteran director of the UW's Northwest Lipid Research Clinic about OTC sales. "They need to be managed by prescriptions.
Knopp said a statin can interact with other drugs and cause major problems. Baycol, or cerivastatin, was recalled after reports of 52 patients dying, many of whom were taking another anti-cholesterol drug along with it.
And many patients, Knopp said, could gain a false sense of security from taking statins. The drugs lower but don't eliminate risk of heart attacks.
Brown said a 35 percent reduction in heart-attack risk is about the maximum that can be achieved by lowering LDL. More efforts, he said, are needed to increase HDL (high density lipoprotein), the so-called "good" cholesterol that helps clear cholesterol from the body.
Niacin, a B vitamin, and fibrates, compounds which also lower triglycerides, have both been shown to raise HDL and sometimes are taken in combination with statins, Brown said. A new drug called a CETP inhibitor, which also may raise HDL as much as 50 percent, is being studied but has not been approved by the FDA.
"Statins have revolutionized the treatment of cardiovascular disease,
but they're not a cure," said Brown. "A combination of drugs are more the
Copyright © 2004, Seattle Times