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Drugs that target high cholesterol come with new cautions

New FDA warnings about the side effects of cholesterol-lowering statins have physicians and patients weighing the risks and benefits of taking these drugs

Cholesterol-lowering statins, prescribed to some 30 million Americans, have begun to lose a bit of their luster. Signs are starting to appear that the risks of taking statins may outweigh the benefits for people at low risk of having a heart attack. Some doctors have begun to question the wisdom of putting young adults with high cholesterol on statins for decades, and many expressed outrage at national guidelines issued last year to test cholesterol levels in 9-to-11-year-olds, which could result in a surge of children being placed on statins.

A set of warnings and safety recommendations issued in February by the US Food and Drug Administration require that statin labels include information about the possibility of cognitive side effects such as memory loss and confusion, and an increase in blood sugar levels that could trigger type 2 diabetes. Already on manufacturer websites, the warnings will soon be appearing on the package inserts that accompany prescriptions.


To be certain, statins ­— which include Lipitor (atorvastatin), Crestor (rosuvastatin), and Zocor (simvastatin) ­— remain a vital part of the arsenal of heart disease drugs. For people with established heart disease, taking a statin can reduce the risk of a having a heart attack or dying of heart disease over the next decade by about 30 to 40 percent. They work by blocking the production of “bad” LDL cholesterol in the liver while at the same time moderately raising “good” HDL cholesterol and reducing hazardous inflammation throughout the body — all of which can help prevent dangerous plaque from forming in arteries.

About 10 percent of statin users, however, develop muscle aches that make it tough to stay on the drugs. The negative cognitive effects can range from temporary memory loss or confusion to full-blown Alzheimer’s-like dementia. Potentially life-threatening side effects such as muscle-tissue death or kidney or liver damage occur in fewer than 1 in 10,000 statin takers.


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“The vast majority of people on statins get more benefits than risks from the drugs,” said Dr. JoAnn Manson, chief of preventive medicine at Brigham and Women’s Hospital, whose recent research found a link between women’s use of statins and their diabetes risk “The concern is that an increasingly large number of people at relatively low risk of heart disease are being started on statins at a young age and kept on them for long durations, and it isn’t entirely clear that the net benefits they’re getting are outweighed by the risks.”

Decade-old guidelines for using statins and other drugs to lower cholesterol levels are set to be updated by a panel convened by the National Heart, Lung, and Blood Institute this year, and some experts wonder whether they should be tightened to exclude those who aren’t at high risk of having a heart attack. The current guidelines recommend treatment with cholesterol-lowering drugs to prevent heart disease in those who have elevated LDL cholesterol levels of 160 mg/dL or higher if they also have two other heart disease risk factors such as a low HDL level of below 40 mg/dL, and increased age, defined as 45 or over for a man and 55 and over for a woman.

Most people on statins take them to prevent heart disease either because they have diabetes, which increases heart disease risk, or bad cholesterol numbers. Yet a 2011 study from the Cochrane Collaboration, a nonprofit international research organization, which reviewed data from 14 trials involving more than 34,000 patients without heart disease, found that treating about 1,000 people with statins for one year prevented just one death. Since most patients in the studies were men, it’s still unknown whether women gain even this tiny mortality benefit.


“There isn’t a sea change yet, but there needs to be some serious questions asked about whether we’re overprescribing statins,” said Dr. Eric Topol, a cardiologist at the Scripps Clinic in La Jolla, Calif., and author of “The Creative Destruction of Medicine.” “I see so many patients where the only thing wrong with them is their LDL cholesterol level and taking a statin makes their lab tests look pretty, but is that worth the risk of diabetes?”

According to drug manufacturer-sponsored clinical trials reviewed by Cochrane and others, about 2 per 100 patients taking statins to prevent heart disease will be spared from a heart attack or other cardiovascular event for every five years of treatment; that compares to an extra case of diabetes for every 200 patients treated for five years. Those on higher doses of more potent statins like Crestor have higher rates of diabetes — one extra case for every 125 patients treated, Topol said. Treating with statins for a decade or more could mean even more cases of diabetes, to the point that the risks exceed the benefits, he said.

“I think you need to explain this to the individual patient,” said Dr. Richard Karas, director of the preventive cardiology center at Tufts Medical Center. “One patient may say her mother died of diabetes, and she doesn’t want to take a drug that will increase her risk, while another may say her mother died of a heart attack so she wants to take a statin.”


A recent informal survey of 30 primary care physicians at Brigham and Women’s Hospital found that 24 out of 30 physicians said they were “somewhat concerned” about the side effects of statins when prescribing them to prevent heart disease and that one-third of the survey respondents said their level of concern had increased in the past year. Only two doctors, though, reported curtailing their prescribing habits.

Increased concerns about side effects were also evident in a March survey of nearly 800 cardiologists conducted by a physician-run website called theheart.org. About 13 percent of these respondents said they often observe blood sugar levels increases in patients who begin taking statins and nearly a third said they’ve seen cognitive side effects from statins.

Treated with Zocor seven years ago, in his early 50s, Robert Grindell found his short-term memory began to deteriorate. “My co-workers told me I was coming in to ask them the same question three times in one day,” said the Makinen, Minn, resident. After learning that Zocor can cause memory problems, Grindell decided to go off it and said his memory problems vanished. He now wonders whether the type 2 diabetes he developed while on the drug was due to the usage.


Con Squires, on the other hand, said he’s a “total fan of statins” and has never experienced any side effects after taking them for more than a decade. The 75-year-old from Nahant takes 80 milligrams of Lipitor daily to lower his LDL and said he doesn’t have any signs of diabetes.

Some groups of people are more likely to develop problems from statins, such as those who are elderly, people who are short and small-boned, and those taking certain medications that render statins more potent (including certain anti-fungal medications and antibiotics; also, grapefruit juice). In general, women develop more problems than men.

“I always consider the possibility of statin-associated side effects if patients develop symptoms after a statin is started,” said Dr. Valentin Fuster, director of the heart program at Mount Sinai Medical Center in New York City. In such cases, patients may be taken off the drugs for a month to see whether symptoms resolve. “But I also want to emphasize that statins shouldn’t be stopped because of fears about the new FDA warnings; we’ve received calls from patients concerning this, and I told them stopping their statins could be dangerous” in terms of raising their risk of heart problems.

Deborah Kotz can be reached at dkotz@globe.com. Follow her on Twitter @debkotz2.