Should statin drugs be put in the water, or what?
More than 13 million Americans are taking these medications to lower their cholesterol and hopefully stave off heart disease -- a job the drugs appear to excel at. Statins can lower "bad" LDL cholesterol by 20% to 60%. Over time, this can lower the risk of having a heart attack by about the same amount.
For many years, it was believed that statins worked solely by reducing blood cholesterol, which can build up in sticky plaques in the arteries that supply blood to the heart, potentially blocking blood flow and causing heart attacks. But evidence is mounting that the drugs reduce heart disease risk through more than just their cholesterol-lowering effects. New research suggests they may be beneficial even for people with cholesterol in the normal range.
This has doctors and medical researchers debating whether many more people should be on statins than currently fall under treatment guidelines. Some drug companies and doctors have even argued that low doses of the drugs should be available over the counter, as they are in the United Kingdom.
At the same time, other studies are reporting that statins might help prevent or treat a number of noncardiovascular conditions -- including multiple sclerosis, cancer and Alzheimer's disease. With all this news, many may be wondering, "Should I take a statin, just in case?"
Experts, for the most part, will say only, "Maybe."
Most of the people at high risk of cardiovascular disease "are going to be safer and live longer if they're on a statin than if they're not," says Nathan Wong, director of the UC Irvine Heart Disease Prevention Program. But that doesn't hold for people whose risk for heart attacks is very low to begin with, he adds. "I'm not saying that everyone is going to be better on a statin. They need to be used with discretion."
All six statins available today -- atorvastatin (Lipitor), rosuvastatin ( Crestor), simvastatin (Zocor), lovastatin (Mevacor), pravastatin (Pravachol) and fluvastatin (Lescol) -- work by blocking an enzyme called HMG-CoA reductase.
In the liver, blocking this enzyme shuts down cholesterol production and increases the amount of cholesterol the liver takes out of the bloodstream.
But statins also block HMG-CoA reductase in the cells lining blood vessels, where, among other things, they can reduce inflammation.
The anti-inflammatory effect of statins has been on many heart experts' minds since the Nov. 9 announcement of the results of a clinical trial called JUPITER. The trial showed that statin treatment can reduce the risk of heart disease in people with normal cholesterol levels but high levels of inflammation as measured by blood levels of a marker called C-reactive protein (CRP).
A team led by Dr. Paul Ridker of Brigham and Women's Hospital in Boston and Harvard Medical School found that in 8,901 people with high blood CRP levels, rosuvastatin (Crestor) reduced the risk of a heart attack by 54% and the need for bypass surgery or angioplasty by 46% compared with an equal number of people taking a placebo.
There were 68 heart attacks and 131 bypass surgeries/angioplasties in the placebo group, but only 31 and 71, respectively, in the group taking the statin. There were 48% fewer strokes -- 64 versus 33. These effects were so dramatic that regulators stopped the trial, slated to go for four years, after less than two. AstraZeneca, the company that makes Crestor, funded the JUPITER trial.
The results raise an obvious question: Are the cholesterol-lowering effects or the inflammation-reducing effects of statins more important?
Dr. Christopher Cannon, a cardiologist at Brigham and Women's, says they both play a part: "You have to have some cholesterol get into the arteries [and cause damage]. And if you have inflammation that damages the lining of the arteries, the cholesterol gets in more easily."
Inflammation can also encourage plaques to rupture, causing clots that block blood flow. "Both [cholesterol buildup and inflammation] are happening simultaneously, and both are inhibited simultaneously with statins," Cannon says.
Currently, more than 13 million people take statin drugs for elevated LDL cholesterol, and at least 47 million more have cholesterol levels high enough to make them eligible by current National Heart, Lung, and Blood Institute cholesterol guidelines.
Ridker estimates an additional 4 million to 6 million people would be added to the mix if everyone who would have qualified for the JUPITER trial (men over 50, women over 60, LDL cholesterol below 130 mg/dL and CRP above 2 mg/L) started taking a statin.
Statins may be good for more than just fighting heart disease.
Very preliminary studies suggest that the anti-inflammatory effects of statins could help treat autoimmune diseases. A small, nine-month study of 36 patients with multiple sclerosis published in April in the journal PLoS One showed that statin treatment, either alone or combined with standard MS treatment, reduced the number of brain lesions characteristic of the disease by 24% and reduced their size by about 12%.
Another pilot study of just seven people, published in September 2007 in the Journal of the American Academy of Dermatology, showed that a statin reduced the severity of the skin disease psoriasis.
A combined analysis of 19 studies, published in August in the International Journal of Cancer, found that statin use reduced the risk of advanced prostate cancer by 23%.
And a study published in November in the Journal of the National Cancer Institute showed that men prescribed statins had a 4.1% decline in their blood levels of prostate-specific antigen (PSA), a marker of prostate cancer.
There is some evidence that statins can lower the risk of developing Alzheimer's disease. An October study of almost 7,000 people in Rotterdam, Netherlands, found that people taking a statin had about a 50% lower risk of Alzheimer's compared with those who had never used cholesterol-lowering medication. Other studies, however, have failed to find an effect of statins on the risk for dementia or Alzheimer's disease.
As the benefits of these drugs are experienced by more people, the risks will be too. Though statins are generally considered safe, they do have side effects.
Drugs' side effects
The most commonly reported adverse event associated with statins is muscle pain. A 2006 analysis of seven clinical trials published in Medscape General Medicine found that 2.5% to 6% of patients taking statins reported aches and pains related to their drugs.
Rhabdomyolysis, a breakdown of skeletal muscle that can lead to kidney failure and sometimes death, has also been linked to statins. According to the 2006 Medscape report, less than 0.1% of patients taking statins reported rhabdomyolysis. There was only 0.15 death from rhabdomyolysis per 1 million prescriptions.
Liver effects are also seen in some patients taking statins. In less than 1% of patients taking moderate doses of statins, and in about 2% to 3% of those taking high doses, liver enzyme levels are abnormally high. But the enzyme changes usually subside after discontinuing statin use or switching to a different statin, says Dr. Antonio Gotto, dean of Weill Cornell Medical College in New York.
In 2007, the Food and Drug Administration conducted an investigation into whether statins increase the risk of the fatal neurodegenerative disease amyotrophic lateral sclerosis, also known as Lou Gehrig's disease, when the agency received a higher than expected number of reports of the disease in people taking statins. Although an analysis of 41 long-term controlled clinical trials reported in September detected no such link, the FDA has said it plans to continue studying the issue.
Dr. Scott Grundy, a professor of internal medicine and director of the Center for Human Nutrition at the University of Texas Southwestern Medical Center at Dallas, says he thinks the drugs, on balance, are safe. But he adds that caution is still warranted, especially when it comes to considering a broad expansion of their use or prescribing them earlier in people's lives.
Statins have been in use only since the late 1980s, he notes, and so there hasn't been enough time yet to learn what might happen if someone were to be on the drugs for 30 or 40 years. "It is possible that some of these rare side effects might turn out to be quite important if [statins are] started early in life and continued for years and years," he says.
Whether statin use is substantially expanded may depend on how the results of the JUPITER trial and other recent research are incorporated into new cholesterol guidelines slated to be released next year by the National Heart, Lung and Blood Institute.
If CRP testing becomes part of the standard battery of tests that guide risk assessment and statin treatment decisions, millions more Americans could find themselves filling a prescription.
Currently, most doctors use CRP testing as a sort of tie-breaker when they are on the fence as to whether a patient is at high enough risk of heart disease to warrant statin therapy. Patients might, for example, have intermediate cholesterol levels but a family history of heart attacks or some other risk factor.
Dr. Mary Malloy, co-director of the adult lipid clinic and director of the pediatric lipid clinic at the UCSF Medical Center, does not think this should change, even though she characterizes the JUPITER results as "very impressive."
"I am personally not ready to corral everyone over 35 and do CRP testing," she says.
Wong says it's important that people take into account a person's absolute risk when judging whether or not a patient needs a statin.
Of the JUPITER trial, he says, "There was a 44% reduction in cardiovascular events. This sounds very dramatic, and it is." But the risk of heart attack in those patients was pretty tiny to begin with -- 2.8%. The 44% drop took it down to 1.6%.
The bottom line is that monetary cost as well as potential side effects of statins must be weighed against the potential benefits.
Wong's biggest concern is that people will get the idea that statins are a cure-all -- and they'll stop bothering about habits that could affect their heart health just as much.
"People think statins are magic pills," he says. "You can't forget about other risk factors like smoking, diabetes and blood pressure. . . . you have to make sure all these things are adequately controlled."
--Copyright © 2014, Los Angeles Times