WEDNESDAY, July 23, 2008 — Cholesterol-lowering drugs like simvastatin (Zocor) and atorvastatin (Lipitor) are one of the great health breakthroughs of the 20th century—they’re safe and can dramatically lower LDL, the bad cholesterol. But they’re not risk-free: Some people experience muscle pains, known as myopathy, which can make taking the drugs unpleasant and, in rare cases, lead to a life-threatening condition.
Now a new study suggests that 15% of the population may have a specific genetic variant that increases their risk of experiencing statin-related muscle aches.
In the new research, a University of Oxford team sequenced the genes of 85 people who developed myopathy after taking high-dose simvastatin (80 mg) in a larger trial of 12,000 people. They compared the DNA of those subjects with 90 people in the same study who did not develop myopathy.
What they discovered was that one small change in a gene that is responsible for transporting drugs in the liver was associated with myopathy.
People who inherit a single copy of the genetic variant from a parent were 4.5 times as likely to develop myopathy, and those with two copies (one from each parent) were almost 17 times as likely to develop the condition when taking a high-dose statin compared with those without a copy, according to the study in The New England Journal of Medicine.
It’s a common problem
About 1 in 10,000 people per year who take regular doses of statin drugsdevelop myopathy, according to the study, though the risk goes up with higher doses. According to Merck spokesperson Ronald Rogers, the incidence can be as high as half of 1% (roughly 1 in 200) for those taking large, 80 mg doses of Zocor for at least four years.
However, Leslie Cho, MD, director of the Women’s Cardiovascular Center at the Cleveland Clinic in Ohio, says a higher percentage of patients in the real world may complain of muscle aches.
“Muscle aches on statins is rarely reported in [clinical] trials because drug companies don’t want to look for that, but it’s a very common thing that clinicians hear every day,” she says. “It’s especially common in the elderly and we are always trying to look for ways to make that better. If there is a predisposing genetic thing for it, that would be a good thing.”
Gene test could be used in the clinic, but not likely
If further research confirms the findings, and a cheap enough gene test is developed, doctors could one day use it to help determine if a patient who is a candidate for a statin might be at risk for developing myopathy.
However, those are some big “ifs,” and such a test may not be cost-effective for every patient, according to experts.
“Now would I use this on every patient before I started statins? I don’t think I would,” says Dr. Cho, who was not involved in the new research. “To get this test on every single patient before they start statins would not be cost-effective unless it is incredibly cheap.”
Donna Arnett, PhD, a spokesperson for the American Heart Association, confirmed that the findings are important, but a long way from being used routinely in doctors’ offices.
“There are a lot of steps until we get to that clinical testing in your doctor’s office,” says Arnett, a chair and professor of epidemiology at the University of Alabama at Birmingham who does research in genetic epidemiology. The new findings need to be replicated in other patients and with other statins, but if it holds true, it could result in a useful test, according to Arnett.
How serious is myopathy?
Dr. Cho says that many statin-taking patients who experience some pain think they have myopathy, but the condition is more than minor aches and pains. Doctors look for pain and weakness in large muscle groups on both sides of the body, such as the buttocks, upper arms, and upper legs.
And many people don’t know that a host of other things can increase their chances of myopathy in combination with statins—including excessive alcohol intake and drugs such as cyclosporine (an anti-rejection drug), fibrates (a cholesterol-lowering drug), macrolide antibiotics (such as erythromycin), antifungals (like fluconazole), protease inhibitors (used to treat HIV), and colchicine (used to treat gout).
Patients can often reduce their risk by talking with their doctor about possible drug interactions.
Gene’s link to more serious side effect is unknown
While myopathy is a relatively common side effect, it can progress to a rare and potentially life-threatening side effect called rhabdomyolysis, which occurs when muscle actually breaks down and leads to kidney failure.
“The thing we worry about the absolute most is rhabdomyolysis, which is life-threatening,” says Dr. Cho. In contrast, myopathy is “very benign but it’s obviously lifestyle-limiting for patients.”
The incidence of rhabdomyolysis is estimated to be 44 events per 1 million statin users per year, according to an editorial accompanying the study. It’s not clear if the gene variant is linked to rhabdomyolysis, but testing for a link should begin “as soon as possible,” writes Yasuke Nakamura, MD, of the University of Tokyo.
While more research is needed, Dr. Cho says she could see a gene test being useful in patients who develop myopathy after taking the drugs.
“But I think that to have a carte-blanche statement that every patient that gets started on statins should have this test is kind of overkill.”
The study was funded by a research grant from Merck to the University of Oxford.
(PHOTO: GETTY IMAGES/DRUG3K.COM/HEALTH)
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Comments (14)
I’ve been on Simviat(Zocar) for three years. I have been having muscle spasms in my back, rib cage and
legs for years. My doctor tells me to stretch. I do. Recently I have been having spasms in my legs, feet and the rest of my body. a spasm was so bad in my leg one night it took 20 minutes to relax. I no longer kneel on the floor at chapel because that’s whe it occured and I am afraid Ii won’t be able to get up next time.
I took Statins (Lipitor) for some months several years ago & got muscle problems (upper arm muscles feel as though weak, but not actually weak, & often with fatigue). Symptoms stop but then start again if I carry even slightly heavy things & last for 3 days; I paddled very lightly in a pool recently & had this 3 more days. Lipitor started it, but it comes on with no muscle straining if I start Zetia or Vytorin or Pravachol. Since my doctor tested & found CPK Levels normal, he said it wasn’t the Pravachol (recently), but doesn’t yet realize I stopped the Pravachol 9 days before lab test. For a long time it was only that miserable tender upper-arm (both sides) feeling, & feeling as though muscles are weak, but hardly any actual pain. Lately, there’s some pain with it, too. I also have (unrelated maybe) a right elbow that “goes up & out” automatically when I type or write, causing type errors since then my hand twists – seems to come from a shoulder problem. Any idea if it is statins, or could it be something else? [Of 6 people I met one year who took statins, 5 had muscle problems – it’s underreported, and I don’t believe makers of Lipitor are telling everything. It goes away, as they say, but keeps coming back! Or do I have some other disorder that only coincided with statin use?
Vytorin was responsible for the most agonizing muscle pain. I felt I was having s seizure it affected both legs & I was screaming with pain that nothing could relieve. It lasted for a half hour & then an hour later came back as bad as before but of less duration. I am now on Crestor but nervous that sooner or later the same thing will happen again. I wish someone could recommend a natural non-prescription product that would lower my elevated cholesterol. High Fiber products like Metamucil & Fiber One tablets tend to produce a chocking sensation & as I have an erosive gastroesophageal condition & occasinal GERD – I cannot take such products. Any help out there? Thank you.
C. E. Preston
I was on Crestor for 1.5 yrs, then started getting muscle cramps and leg pain. CPK was elevated too. Stopped the statin and cramps went away, CPK returned to normal. Tried lipitor with same results only more severe. It’s taken about 3 months for the cramps and leg pain to finally subside since stopping the lipitor. My Dr. says he sees this more frequently than the public is led to believe. I too believe problems with statins are underreported.
I have been on Simvastatin(Zycor) for 3 years. The past few months I have had muscle spasms in my rib cage, as well as. feet and lower calves.
I was put on Zocor in early May. I started having severe muscle pain in my legs by early June. Having injured my knee during the winter, at first I thought that was why I was hurting. Finally, a nurse-colleague asked me about the pain I was having, since I could barely walk. She suggested it might be the Zocor. I called my doctor immediately. He was out of town. His partner simply told me to stop taking the medicine. In a few days the pain subsided.
Now, it is back. I could barely walk this weekend. I am calling my doctor as soon as I can.
I posted a few months back about my leg pain subsiding, but it seems to have gotten a bit worse again. Stephanie Walker, I’ll be interested to see what your doc tells you about other causes of leg pain, because I’ve been off the statins for over 6 months now. Am trying the time release niacin and very little dietary cholesterol plus fish oils. Will recheck the lipid profile in 6 weeks…
I tried Zocor, Lipitor & finally Crestor. As soon as I was put on my first one I began having attacks of acute joint &/or muscle pain. It began in my hips and then migrated into other places, like my hips, knees, hands and shoulders. I stopped taking the Crestor 4 months ago and the effects seemed to stop almost at once, however they have through the time off the drug and just a couple weeks ago seemed to pop up intermittently and migrate to arms, hands, hips knees and shoulders. It doesn’t happen as often now, but the acute pain can match the pain I originally.
I have been on statins for about 5 years now and have had constant pain in both legs and upper arms. Also I have sudden spasms in my rib cage and in my back so bad that it takes me to the floor. My doctor told me to take 100 mg of CoQ10 twice a day but it doesn’t stop the pain.
I didn’t take my statin yesterday and I already feel a difference in my legs. The pain is not completely gone but it is at least 80% better. I stopped taking them once before and my doctor told me not to stop taking them because my LDL and triglycerides were elevated. I might just take them a couple of times a week instead of daily and see if it causes problems.
Iam taking Micronized Colestiol HCL 1GM Its not suppose to give you muscle spasm, but I get them below my kness to my feet and also my rib cage.Why doesnt the doctor recommend sonething natural if this happens to so many people. e.g. Red Yeast Rice is a natural supplement. Go to your nearest Health Food Store they can recommend something like Red Yeast Rice.
i took LIPITOR for ?years. First my shoulders ached (i blamed my job of sitting at a computer for 10 hrs a day) then my left elbow ached,next my upper left arm muscle ached and then my upper right muscle ached. It hurt so bad at night my muscle in left arm actually throbbed. I finally mentioned it to my Dr. and he said STOP THE LIPITOR. As someone said above I felt immediate releif but then it was not long and the aching arm muscles were back. Dr. tried me on 2 other cholestrol meds but immediately I knew I could not take them. Now my chlosteral is 250, my Dr. has me on 1 Crestor a week & am to go for blood work in 6 weeks. I had not heard of “STATINS” until my Dr. told me to stop taking LIPITOR. The aches come & go, I take at least 2-4 Alieve a day trying to get relief when arms ache and throb. I believe the person who said THE PROBLEMS WITH STATINS ARE UNDER-REPORTED hit the nail right on the head. Heaven forbid the pharmacutcal(spelling not correct) companies lose some of the multi billion of DOLLARS they are raking in.
I have been on Zocor for about 3 years. I have recently experienced more and more severe muscle spasms in my rib cage, legs and triceps. The spasms have also effected my sleep. At nights I wake up thinking someone is poking at me but it turns out to be the spasms. I was starting to get concerned and then saw that I’m not alone. Going to talk with my Dr. to see if I can control chol on something different.
Thank God, I am not alone. I have been on Lipitor for over 5 yrs (7?) Started to experience muscle weakness and periodic spasms, over a year ago. Now I have intermittent pain in the lower legs. Have had all tests on circulation, bone density, eccho/carotid sonograms and extensive blood work..all showed normal with just a slight degree of inflammation. No arthritis/RA. I took myself off the statin almost 3 weeks ago. Pain is a bit better, but my extensive research says it could take many months to subside. I will not go on a statin again, and certainly not until these aches subside. I can’t sleep and am on pain killers and sleeping pills. I think it is statin induced myopathy, and is definitely under reported by doctors and the pharmaceutical industry! I go for blood tests every three months and most of the time nothing is elevated and my cholesterol is controlled, but at what price? I hope my muscles/nerves aren’t permanently damaged..
It took me several months to get over the leg pains and spasms. Am now on 1000mg Niaspan for over a year and my cholesterol is right at 200 (down from 265 without meds). No leg pain, just occasional flushing from the niaspan. Don’t know why this isn’t prescribed more often?