Dr. Paul D. Thompson, MD, describes a six-month placebo-controlled study of high-dose atorvastatin and skeletal muscle. He explains what share of muscle pain he attributes to the statin, what happened to exercise capacity and strength, and which rare symptom calls for prompt medical attention.
Statin Muscle Symptoms: Clinical Trial Findings, Exercise Capacity, and Rare Weakness
Jump To Section
- Research on statins and skeletal muscle
- How muscle pain was defined and tracked
- How often the statin caused the pain
- Exercise capacity and muscle strength
- Cramping and staying on a statin
- Rare muscle weakness on a statin
- Full Transcript
Research on statins and skeletal muscle
Statin muscle symptoms have been a long-standing research interest for cardiologist Dr. Paul D. Thompson, MD. Dr. Anton Titov, MD, asks him how common these symptoms are and whether statins lower athletic performance. Dr. Thompson traces his interest in skeletal muscle back to the 1970s, when he was a distance runner. He says his group published one of the first research articles, in 1990, showing that exercising on a statin raises evidence of skeletal muscle injury.
He then describes a study that he thinks is the only one designed solely to look at the effect of statins on skeletal muscle. It enrolled 420 people who had never taken a statin. Half received 80 milligrams of atorvastatin, which he notes is the highest dose, and half received a placebo that looked just like it. Neither the participants nor the investigators knew who was taking which pill, and treatment lasted six months.
How muscle pain was defined and tracked
Muscle pain in the study was tracked closely. Dr. Thompson says the team measured exercise performance, lipid levels, and several types of muscle strength at the start and again at six months. Participants were also called every two weeks and asked about symptoms.
To count, the pain had to come on and bother the person, go away within two weeks of stopping the pill, and come back when the pill was restarted. He notes that most muscle discomfort due to a statin goes away shortly after the statin is stopped.
How often the statin caused the pain
Statin-related muscle pain, by this definition, occurred in 10% of people taking high-dose atorvastatin and in 5% of people taking placebo. Dr. Thompson therefore puts the true incidence of statin muscle complaints over the six months of the study at 5%. He adds that for most people the discomfort was not enough to stop the statin, and that he does not think anyone else has done such a carefully designed study.
Exercise capacity and muscle strength
Exercise performance did not decline in the study. Dr. Thompson reports no decrease in aerobic capacity, measured by gas exchange on a treadmill, and no consistent changes in muscle strength. His conclusion is that statins can cause muscle symptoms, that these are usually mild, and that he does not think they interfere with exercise performance or muscle strength. He cautions that the study lasted only six months.
Cramping and staying on a statin
Personal experience shapes his view as well. Dr. Thompson thinks statins affect skeletal muscle and can cause cramping in some people, including himself: he has to take a statin and gets fairly severe cramping every once in a while. He thinks statins can cause mild muscle pain (myalgia) in some people, yet he calls them generally extremely well tolerated.
His view is that a person who needs a statin should be on it. He often uses the phrase "one heart attack cures statin myopathy." He describes many patients who could not take a statin because their muscles hurt so much, until a heart attack nearly cost them their life; after that, the statin did not seem so bad.
Rare muscle weakness on a statin
Muscle weakness is what Dr. Thompson says separates the rare reaction from ordinary statin complaints. Very rarely, in about 1 in 5,000 to 1 in 10,000 people, he says, a statin triggers what he describes as an allergy to their own muscle, directed at HMG-CoA reductase, the enzyme in muscle that statins affect. Unlike people with mild statin complaints, these patients develop weakness.
He advises anyone who develops muscle weakness on a statin to talk to their doctor fairly promptly. The statin has to be stopped, and many times treatment to suppress the immune system is also needed. He stresses that this is very rare.
Dr. Thompson calls the topic of statin muscle complaints, in his view, totally overblown, while saying he has no doubt that statins can cause muscle symptoms that are most times totally tolerable. For people who are concerned, he points to a long series of short posts on statin muscle symptoms on his blog.
Full Transcript
Dr. Anton Titov, MD: Statin muscle symptoms, muscle pain on a statin. You were principal investigator of a randomized clinical trial of a statin and skeletal muscle function. In healthy volunteers, muscle complaints were more frequent with the statin than with placebo. Average muscle strength and exercise capacity did not differ from placebo. Professor Thompson, how common are muscle symptoms in people taking statins? Do statins lower athletic performance?
Dr. Paul D. Thompson, MD: Those are a great series of questions. I was always interested in skeletal muscles since the 1970s because I was a distance runner. So I was very interested in skeletal muscle injury and skeletal muscle breakdown, things like that.
Dr. Paul D. Thompson, MD: In 1990 we published one of the first papers showing that if you exercise on a statin, your evidence of skeletal muscle injury goes up. So we have always been interested in it. So we did what I think is the only study designed solely to look at the effect of statins on skeletal muscle.
Dr. Paul D. Thompson, MD: We took 420 people who had never been on a statin before, so they were not selected in any way. We gave half of them 80 milligrams of atorvastatin, the highest dose of atorvastatin. We gave the other half of them a placebo that looked just like the atorvastatin pill.
Dr. Paul D. Thompson, MD: They did not know what they were on, we did not know what they were on, and we treated them for six months. We measured their exercise performance, their lipid levels, and all sorts of types of muscle strength at the start. We repeated those muscle strength and exercise performance measurements.
Dr. Paul D. Thompson, MD: We repeated them at six months, and what did we find? Oh, and the other thing we did is we called them every two weeks. We called people every two weeks to ask if they had any symptoms.
Dr. Paul D. Thompson, MD: So what did we find? We found that 10% of the people on the statin got muscle pain, and the muscle pain had to be the following. It had to come on and bother them.
Dr. Paul D. Thompson, MD: It had to go away within two weeks of stopping the medications. Most muscle discomfort due to the statin will go away shortly after stopping the statin. It had to come back when we put them on the statin.
Dr. Paul D. Thompson, MD: So 10% of patients on the high dose of atorvastatin, the highest dose, got muscle symptoms. In the placebo group, 5% of the patients had pain that came on with the medication. It went away within 2 weeks of stopping the medication.
Dr. Paul D. Thompson, MD: And it came back when we restarted the medication. So we think that about 5% of people on placebo have symptoms. 10% of people on the statin have symptoms. So the true incidence of statin muscle complaints over the six months of our study was 5%.
Dr. Paul D. Thompson, MD: Now, the discomfort was not enough for most people to stop the statins, but it occurred. We do not think anybody else has done such a carefully designed study. We found no decrease in their aerobic capacity measured by gas exchange on a treadmill.
Dr. Paul D. Thompson, MD: We found no consistent changes in muscle strength. So our conclusion is yes, statins can cause muscle symptoms. They are usually mild.
Dr. Paul D. Thompson, MD: We do not think they interfere with exercise performance or muscle strength. But remember, our study was only six months. Do I think statins affect skeletal muscle?
Dr. Paul D. Thompson, MD: Yes, I think they affect skeletal muscle. I think they can cause cramping in some people. They do in me.
Dr. Paul D. Thompson, MD: I have to take a statin. I get fairly severe muscle cramping every once in a while. I think they can cause some people to get mild, mild muscle myalgia, but generally statins are extremely well tolerated.
Dr. Paul D. Thompson, MD: If you need the statin, I think you should be on it. I have a phrase that I often say, and that is that one heart attack cures statin myopathy. I have so many people who cannot take a statin because their muscle hurts so much, and then they get a heart attack and nearly lose their life.
Dr. Paul D. Thompson, MD: And you know what? The statin is not so bad. Now, there is one other thing we need to talk about.
Dr. Paul D. Thompson, MD: Very, very rarely, about 1 in 5,000 to 1 in 10,000 people actually get an allergy to their own muscle from the statin. Statins affect something called HMG-CoA reductase in the muscle. And what these people do is they actually develop an allergy to HMG-CoA reductase.
Dr. Paul D. Thompson, MD: They develop an allergy to their own muscle. Now, what is different between them and the usual person with mild statin complaints? These people develop weakness.
Dr. Paul D. Thompson, MD: We rarely see weakness with statins, but these people with this myopathic allergy actually develop muscle weakness. So if you actually get muscle weakness on a statin, you should talk to your doctor fairly promptly, because you need to get off the statin, of course, but also, many times, we have to put you on drugs to suppress your immune system because you are reacting to the statin so vigorously. Now, remember, that is a very rare occasion.
Dr. Paul D. Thompson, MD: And if you want to know more about this stuff with statin muscle things, because I think it is totally overblown: there is no doubt in my mind, as a practicing clinician cardiologist who sees a lot of patients, that statins can cause muscle symptoms, most times totally, totally tolerable. But I did a long series of posts. All the posts on my blog are two- to three-minute reads, but I did a long series of posts on my blog about statin muscle symptoms.
Dr. Paul D. Thompson, MD: It is probably worth you taking a look at if you are concerned about that.