Statins — among the most successful drugs ever developed — prevent deaths from heart attacks and strokes but have long been dogged by the notion that they also cause muscle pain in some people. Now that belief has been called into question by a new study.
The trial asked older patients who stopped taking statins (or were considering doing so) because of pain to go back on the drug or take a placebo. Crucially, they didn’t know which they were getting, and there was no difference in the aches and pains people reported.
“While in these older age groups, aches and pains are indeed common, we convincingly show they are not made worse by statins and their pain is not caused by statins,” Liam Smeeth, an author of the study published Wednesday in the BMJ, told STAT.
Statins won regulatory approval in the late 1980s based on how well they lowered cholesterol and triglyceride levels, which are tightly linked to damaging hearts and blood vessels. Credited with cutting cardiovascular deaths by one-third, the drugs have also been connected to rare problems such as rhabdomyolysis, in which the breakdown of muscle tissue releases a damaging protein into the blood, in 1 out of 10,000 people who take them.
Less serious but more common muscle pain — experienced by up to 5% of patients — and joint aches can cause people to stop taking the drugs or never start, especially following media reports tying statins to diminished quality of life, Smeeth said. A flurry of news stories and declines in statin use spurred the general practitioner who’s also an epidemiologist at the London School of Hygiene and Tropical Medicine to devise a trial using a design that allows a person to be in both the treatment and the placebo arm — and compare their own experience in each.
The study enrolled 200 participants from 50 general practices in England and Wales who chose to stop taking statins and asked them to take either 20 milligrams of the statin atorvastatin (the generic version of Lipitor) daily for two months, or a dummy pill for two months, and then switch back and forth over six two-month periods. All along, they ranked their pain every day on a scale of 1 to 10, without knowing if they were taking the real drug or the dummy pill.
After the trial ended, there was no difference in the frequency or severity of muscle symptoms scored by participants, even though they had previously said they had severe muscle symptoms when taking statins. When the researchers explained to participants that the statin made no difference in the pain they felt, two-thirds of the people decided to go back on the drug.
“People can take statins in full knowledge that their pain is not being made worse by statins,” Smeeth said. “That means they can get all the benefits of reducing heart attacks and strokes without worrying about the pain.”
There could be many other causes for pain. The average age of the participants was 69, when aches and pain are common. There’s also the “nocebo effect,” in which expecting a side effect from a drug leads people to attribute what they are feeling to the drug. A smaller trial using this approach, published in November, had similar results among its 60 participants.
“Both [trials] strengthen the case that genuine side effects from the statin molecule (rather than the nocebo effect) are much rarer than most people think,” James Howard of Imperial College London and an author of the earlier study, in the New England Journal of Medicine, told STAT. He was not involved in the BMJ study. “We found 50% of our patients … had successfully restarted statins six months after they finished the trial,” he added.
These trials offer more validation for the idea that statins are safe, Harlan Krumholz, a Yale cardiologist who was not involved in either trial, told STAT. He led a 2006 systematic review of randomized statin trials that failed to find evidence of increased muscle pain.
The story doesn’t end with these study results, Krumholz said.
“You never want to dismiss out of hand something that’s being experienced by the patient. Telling a patient that it’s all in their head isn’t a very successful strategy for helping to navigate problems that people are experiencing,” he said. “Just letting people know about studies like this could be helpful in practice.”
Large clinical trials tend to focus on life-threatening side effects and not on less serious ones like muscle pain, but Krumholz pointed out that if people quit their statins, they may put themselves at higher risk of death from the heart attacks and strokes statins are prescribed to prevent.
“We need to pay a lot of attention to these kinds of complications. They tend to be put off because they in themselves do not threaten people’s lives, but they move people away from strategies that can save people’s lives,” Krumholz said. “We need to find ways to determine when the medication is causing problems and what might be just concerns, anxiety, and expectations that are leading people to experience things.”
The recent trials are called “n-of-1” studies because the participants are their own comparison group. Smeeth has been thinking about adapting the spirit of n-of-1 trials to medical practice, perhaps asking a patient to try a pill and a placebo, and then report how they feel.
“What we’d really like to see is that you could actually do this study for individual patients as part of their care,” he said.