If you or someone you know has experienced side effects from a cholesterol medication, a recent mouse study published in the Journal of Clinical Investigation may have answers. Scientists outline how, despite being among the most frequently prescribed drugs and treatments for high cholesterol, a significant portion of people are intolerant to statins. While many are prescribed the medication with no issues, about 10% of users develop painful side effects known as statin-associated muscle symptoms, or SAMS, which leads to muscle soreness. Historically, the reason for SAMS has been unclear. Now, scientists say they have uncovered a potential cause for the painful symptoms associated with statins, which may lead to breakthroughs to limit these side effects.
Meet the experts: Catherine Benziger, M.D., member of the American College of Cardiology Prevention of Cardiovascular Diseases Council; Cheng-Han Chen, M.D., board-certified interventional cardiologist and medical director of the Structural Heart Program at MemorialCare Saddleback Medical Center in Laguna Hills, CA
The researchers believe they identified a reasonable mechanical explanation as to why some experience muscle weakness, aches, and pains while taking statins. The study revealed that the culprit may not be the drug itself, but rather a gene mutation that affects skeletal muscle receptors, and in turn, leads to changes in calcium release when statins are introduced into the system.
The study was conducted using a mouse model, in which one group contained wild-type, or genetically unmodified, mice, and the other contained mice with the genetic mutation. After administering one type of statin, simvastatin, to both groups, the researchers found that the group with the mutation was more prone to SAMS due to an influx of calcium into muscle cells.
Ahead, we spoke to cardiologists to break down the findings and their implications.
Why are the findings significant?
While side effects from statin use may leave some users intolerant to the drug class, the medication remains one of the most effective ways to lower LDL (or “bad”) cholesterol levels, so it’s important to understand why some patients may experience these symptoms. “Statins are an incredibly effective and proven therapy to lower cholesterol and reduce the risk of heart attacks and strokes,” explains Catherine Benziger, M.D., member of the American College of Cardiology Prevention of Cardiovascular Diseases Council. “But I see many patients who complain of muscle aches and cramps after starting a statin in my clinic…Sometimes this is minor, and the medication can be continued, but other times it is severe, and the medication must be stopped.”
“Statin-associated muscle symptoms are the most common reason people stop their statins,” says Cheng-Han Chen, M.D., board-certified interventional cardiologist and medical director of the Structural Heart Program at MemorialCare Saddleback Medical Center in Laguna Hills, CA. “Better understanding the cause of these symptoms can potentially help us find ways to reduce these effects and help patients to stay on these important medications.”
The study’s findings are significant in that they identify a specific biological mechanism that may be responsible for SAMS, according to Dr. Benziger. “When a mechanism is backed up by basic science and clinical research, it makes it easier to counsel patients and educate them about what the side effects they have might be caused by,” she explains. “It also can improve our knowledge of who might be more likely to be affected, specifically those with genetic mutations, and how we can possibly prevent them.”
Not only do the findings reveal that a genetic mutation may cause SAMS, but also “that a drug that targeted this mutation could prevent the symptoms,” Dr. Chen adds. This “could potentially help us treat these side effects and help patients stay on the statins that they need.”
What does this mean for you?
If you’re starting a statin or are already taking one, don’t stop. It’s important to closely monitor any side effects you experience and communicate them to your doctor. “If a patient has muscle side effects, I tell [them] to stop taking the statin for five to seven days and make sure the muscle side effects go away, and then restart it,” says Dr. Benziger. If the symptoms return, she advises working with your doctor to switch to a different strain or decrease the dose.
Are there alternatives to statins?
In many cases, side effects resolve once switching to a different strain, according to Dr. Chen. Still, some people may not be able to tolerate statins at all. That doesn’t mean you should stop treatment entirely, Dr. Benziger warns. “The key is getting the LDL to goal! It is critically important not to overlook managing cholesterol, particularly in someone who has diabetes mellitus, kidney disease, a history of heart disease, an elevated coronary artery calcium score, or other risk factors.” If you’re unable to tolerate statins, Dr. Chen and Dr. Benziger suggest working with your doctor to find an alternative medication, such as a PCSK9 inhibitor or bempedoic acid.
The bottom line
While the biological mechanism revealed by these results offers a promising new look into why some statin users experience SAMS, there’s still a lot we don’t know. “These findings have only been studied in a mouse model. Future research will be needed to determine whether the findings translate to humans as well,” Dr. Chen points out.
Still, if future research further validates these findings and proves they can be replicated, Dr. Benziger is optimistic that those who are eligible to take statins for high cholesterol will benefit, as the findings “[offer] a hypothesis for future therapies that could reduce these side effects or lead to improved treatments without this limitation.”
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