If you or someone you know has experienced side effects from a cholesterol medication, a recent mouse study published in Journal of Clinical Investigation may have answers. Scientists point out how, despite being among the most commonly prescribed drugs and treatments for high cholesterola significant proportion of people are intolerant to statins. While many are prescribed the drugs without problems, about 10 percent of users develop painful side effects known as statin-associated muscle symptoms, or SAMS, which lead to muscle pain. Historically, the reason for SAMS has been unclear. Now scientists say they have discovered a potential cause of the painful symptoms associated with statins, which may lead to breakthroughs in limiting these side effects.
Meet the experts: Catherine Benziger, MDmember of the American College of Cardiology Cardiovascular Disease Prevention Council; Cheng-Han Chen, MDboard-certified interventional cardiologist and medical director of the Structural Heart Program at MemorialCare Saddleback Medical Center in Laguna Hills, CA
Researchers believe they have identified a reasonable mechanistic explanation for 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 genetic 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, where one group contained wild-type or non-genetically modified mice and the other contained mice with the genetic mutation. After giving both groups a type of statin, simvastatin, the researchers found that the group with the mutation was more prone to SAMS due to the influx of calcium into the muscle cells.
Next, we spoke to cardiologists to reveal the findings and their implications.
Why are the findings significant?
While the side effects of taking statins can leave some users intolerant to the drug class, the drug 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 blows“, he explains Catherine Benziger, MDmember of the American College of Cardiology Prevention of Cardiovascular Diseases. “But I see many patients who complain of muscle pain and cramps after starting a statin in my clinic. . . . Sometimes it’s minor and the medication can be continued, but other times it’s severe and the medication has to be stopped.”
“Muscle symptoms associated with statins are the most common reason people stop taking statins,” he says Cheng-Han Chen, MDboard-certified interventional cardiologist and medical director of the Structural Heart Program at MemorialCare Saddleback Medical Center in Laguna Hills, CA. “A better understanding of what causes these symptoms can help us find ways to reduce these effects and help patients 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 supported by basic science and clinical research, it’s easier to counsel patients and educate them about the side effects it might cause,” she explains. “It may also improve our knowledge of who might be more likely to be affected, particularly those with genetic mutations, and how we can prevent them.”
Not only do the findings show that a genetic mutation can cause SAMS, but also “that a drug that targeted this mutation could prevent the symptoms,” adds Dr. Chen. This “could help us treat these side effects and help patients stay on the statins they need.”
What does this mean to you?
If you start a statin or are already taking one, don’t stop. It is important to monitor any side effects you have closely and report them to your doctor. “If a patient has muscle side effects, I tell them [them] stop taking the statin for five to seven days and make sure the muscle side effects go away, then restart it,” says Dr. Benziger. If symptoms return, she advises working with your doctor to switch to a different strain or reduce the dose.
Are there alternatives to statins?
In many cases, side effects resolve with switching to a different strain, according to Dr. Chen. However, some people may not be able to tolerate statins at all. That doesn’t mean you should stop treatment entirely, warns Dr. Benziger. “The key is to reach your LDL goal! It’s extremely important not to overlook cholesterol management, especially in someone who has diabetes, kidney disease, a history of heart disease, an elevated coronary artery calcium score, or other risk factors.” If you can’t tolerate statins, Dr. Chen and Dr. Benziger suggest working with your doctor to find an alternative drug, such as a PCSK9 inhibitor or bempedoic acid.
The bottom line
While the biological mechanism revealed by these results offers promising new insight into why some statin users experience SAMS, there is still much we do not know. “These findings were only studied in a mouse model. Future research will be needed to determine whether the findings translate to humans,” Dr. Chen points out.
However, 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 might reduce these side effects or lead to improved treatments without this limitation.”
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