Cholesterol is a major risk factor for heart disease and stroke, which causes nearly 1 in 3 deaths among Americans. Too much cholesterol in the blood causes plaque (cholesterol deposits) buildup in the walls of the arteries. Plaque buildup can harden or clog the arteries and reduce blood flow to the heart. As a result, a person experiences chest pain, shortness of breath, and a heart attack.
Statin-induced myopathy is an adverse effect of undergoing statin treatment characterized by muscle weakness and pain, resulting in difficulty in performing daily life activities.
Uncontrolled cholesterol levels due to statin discontinuation can result in drastic cardiovascular consequences and mortality.
Rosuvastatin 10 mg and Fluvastatin XL 80 mg have the lowest incidences of myopathy induction with 10.8% and 8%, respectively, compared to 50% from Simvastatin 40 mg.
Muscular symptoms from statin-induced myopathy can be ameliorated by some treatment strategies, including a modified treatment regimen, diet and lifestyle changes, and CoQ10 supplementation.
To lower cholesterol levels and risks of cardiovascular complications, doctors prescribe statins. Unfortunately, statins can induce a side effect called myopathy, the weakness of muscular tissues. Here, we discuss statin-induced myopathy and potential treatments to relieve this adverse effect.
What are Statins?
Statins are a class of drugs that effectively lower the blood level of low-density lipoprotein (LDL) cholesterol, otherwise known as the “bad” cholesterol. Statins are also known as 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR) inhibitors. They work by inhibiting cholesterol production in the liver. With statins, the risks of stroke, heart attack, and even death from cardiovascular disease are significantly lowered.
However, statins can cause side effects. Some are common, while some are rare. The following are potential side effects caused by statins:
- nausea or vomiting
- sleep problems
- bloating or gas
- liver inflammation
- low platelet count
- muscle pain
- muscle weakness
What is Myopathy?
The National Institute of Neurological Disorders and Stroke (NINDS). under the National Institutes of Health (NIH). defines myopathy as a neuromuscular disorder characterized by muscle weakness as the primary symptom. Myopathy is due to muscular dysfunction – specifically, the muscle fibers do not function properly, resulting in muscular weakness. It may also include muscle stiffness, spasm, and cramps.
Myopathy affects muscle structure, metabolism, or physiological functions. Depending on risk factors, myopathy can present with mild discomfort or severe enough pain to interfere with daily life activities. Myopathy primarily afflicts the voluntary muscles needed to perform movements, so patients with myopathy experience difficulty even in simple tasks such as taking a bath, walking, or standing up from bed.
What is statin-induced myopathy?
According to the American College of Cardiology, statin-induced myopathy is the most common complaint of patients undergoing statin treatment. In general, around 27.8% of patients taking statins develop myopathy. When patients develop myopathy, they experience muscle-related symptoms that didn’t exist before they started statin treatment.
Statins are generally safe and well tolerated, but they are also associated with undesirable side effects. The following are the symptoms of statin-induced myopathy:
- muscle pain, tenderness, or weakness
- muscle cramps or leg cramps, especially at night
- muscle stiffness or spasms
On the other hand, here are the most important risk factors that increase the likelihood of statin-induced myopathy:
- Advanced age (80 and above).
- Female sex.
- Low (BMI) body mass index.
- Having multisystem disease, involving the liver, kidney, or both.
- High consumption of grapefruit juice (>1 quart/day).
- Hypothyroidism (underactive thyroid).
- Alcohol use disorder (too much alcohol consumption).
- Diagnosed with type 1 or 2 diabetes.
- Have undergone major surgery.
- Performing excessive physical activity.
- Family history or previous myopathy experience with other cholesterol-lowering drugs.
- Have a history of elevated blood creatine kinase level.
- Undetermined cause of cramps.
- Receiving high-dose statin treatment.
Polypharmacy or drug interaction with other drugs concurrently taken, including.
- HIV protease inhibitors
- Macrolide inhibitors
Statins can contribute to the development of myopathies (myalgia, myositis, and rhabdomyolysis) by impairing muscle cell functions leading to muscle breakdown. Blood levels of creatine kinase, an enzyme associated with muscle damage, are indicative of myopathy severity.
Based on severity, myopathy can be classified into three categories: myalgia, myositis, and rhabdomyolysis.
Myalgia – Myalgia is the medical term for general muscle pain. Muscle symptoms may include spasms, tenderness, or weakness. Myalgia has no creatine kinase elevation.
Myositis – Myositis has increased levels of creatine kinase, typically less than 10 times the upper limit of normal blood levels.
Rhabdomyolysis – Rhabdomyolysis is rare, but the most life-threatening form of myopathy, accompanied by severe muscle pain and weakness throughout the body, dark urine, and even kidney damage. It is characterized by highly elevated creatine kinase in the blood and myoglobinuria (excess myoglobin amounts in urine). Typically, creatine kinase is more than 10 times the upper limit of normal blood levels.
Statin-induced necrotizing myopathy is a rare complication associated with high creatine kinase levels, which may occur during statin treatment and persist even after cessation of therapy. Additionally, statin-induced necrotizing myositis can develop with the muscle cells also undergoing cell death or necrosis. Muscle biopsies of necrotizing myopathies show that there’s a low level of inflammation, but high levels of necrosis or muscle cell death.
Some data also suggest that statins can trigger overexpression of the HGMCR on muscle cells and cause necrotizing myopathy/myositis due to the attack of anti-HGMCR antibodies, triggering an autoimmune response in genetically susceptible patients. This response can lead to severe, progressive muscle weakness observed in necrotizing myopathies.
Why do statins cause myopathy?
The exact molecular mechanism of how statins induce myopathy is not fully understood. Studies have demonstrated several mechanisms that impair critical molecular functions related to muscle physiology.
Research findings suggest that statins can:
Reduce levels of coenzyme Q10 (coQ10), an essential nutrient in the mitochondrial generation of energy
Exist in lactone form, the non-therapeutic form, once inside the body, which can also impair mitochondria function leading to low energy
Promote leakage of calcium reserves from the muscle which may ultimately cause muscle pain and weakness
Others have hypothesized about the muscle damage and destruction of muscle cells. Nonetheless, the incidence of myopathy caused by statins differs depending on the statin used.
Which statin is less likely to cause muscle pain?
According to this 2022 study of statin therapy that followed up the patients for 12 months, myopathy was observed highest with Simvastatin 40 mg – around 50% of patients developed myopathy.
The lowest incidences of myopathy were observed with Rosuvastatin 10 mg and Fluvastatin XL 80 mg, wherein only 10.8% and 8% of the patients developed myopathy, respectively.
For the other statins, the incidences of myopathy are as follows:
- Rosuvastatin 20 mg – 14.6%
- Atorvastatin 10 mg – 12.5%, 20 mg – 21.2%, 40 mg – 28.9%
- Simvastatin 20 mg – 25.3%
Will the muscle pain go away?
Symptoms of statin-related muscle pain start to show soon after beginning treatment. Generally speaking, within a month or the first few months after starting statin treatment, patients susceptible to myopathy experience weak or achy muscles in their arms, shoulders, lower back, thighs, or buttocks.
In the majority of patients, muscle aches go away on their own after the first few weeks of statin medication. If a statin medication user stops taking statins, muscle pain usually resolves within 1–2 weeks.
Statin-induced myopathy treatment
Statins are important drugs to bring down elevated LDL levels and cut the risks of cardiovascular disease and mortality. However, due to adverse effects like myopathy, patients may opt to stop their statin treatment, which can lead to drastic consequences. Some treatments can help manage statin-induced myopathy; the treatments vary depending on severity.
Once you experience muscle pain or weakness during your statin treatment, talk with your healthcare provider or doctor as soon as possible to help you manage the symptoms or rule out other underlying factors or conditions, while ensuring that your cholesterol levels get under control.
Here are some treatment strategies that are currently recommended to help relieve statin-induced myopathy that you may ask your doctor about:
- Lowering the dosage to the most effective amount.
- Switching to other statins with lower myopathy risks.
- Switching to non-statin cholesterol-lowering drugs.
- Temporarily halting statin (e.g., for 3–4 weeks) or taking a statin every other day.
- Reviewing your other medications and discussing potential interactions with statins.
- Supplementation with CoQ10 or Vitamin D.
- Implementing diet and lifestyle changes that may help.
- Engaging in regular, moderate exercise and avoiding intense physical activity.
- Getting a blood test for hypothyroidism
Recovering from statin-induced myopathy
Patients usually fully recover from statin-induced myopathy after stopping treatment within 3 months. However, for patients who need long-term statin treatment to manage their abnormal LDL levels, myopathy may persist but it can be controlled with the previously mentioned strategies and with doctors’ guidance. Recovery from statin-induced myopathy while managing cholesterol levels is also more likely if patients shift to non-statin lipid-lowering medications.
In very rare cases (estimated incidence of 2–3 cases in every 100,000), a patient may develop statin-induced necrotizing autoimmune myopathy (SINAM), a severe progressive muscle weakness, even after statins have been discontinued. This may require treatment with steroids and immunomodulatory drugs, but IVIG treatment has also been demonstrated to be successful. It is important to keep your doctor updated.