From the FDA Drug Label
Atorvastatin calcium may cause myopathy (muscle pain, tenderness, or weakness associated with elevated creatine kinase [CK]) and rhabdomyolysis. Risk factors for myopathy include age 65 years or greater, uncontrolled hypothyroidism, renal impairment, concomitant use with certain other drugs (including other lipid-lowering therapies), and higher atorvastatin calcium dosage Atorvastatin calcium exposure may be increased by drug interactions due to inhibition of cytochrome P450 enzyme 3A4 (CYP3A4) and/or transporters (e.g., breast cancer resistant protein [BCRP], organic anion-transporting polypeptide [OATP1B1/OATP1B3] and P-glycoprotein [P-gp]), resulting in an increased risk of myopathy and rhabdomyolysis.
The exact mechanism of why bempedoic acid and statins (HMG-CoA reductase inhibitors) cause myalgia (muscle pain) is not directly stated in the provided drug label. However, the label suggests that myopathy and rhabdomyolysis associated with statin use, including atorvastatin, may be related to:
- Elevated creatine kinase (CK) levels
- Drug interactions that increase atorvastatin exposure
- Concomitant use with certain other drugs, including other lipid-lowering therapies
- Higher atorvastatin calcium dosage
- Risk factors such as age, uncontrolled hypothyroidism, and renal impairment 1
From the Research
Bempedoic acid and statins can cause muscle pain primarily due to their effects on the mevalonate pathway, though they act at different points, with bempedoic acid typically causing less muscle pain than statins due to its primary action in the liver rather than muscle tissue, as supported by a study published in 2024 2. The mechanism of action of these drugs is key to understanding their side effects. Statins inhibit the enzyme HMG-CoA reductase, which is an early step in cholesterol synthesis, reducing cholesterol production and also decreasing production of other important compounds like coenzyme Q10 and isoprenoids, essential for muscle cell function and mitochondrial energy production, as discussed in a study from 2022 3. Bempedoic acid works upstream of statins by inhibiting ATP-citrate lyase, which ultimately affects the same pathway but is primarily active in the liver rather than muscle tissue, as explained in a study from 2020 4. Some key points to consider include:
- The severity of muscle pain can range from mild discomfort to severe myopathy, with the risk increasing at higher doses and with certain drug interactions.
- Genetic factors play a role in determining who experiences these side effects, as variations in genes related to drug metabolism and muscle function can increase susceptibility to muscle symptoms.
- Bempedoic acid has been shown to be a safe and effective alternative to statins in high-risk patients intolerant to statins, decreasing the risk of major adverse cardiovascular events (MACE), as demonstrated in a systematic review and meta-analysis from 2024 2.
- The incidence of myalgia was reduced in the bempedoic acid group compared to placebo, as reported in a study from 2019 5. Overall, the choice between bempedoic acid and statins should be based on individual patient factors, including their risk of cardiovascular events, history of muscle symptoms, and genetic predispositions, with the goal of minimizing morbidity, mortality, and improving quality of life, as supported by the most recent and highest quality study available 2.