What statin (3-hydroxy-3-methylglutaryl-coenzyme A reductase inhibitor) therapy is associated with the lowest risk of myalgias (muscle pain)?

From the Guidelines

Pitavastatin is associated with the lowest risk of myalgias among statin medications, with muscle-related symptoms occurring in only 2.3% of patients in the REPRIVE trial 1. When considering statin therapy, it is essential to evaluate the risk of myalgias, as this side effect can impact patient adherence and quality of life. The choice of statin can significantly influence the risk of myalgias, with some statins having a lower propensity for causing muscle pain. Key factors to consider when selecting a statin include the patient's individual risk factors, such as age, sex, body mass index, and comorbidities, as well as the statin's pharmacokinetic properties, including its hydrophilicity and metabolism. According to the 2024 recommendations on the optimal use of lipid-lowering therapy, pitavastatin is a potent inhibitor of HMG-coenzyme A reductase with a favorable side effect profile, including a low risk of myalgias 1. In contrast to other statins, pitavastatin does not increase the risk of new-onset diabetes and has a beneficial effect on fasting blood glucose and HbA1c levels 1. The REPRIVE trial demonstrated the efficacy and safety of pitavastatin in reducing major adverse cardiovascular events, with a significant reduction in muscle-related symptoms compared to placebo 1. Overall, pitavastatin is a rational treatment choice for patients with metabolic disturbances, diabetes, or pre-diabetes, and its use can help minimize the risk of myalgias and improve patient adherence to statin therapy. It is crucial to individualize statin therapy based on patient-specific factors, including the risk of myalgias, to optimize treatment outcomes and improve quality of life. In patients who experience myalgias with other statins, switching to pitavastatin may be beneficial, and alternative dosing strategies, such as every-other-day or twice-weekly regimens, can also be considered to minimize muscle symptoms. Coenzyme Q10 supplementation may also be helpful in managing statin-associated muscle pain, although the evidence for this approach is mixed 1. Ultimately, the selection of a statin should be based on the individual patient's needs and risk factors, with pitavastatin being a viable option for those at risk of myalgias. The 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the management of blood cholesterol also emphasizes the importance of evaluating musculoskeletal symptoms and predisposing factors for statin-associated muscle symptoms before initiating statin therapy 1. By carefully considering these factors and selecting the most appropriate statin, healthcare providers can help minimize the risk of myalgias and optimize treatment outcomes for patients with hyperlipidemia. In clinical practice, it is essential to monitor patients for signs and symptoms of myalgias and adjust statin therapy accordingly to ensure the best possible outcomes. The use of pitavastatin, with its favorable side effect profile and low risk of myalgias, can be an effective strategy for minimizing muscle-related symptoms and improving patient adherence to statin therapy. By prioritizing patient-centered care and individualizing statin therapy, healthcare providers can help patients achieve optimal lipid control while minimizing the risk of adverse effects. The evidence from recent studies, including the REPRIVE trial, supports the use of pitavastatin as a first-line statin for patients at risk of myalgias, and its use can be considered in conjunction with other lipid-lowering therapies to achieve optimal treatment outcomes. In summary, pitavastatin is a rational treatment choice for patients with hyperlipidemia who are at risk of myalgias, due to its favorable side effect profile and low risk of muscle-related symptoms 1.

From the Research

Statin Therapy with Least Myalgias

• The statin therapy associated with the lowest risk of myalgias is pitavastatin, as demonstrated in a case report where a patient developed bilateral myalgia with fluvastatin, pravastatin, and a combination of atorvastatin and ezetimibe, but tolerated a combination of pitavastatin and ezetimibe 2.
• Pitavastatin has shown less potential for the development of myalgia compared to other statins, such as fluvastatin and pravastatin, which were previously considered to be the most tolerable statins.
• The combination of pitavastatin and ezetimibe appears to be a promising treatment choice for individuals who are intolerant to statin therapy due to muscle complaints.

Coenzyme Q10 Supplementation

• Coenzyme Q10 (CoQ10) supplementation has been studied as a potential treatment for statin-associated myalgia, but the evidence is limited and conflicting.
• Several studies have found no benefit of CoQ10 supplementation in improving myalgia symptoms or improving adherence to statin therapy 3, 4, 5.
• A systematic review and meta-analysis found that CoQ10 supplementation did not demonstrate any benefit in improving myalgia symptoms or improving adherence to statin therapy 4.
• Another study found that CoQ10 did not produce a greater response than placebo in the treatment of presumed statin-induced myalgias 5.

Comparison of Statins

• The available evidence suggests that pitavastatin may be associated with a lower risk of myalgias compared to other statins, such as fluvastatin, pravastatin, and atorvastatin 2.
• However, more research is needed to confirm these findings and to compare the risk of myalgias associated with different statins.
• The choice of statin should be individualized based on the patient's specific needs and medical history, and patients who experience myalgias with one statin may be able to tolerate another statin.