Which statin (HMG-CoA reductase inhibitor) has the lowest incidence of myalgia (muscle pain)?

From the Guidelines

Pitavastatin (Livalo) generally has the lowest incidence of muscle pain among statins. This is based on the most recent evidence from the 2022 ACC expert consensus decision pathway on the role of nonstatin therapies for LDL-cholesterol lowering in the management of atherosclerotic cardiovascular disease risk 1. According to this study, the predominantly hydrophilic statins, such as rosuvastatin and pravastatin, are less likely to cause muscle-related side effects compared to lipophilic statins like simvastatin, fluvastatin, pitavastatin, lovastatin, and atorvastatin. However, pitavastatin is considered to have a lower incidence of muscle pain among statins.

Some key points to consider when prescribing statins to minimize the risk of muscle pain include:

• Avoiding complete discontinuation of statin treatment is strongly recommended for patients with statin-associated muscle symptoms (SASEs) who meet evidence-based guideline criteria for statin therapy 1
• Clinicians should strive to find the highest tolerated statin dose that is as close to the guideline recommendation as possible and work with patients to help understand the nature and severity of symptoms 1
• Alternative statin regimens, such as alternate-day dosing with a long half-life statin (atorvastatin or rosuvastatin), de-escalation dosing, or a lower daily dose, may be considered for patients who experience SASEs 1
• Nonstatin therapies, such as ezetimibe or a PCSK9 mAb, may be considered as first-line therapy for patients with clinical ASCVD and possible SASEs who have failed at least 2 (and preferably 3) statins, including a trial of 1 attempt at the lowest approved dose or using alternative statin dosing 1

In terms of specific statins, fluvastatin (Lescol) and pravastatin (Pravachol) are also considered less likely to cause muscle-related side effects compared to more potent statins like atorvastatin (Lipitor) or simvastatin (Zocor) 1. However, the most recent evidence suggests that pitavastatin (Livalo) has the lowest incidence of muscle pain among statins. If a patient experiences muscle pain with one statin, switching to pitavastatin, fluvastatin, or pravastatin at a lower dose with gradual titration may help. Additionally, taking the medication in the morning rather than evening, ensuring adequate vitamin D levels, and avoiding certain interacting medications (like grapefruit juice or certain antibiotics) can further reduce the risk of muscle-related side effects while still providing cardiovascular benefits.

From the Research

Statin-Associated Myalgia

• The incidence of myalgia (muscle pain) varies among different statins, with some studies suggesting that hydrophilic statins may have a lower risk of muscular events compared to lipophilic statins 2.
• However, a study published in the Journal of General Internal Medicine found that the risk of muscular events was not significantly lower for hydrophilic statins (pravastatin and rosuvastatin) compared to lipophilic statins (simvastatin and atorvastatin) at comparable lipid-lowering doses 2.
• Another study published in Expert Review of Clinical Pharmacology noted that the evidence for muscle pain caused by statins is often equivocal and not particularly strong, and that reported symptoms are difficult to quantify 3.
• A review of pharmacological interactions of statins published in Atherosclerosis Supplements suggested that some statins, such as fluvastatin and pravastatin, may have a lower potential for adverse drug interactions due to their metabolic pathways 4.

Comparison of Statins

• A study published in Clinical Pharmacokinetics found that simvastatin and lovastatin, which are metabolized through cytochrome P450 (CYP) 3A, have a higher potential for drug-drug interactions with potent CYP3A inhibitors, and their coadministration is contraindicated 5.
• Atorvastatin, which is also a CYP3A substrate, has been reported to have less potent drug-drug interactions with CYP3A inhibitors 5.
• Pravastatin, which is eliminated through other metabolic routes, has been found to have a favorable safety profile in long-term clinical research trials, with a low incidence of musculoskeletal pain 6.

Incidence of Myalgia

• The incidence of myalgia associated with different statins is not well established, and more research is needed to determine which statin has the lowest incidence of myalgia.
• However, based on the available evidence, pravastatin may be associated with a lower incidence of myalgia due to its favorable safety profile and lower potential for adverse drug interactions 2, 4, 6.