2023 Hellenic Atherosclerosis Society guidelines for management of Statin-associated muscle symptoms

Statin-associated muscle symptoms (SAMS) are the most commonly encountered side effects of statin therapy, which could result in discontinuation of the medication and increases the risk of recurrent cardiac events. The most frequent type of SAMS are muscle pains with or, most commonly, without creatine kinase elevation. These are dose-dependent and appear independent of LDL-C reduction.

Several ways to manage the patient with SAMS are:

• Re-evaluate the requirement of statin therapy.
• Assure the patient that muscle complaints are reversible and that statins are extremely safe and effective medications.
• Make drastic lifestyle adjustments
• Get rid of contributory variables, such as vitamin D insufficiency, hypothyroidism, and other medications that might interact with statins. 
• Verify the diagnosis
• Dechallenge: discontinue statin and wait (usually 4–6 weeks) until complete resolution of symptoms + normalization of CK
• Rechallenge: try a second (usually different) statin at low dose (after dechallenge). If this is tolerated:
• Statin can be up-titrated to achieve LDL-C goal, or as much LDL-C reduction can be achieved with minimal muscle complaints, or
• Statin remains at low or moderate dose and ezetimibe is added.
• If a second statin causes recurrence of muscle symptoms, try low dose of atorvastatin (5–10 mg) or rosuvastatin (5 mg) on alternate days or twice weekly. This method reduces LDL-C by 25–35% and is well tolerated by most statin-intolerant individuals (about 80%). Ezetimibe should be taken with statins to further lower LDL-C.
• No further statin attempts should be made if the patient is intolerant to the third introduction of the medication or if the alternate low dose is not tolerated.
• In statin-intolerant patients, consider:
• Ezetimibe and
• APCSK9 inhibitor (alirocumab or evolocumab) if, despite low statin dose (in partially intolerant patients) + ezetimibe, LDL-C remains >100 mg/dL in patients with established cardiovascular disease or >130 mg/dL in high-risk patients
• Bempedoic acid is an alternative to statin treatment in patients with SAMS.

Source: Katsiki N, Filippatos T, Vlachopoulos C, Panagiotakos D, Milionis H, Tselepis A, Garoufi A, Rallidis L, Richter D, Nomikos T, Kolovou G, Kypreos K, Chrysohoou C, Tziomalos K, Skoumas I, Koutagiar I, Attilakos A, Papagianni M, Boutari C, Kotsis V, Pitsavos C, Elisaf M, Tsioufis K, Liberopoulos E. Executive summary of the Hellenic Atherosclerosis Society guidelines for the diagnosis and treatment of dyslipidemias - 2023. Atheroscler Plus. 2024 Feb 17;55:74-92. doi: 10.1016/j.athplu.2024.01.004. PMID: 38425675; PMCID: PMC10901915.