Guideline sources The following summarized guidelines for the evaluation and management of statin-induced myopathy are prepared by our editorial team based on guidelines from the Baveno VII Consensus Workshop (Baveno VII 2022), the American College of Preventive Medicine (ACPM/ADA/PCNA/ABC/ASPC/AAPA/AGS/AHA/ACC/APhA 2019), the Canadian Cardiovascular Society (CCS 2016), and the American Heart Association (AHA/ACC 2014). 1 2 3 4 Guidelines 1. Screening and diagnosis Screening for adverse effects: As per AHA 2019 guidelines, assess appropriate safety indicators 4-12 weeks after statin initiation or dose adjustment and every 3-12 months thereafter based on the need to assess safety. A As per CCS 2016 guidelines, assess all purported statin-associated symptoms systematically, incorporating observation during cessation and reinitiation (same or different statin, same or lower potency, same or decreased frequency of dosing), to identify a tolerated, statin-based therapy for chronic use. B https://web.pathway.md/diseases/recZ1qDuUdXSW2M4E 1/4 6/24/23, 3:14 PM Statin-induced myopathy Pathway As per ACC 2014 guidelines, do not measure CK levels routinely in patients on statin therapy. D 2. Diagnostic investigations Clinical assessment: As per AHA 2019 guidelines, obtain a thorough assessment of symptoms in patients with statin- associated muscle symptoms, in addition to an evaluation for non-statin causes and predisposing factors. A As per ACC 2014 guidelines, consider evaluating for non-statin causes (such as exposure to other drugs, systemic or neuropsychiatric causes), in addition to the possibility of adverse effects associated with statin drug therapy, in patients presenting with a confusional state or memory impairment while on statin therapy. C Laboratory tests: As per AHA 2019 guidelines, measure CK levels in patients with severe statin-associated muscle symptoms and objective muscle weakness. Measure liver transaminases (AST, ALT), TBIL, and ALP in patients with symptoms suggesting hepatotoxicity. B As per ACC 2014 guidelines, consider measuring CK levels in patients with muscle symptoms, including pain, tenderness, stiffness, cramping, weakness, or generalized fatigue, occurring during statin therapy. C Show 4 more 3. Medical management Treatment modifications: As per AHA 2019 guidelines, switch to moderate-intensity statin therapy with the aim of achieving a 30-49% reduction in LDL cholesterol levels in patients with clinical ASCVD experiencing statin-associated side effects on high-intensity statin therapy. A Show 3 more As per ACC 2014 guidelines, consider managing muscle symptoms, including pain, tenderness, stiffness, cramping, weakness, or fatigue, in statin-treated patients according to the following management strategy: Situation Guidance Discontinue statins promptly in patients developing unexplained severe muscle symptoms or fatigue, and obtain an evaluation for rhabdomyolysis Severe symptoms Discontinue statins until the symptoms can be evaluated in patients developing mild-to- Resolving mild-to-moderate symptoms https://web.pathway.md/diseases/recZ1qDuUdXSW2M4E 2/4 6/24/23, 3:14 PM Statin-induced myopathy Pathway moderate muscle symptoms Resume the original or a lower dose of the same statin, if not contraindicated, to establish a causal relationship between muscle symptoms and statin therapy if mild- to-moderate symptoms resolve after statin discontinuation Discontinue the original statin if a causal relationship exists Switch to a low dose of a different statin once muscle symptoms resolve Increase the dose gradually as tolerated once low-dose statin is tolerated Consider evaluating for other causes of muscle symptoms if muscle symptoms or elevated CK levels do not resolve completely after 2 months without statin treatment Non-resolving mild-to-moderate symptoms Resume statin therapy at the original dose if persistent muscle symptoms are determined to arise from a condition unrelated to statin therapy or if the predisposing condition has been treated. C Non-statin causes 4. Specific circumstances Patients with chronic liver disease: As per Baveno VII 2022 guidelines: Prescribe statins at a lower dose (such as simvastatin at a maximum of 20 mg/day) in patients with Child-Pugh B and C cirrhosis, and obtain close monitoring for muscle and liver toxicity. A Restrict the use of statins in patients with Child-Pugh C cirrhosis since their benefit in these patients has not been proven yet. B As per AHA 2019 guidelines, consider obtaining baseline measurements and determining a schedule of monitoring and safety checks before initiating statins in patients at increased ASCVD risk with chronic, stable liver disease (including non-alcoholic fatty liver disease). B 5. Preventative measures Pretreatment assessment: https://web.pathway.md/diseases/recZ1qDuUdXSW2M4E 3/4 6/24/23, 3:14 PM Statin-induced myopathy Pathway As per AHA 2019 guidelines: Conduct a clinician-patient risk discussion before initiating statin therapy to review net clinical benefit, weighing the potential for ASCVD risk reduction against the potential for statin- associated side effects, drug-drug interactions, and safety while emphasizing that side effects can be addressed successfully, A as well as to promote shared decision-making taking into account patient preferences. B Identify potential predisposing factors for statin-associated side effects, including new-onset diabetes mellitus and statin-associated muscle symptoms, before initiating statin therapy. B As per ACC 2014 guidelines, elicit a history of prior or current muscle symptoms to establish a baseline before initiating statin therapy. B Show 4 more References 1. Scott M Grundy, Neil J Stone, Alison L Bailey et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Blood Cholesterol: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines. Circulation. 2019 Jun 18;139 25):e1082-e1143. Open 2. Stone NJ, Robinson JG, Lichtenstein AH et al. 2013 ACC/AHA guideline on the treatment of blood cholesterol to reduce atherosclerotic cardiovascular risk in adults: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2014 Jul 1;63 25 Pt B 2889 934. Open 3. Anderson TJ, Gr goire J, Pearson GJ et al. 2016 Canadian Cardiovascular Society Guidelines for the Management of Dyslipidemia for the Prevention of Cardiovascular Disease in the Adult. Can J Cardiol. 2016 Nov;32 11 1263 1282. Open 4. Roberto de Franchis, Jaime Bosch, Guadalupe Garcia-Tsao et al. Baveno VII Renewing consensus in portal hypertension. J Hepatol. 2022 Apr;76 4 959 974. Open https://web.pathway.md/diseases/recZ1qDuUdXSW2M4E 4/4