Statin-Associated Side Effects (SASE) Statin-Associated Side Effects Frequency Predisposing Factors Quality of Evidence Statin-associated muscle symptoms (SAMS) Myalgias (CK normal) Infrequent (1% to 5%) in RCTs; frequent (5% to 10%) in observational studies and clinical setting Age, female sex, low body mass index, high-risk medications (CYP3A4 inhibitors, OATP1B1 inhibitors), comorbidities (HIV, renal, liver, thyroid, preexisting myopathy), Asian ancestry, excess alcohol, high levels of physical activity, and trauma RCTs cohorts/ observational Myositis/myopathy (CK > ULN) with concerning symptoms or objective weakness Rare RCTs cohorts/ observational Rhabdomyolysis (CK >10 ULN + renal injury) Rare RCTs cohorts/ observational Statin-associated autoimmune myopathy (HMGCR antibodies, incomplete resolution) Rare Case reports New-onset diabetes mellitus Depends on population; more frequent if diabetes mellitus risk factors are present, such as body mass index 30, fasting blood glucose 100 mg/dL; metabolic syndrome, or A1c 6%. Diabetes mellitus risk factors/metabolic syndrome RCTs/meta-analyses High-intensity statin therapy Liver Transaminase elevation 3 ULN Infrequent RCTs/cohorts/ observational Case reports Hepatic failure Rare Central nervous system Memory/cognition Rare Case reports; no increase in memory/ cognition problems in 3 large-scale RCTs Cancer No definite association RCTs/meta-analyses Other Renal function Unfounded Cataracts Unfounded Tendon rupture Unfounded Hemorrhagic stroke Unfounded Interstitial lung disease Unfounded Low testosterone Unfounded CK indicates creatine kinase; HIV, human immunodeficiency virus; HMGCR, 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase; SAMS, statin-associated muscle symptoms; SAAM, statin-associated autoimmune myopathy; SASE, statin associated side effects; and ULN, upper limit of normal. CLINICAL STATEMENTS AND GUIDELINES (myopathy) and associated significant increase in CK (myositis) are rareS5-1,S5-22,S5-30 but require prompt statin cessation and evaluation for reversible causes. Rhabdomyolysis (CK >10 times upper limit of normal, with evidence of renal injury) is exceed- ingly rare and usually encountered in the setting of a patient with several predisposing comorbidities and concomitant high-risk medications.S5-1,S5-22,S5-30 It requires immediate medical attention. 3. 