Disclosures. How do statins work? Statin Pharmacokinetics 9/12/2013 THERAPEUTIC INTERVENTIONS FOR STATIN INTOLERANT PATIENTS

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1 Disclosures Speakers Bureau- LipoScience Inc. THERAPEUTIC INTERVENTIONS FOR STATIN INTOLERANT PATIENTS Casey Elkins, DNP, NP-C, CLS How do statins work? Bays H, Stein EA. Expert Opin Pharmacother. 2003;4(11): Statin Pharmacokinetics According to the Prescribing Information Schachter M. Fundamental & Clinical Pharmacology 2005;1:

2 Statin Safety Muscle adverse effects Liver adverse effects Renal effects Cognitive effects New onset DM NLA Statin Safety Task Force Definitions of muscle symptoms Myalgia Muscle aches without CK elevations Myopathy Myalgia, + elevation of CK > 10x ULN Rhabdomyolysis CK > 10,000 IU/L, or CK > 10 x ULN plus an elevation of serum creatinine, or requiring IV hydration or medical intervention Incidence of Muscle Adverse Effects Muscle Adverse Effects Incidence Myalgia 1.5-3% Myopathy 5/100,000 Rhabdomyolysis 1.6/100,000 McKenney JM, Davidson MH, Jacobson TA, et al. The American Journal of Cardiology. Apr ;97(8A):89C-94C. Law M et al. Am J Cardiol. 2006; 97 (suppl 8A): 52C-61C. % of CK elevation > 10x ULN by statin dose Factors Increasing Risk for Muscle Symptoms Patient Characteristics Increasing age Female sex Renal insufficiency Hepatic dysfunction Hypothyroidism Polypharmacy Diet Statin Characteristics Higher statin dose Drug- drug interactions via CYP pathway Rosenson. Am J Med. 2004;116: Jacobson TA. Am J Cardiol. 2006; 97 (suppl 8A): 44C-51C. 2

3 Muscle Symptom Recommendations Management of Muscle Symptoms Rule out other secondary causes of myalgia Hypothyroidism Trauma Fall Seizure Increased physical activity Only check CK in symptomatic patients Consider exacerbating factors Grapefruit/Pomegranate juice Medication interactions McKenney JM et al. Am J Cardiol. 2006;97:89C-94C. Thompson PD et al. Am J Cardiol. 2006;97:69C-76C. Intolerable muscle symptoms: DC statin regardless of CK- Re challenge when asymptomatic Tolerable muscle symptoms: Mild CK elevation Continue statin use symptoms as a guide Tolerable muscle symptoms: Mod- Severe CK elevation DC statin Re challenge with lower dose or different statin McKenney JM et al. Am J Cardiol. 2006;97:89C-94C. Thompson PD et al. Am J Cardiol. 2006;97:69C-76C. Rhabdo: Don t throw the baby out with the bathwater!!! Management of Muscle Symptoms Alternate day dosing Low dose- High potency Hydrophilic vs. lipophilic Jacobson. TA Mayo Clin Proc 83(6): Liver Adverse Effects Progression to liver failure is extremely rare Idiopathic liver failure Statins do not worsen transaminase elevations associated with chronic liver disease Reduction of dose often reverses transaminase elevation Checking LFTs Cohen et al. Am J Cardiol. 2006; 97 (suppl 8A): 77C-81C. 3

4 Recommendations Other Adverse Effects Routine monitoring of LFTs is NOT necessary for patients on statins Monitor for signs of hepatotoxicity Use fractionated bilirubin to detect liver dysfunction If AST/ALT are 1-3x ULN do NOT discontinue If AST/ALT are > 3x ULN repeat labs and look for other causes Pts with chronic liver disease, NAFLD, & NASH can tolerate statins If objective evidence of liver dysfunction DC statin Renal Effects Miniscule and transient Cognitive Effects Did not lead to significant cognitive decline New onset DM Seen only in older patients Risks do not outweigh benefits McKenney et al Am J Cardiol. 2006; 97 (suppl 8A): 88C-94C. What else can be done??? Red Yeast Rice 4

5 Sedentary Lifestyle? GET SWEATY!!! Dietary changes Niacin Soluble fiber/ Portfolio diet % LDL reduction Sterols/stanols- 5-10% LDL reduction Lipid Changes LDL-C 5-25% HDL-C 15-35% Trig 20-50% Versions Immediate Release Slow Release Extended Release Jacobson TA Mayo Clin Proc 83 (6): Hyperglycemia Bile Acid Resins Lipid Changes Side Effects Hepatotoxicity Flushing LDL-C 15-30% HDL-C 3-5% Trig 0- increase GI complaints Medication interactions Hyperuricemia WHY ARE THEY SO BIG? 5

6 NO, NO, NO! Cholesterol Absorption Inhibitor Lipid Changes LDL-C 18% HDL-C 1% Trig 7% Safe Well tolerated Usually add on CLINICAL TRIALS? 6