Dall slides for Heart org Review 53 yr

Dall slides for Heart. org Review

53 yr old Male HTN, dyslipidemia, RA � 53 y/o male with hx low HDL and high triglycerides and history of elevated LFTS, prior statin intolerance not on any lipid therapy � PMH: HTN, rheumatoid arthritis, Impaired fasting glucose � Medications: Aspirin 81, Entanercept, Diliazem, Hydrochlorothiazide � No lipid meds due to statin intolerance (simvastatin and atorvastatin) which caused myalgias, elevated liver enzymes � Family history: Father died age 51 MI

Physical Exam �Wt 235 lbs �Ht 71 in �WC 45 in �BMI 32 �No evidence of tendinous xanthomas or corneal arcus

Initial Labs LIPIDS/LIPOPROTEINS � � � � T Cholesterol 210 mg/d. L TG 183 mg/d. L HDL-C 37 mg/d. L LDL-C 143 mg/d. L non-HDL-C 173 mg/d. L LDL-P 3021 nmol/L small LDL-P 2813 nmol/L Apo B 124 OTHER MARKERS � � � � 25 OH Vitamin D 27 ng/L Creatinine 1. 1 Fasting Glucose 106 Hg. AIC 5. 9 CK normal ALT 84 (ULN 56 U/L) AST 36 (normal range) TSH 1. 59 (normal) All lipid and lipoprotein measurements in abnormal range

Issues to Address � Previous myalgias on simvastatin and atorvastatin? • Drug alternatives? • Elevated LFTs? Does this impact treatment options? � Any additional therapies • Vitamin D • Coenzyme Q 10 � Address secondary causes • Diet • Impaired glucose dyslipidemia

Approximate Dose-Equivalency of Statin LDL-C Efficacy -----------dose of agent (mg/d)----------Rosuv Atorva Simva Pitava Lova Prava Fluva Approx a* * ↓LDL-C 10 1 20 40** 80 5 10** 2** 40** 10** 20 40 4 80 *Atorva be more effective (½ and 1 doubling 20 and rosuva 40 may(80) **Most commonly used dose in US. Adapted from: Roberts WC. Am J Cardiol. 1997; 80: 106 -107. Stein E et al. J Cardiovasc Pharmacol Therapeut. 1997; 2: 7 -16. Rosuvastatin PI, Pitavastatin PI. 40 80 40 2834% 80** 3542% 3947% respectively). 4652% 51 -

Statin Metabolism: Many Similarities, Some Key Differences Factor Pitava Rosuv Atorv Simv a a a Lov Prava Fluv a a Absorp (%) 80 50 30 60 -85 30 35 98 Bioav (%) 60 20 12 <5 5 18 30 T ½ (h) 10 -13 20 7 -20 2 -5 1 -3 CYP +/- 3 A 4 - 2 C 9 OATP 1 B 1 + + + + “+/-” = minimal metabolism by by pathway MDR 1 + - pathway. “-” + = no metabolism + + + ? Adapted from : Neuvonen, PJ et al, Clin. Pharm & Ther. 2006; 80: 565 -81

Metabolism of Statins by the Cytochrome P 450 System CYP 3 A 4 Atorvastatin CYP 2 C 9 Fluvastatin CYP 3 A 4 Lovastatin CYP 2 C 9 minimal CYP 2 C 9 CYP 3 A 4 Saito Y. Vasc Health Risk Manag. 2009; 5: 921 -936. Pitavastatin Pravastatin minimal Rosuvastatin Simvastatin

Statins and CYP 3 A 4 Inhibition Rhabdomyolysis cases per 10 million prescriptions Pravastatin (25 cases) Simvastatin (118 cases) With CYP 3 A 4 inhibitor 2. 4 38. 4 Without CYP 3 A 4 inhibitor 3. 1 6. 0 Rowan C et al. Pharmacoepidemiol Drug Saf 2009; 18: 301– 309.

Simvastatin Label Change 6/8/11: New Maximum Doses by Interacting Drugs Interacting Drug Class Anti-arrhythmic Agent Amiodarone Verapamil Antihypertensive Diltiazem Amlodipine Anti-anginal Ranolazine Label Old 20 mg max “ 40 mg max 80 mg max “ Merck Healthcare Provider letter June 8, 2011 http: //www. simvastatininfocenter. com/documents/hcpletter. pdf New 10 mg max “ “ 20 mg max “

Metabolic Pathways of Statins Less Prone to DDI �Fluvastatin: mainly CYP 2 C 9 (less common CYP) +/- via 3 A 4 & 2 D 6 �Rosuvastatin little CYP, +/- via 2 C 9 & 2 C 19 �Pitavastatin little CYP, +/- via 2 C 8 & 2 C 9 �Pravastatin avoids CYP 450 system altogether These four statins are recommended most often for DDI issues, see Pharmacist’s Ltr/Prescriber’s Ltr. Aug 2009; 250812. All statins have potential DDI via glucuronidation (fluvastatin less commonly).

Statin Use in Complex Patients: Program Summary � As of 2011, we have many excellent statin choices: • Very high-efficacy (high-dose rosuva & atorva + fixed-dose combos) • High safety/tolerability* (prava & fluva) • Mixed safety/efficacy* (low-dose rosuva, high-dose pitava) • Variety of inexpensive generics (pravastatin, lovastatin, simvastatin, atorvastatin newly generic end-2011) *Especially useful in complicated and challenging patients

Follow up visit 3 months Initial visit Intolerant to statins, elevated LFTs 3 month follow up rosuvastatin 10, Metformin 2000, Vit D 3 4000 IU Total Cholesterol 210 112 Triglyceride 183 74 HDL-C 37 26 LDL-C 143 68 LDL-P Small LDL P 3021 2813 1461 1339 Non HDL-C 173 86 Vitamin D 27 64 ALT Hb. A 1 c Weight 84 5. 9 235 56 5. 5 217