Lipid Assessment and Management: Analzye and Apply Current Guidelines from the USPS Task Force and ACCF/AHA Sally K. Miller, PhD, APN, FNP-BC, FAANP Associate Professor University of Nevada Las Vegas School of Nursing Nurse Practitioner Correct Care Solutions iCarePsychiatry Las Vegas, NV 1 Disclosures • I have no financial affiliations to disclose Objectives • At the conclusion of this program the attendee will: –Differentiate lipid management from cardiovascular risk reduction 3 Objectives –Analyze current guidelines for primary and secondary cardiovascular risk reduction –Analyze the mechanism of action of drugs for ASCVD risk reduction and lipid lowering –Apply pharmacotherpeutic principles in case studies 4 2013 ACC/AHA Guidelines on the Treatment of Blood Cholesterol 5 What’s Different? • No clear value to adding additional drug classes for LDL reduction • LDL reduction is either “high intensity” or “moderate intensity” – no goal numbers 6 What’s Different? • Generally speaking, the other classes of lipid-lowering agents do not offer a benefit worth the cost, risk of adverse effects, and risk of statin-related interaction 7 No Role in ASCVD Risk Reduction • Niacin • Bile acid sequestrants • Fibric acid derivatives • Fish oil ** Some of these medications may have a role in other lipid disorders, e.g., hypertriglyceridemia 8 Statins are Categorized According to % LDL reduction • High intensity – > 50% reduction –Atorvastatin 40-80 mg daily –Rosuvastatin 20-40 mg daily 9 • Medium intensity – 30-49% reduction –Atorvastatin 10-20 mg daily –Rosuvastatin 10-20 mg daily –Simvastatin 20-40 mg daily –Pravastatin 40-80 mg daily –Lovastatin 40 mg daily 10 • No role for low intensity -- < 30% reduction –Pravastatin 10-20 mg daily –Lovastatin 20 mg daily 11 Four Statin Treatment Groups • Candidates for statin therapy are divided among four treatment groups 12 Statin Treatment Group #1 • Anyone over 21 – 75 years old with ASCVD –High intensity statin • Anyone > 75 year old or not a candidate for high intensity statin –Moderate intensity statin 13 Statin Treatment Group #2 • Any patient who has an LDL of > 190 mg/dL –No caveats according to age 14 Statin Treatment Group #3 • Patients between the ages of 40 – 75 years with type 1 or 2 diabetes mellitus –Moderate intensity therapy • This patient group with a 10 year ASCVD risk > 7.5% –High intensity statin 15 Statin Treatment Group #4 • Anyone 40-75 years old with a 10-year pooled risk for ASCVD > 7.5% –Moderate to high intensity statin therapy 16 Calculating Pooled Risk 17 USPS Task Force Recommendations Statin Use for Primary Prevention • Adults 40-75 years with no hx of CVD, 1 or more risk actors, and a 10 year risk > 10% –Low to moderate intensity statin –Level B recommendation 18 USPS Task Force Recommendations Statin Use for Primary Prevention • Adults 40-75 years with no hx of CVD, 1 or more risk actors, and a 10 year risk 7.5 to 10% –Consider low to moderate intensity statin –Benefit not as clear due to lower probability of disease –Level C recommendation 19 USPS Task Force Recommendations Statin Use for Primary Prevention • Insufficient evidence to assess the benefits and harms of initiating statins for primary prevention in patients 76 years of age and older without a hx of CVD 20 Case Study W.R. • W.R. is a 46-year-old Black male who presents for his annual wellness exam. • He denies any complaints – he is taking HCTZ for a diagnosis of HTN and feels well 21 W.R. • W.R.’s ROS is negative; he offers no complaints at all and is only here because he needs refills on his HCTZ 22 W.R. • Vital signs as follows: –Ht 70” Wt 235 lbs –98.5o F, 86 b.p.m., RR 18, 130/84 mm Hg • Physical exam is unremarkable 23 W.R. • Fractionated lipid profile as follows: –TC 266 mg/dL –HDL 67 mg/dL –LDL 168 mg/dL –TG 235 mg/dL 24 W.R. • Does W.R. need statin therapy? –Does he have existing ASCVD? –Does he have an LDL > 190 mg/dL? –Does he have type 1 or 2 DM? –Is his ASCVD 10 year risk > 7.5%? 25 W.R. 10 Year ASCVD Risk •Gender: Male • Age: 46 years old • Race: Black • TC: 266 mg/dL • HDL: 67 mg/dL • Sys BP: 130 mm Hg •Txfor HTN? Yes •DM? No •Smoker? No 26 K.G. • K.G. is a 42 year-old female who presents for an occupational biometrics examination • She denies any significant medical history and takes no daily medications 27 K.G. • K.G. denies any surgical history • K.G.’s social history includes –Married for 16 years, no children –1-2 drinks socially per month –1 pack of cigarettes daily for 20 years 28 K.G. • K.G.’s ROS is significant for: –Irregular menses –Occasional fatigue –Bilateral knee pain – Thinning hair 29 K.G. • Vital signs are as follows: –Ht 65” Wt 125 lbs –97.4o F, 62 b.p.m., RR 14, 134/78 mm Hg • Physical exam is unremarkable 30 K.G. • Fractionated lipid profile as follows: –TC 239 mg/dL –HDL 40 mg/dL –LDL 149 mg/dL –TG 201 mg/dL 31 K.G. • Does K.G. need statin therapy? –Does she have existing ASCVD? –Does she have an LDL > 190 mg/dL? –Does she have type 1 or 2 DM? –Is her ASCVD 10 year risk > 7.5%? 32 W.R. 10 Year ASCVD Risk •Gender: Female • Age: 42 years old • Race: Non-black • TC: 239 mg/dL • HDL: 40 mg/dL • Sys BP: 134 mm Hg •Txfor HTN? No •DM? No •Smoker? Yes 33 Benefits of Statins Beyond LDL Reduction • Pleotropic effects are uncertain at best –Improved endothelial cell function –Halting atheroma development –Reduced inflammation –Antithrombotic effects 34 The Very High Risk Patient • Guidelines are used to frame assessment and management decision in the majority of patients • There remain a group of very high risk patients who fall outside of standard guidelines 35 PCSK9 Inhibitors • The newest class of lipid lowering agent • Indicated for patients with – Heterozygous or homozygous familial hyperlipidemia who are tolerating maximal statin doses – Clinical ASCVD who need additional LDL lowering after maximal statin therapy PCSK9 Inhibitors • Under normal circumstances hepatic LDL receptors bind LDL and remove it from circulation – When the receptor returns to function, naturally occurring PCSK9 binds (blocks) it and interferes with further LDL receptor functioning – Because PCSK9 and LDL are dynamic physiologic processes, statins can actually increase PCSK9 activity PCSK9 Inhibitors • These medications block the naturally occurring protein PCSK9 that binds to LDL receptors on hepatocytes • By using this class of medication to block this protein, we block the degradation of LDL receptors • LDL receptors stay expressed on hepatocytes, and continue to facilitate removal of LDL from circulation PCSK9 Inhibitors • Generally LDL reduction is appreciated in the 50% range • This class of medication is currently not indicated for those who are intolerant of statins • At this point there are no data to support reduced cardiovascular events PCSK9 inhibitors • Very expensive – between $13,000 and $14,000 annually • Currently two are approved –Alirocumab (Praluent) –Evolocumab (Repatha) • Bococizumab is in phase III trials PCSK9 Inhibitors • Serious adverse events have not been a big issue – There have been hypersensitivity reactions – Most common adverse events – URI type symptoms –Back pain – Injection site reactions Remember… • Most FNPs will not be managing lipid abnormalities – you will be managing ASCVD risk with statins • Non-statin lipid medications are used for patients with familial or other mixed lipid abnormalities • At this point, patients requiring PCSK9 inhibitor will likely have this initiated by cardiology Other Medications Not Used for ASCVD Risk Reduction May be used in the management of other forms of dyslipidemia 43 Bile Acid Sequestrants – Cholestyramine, Colestipol, WelChol • Mechanism of action –Binds bile acids in the gut, interrupting reabsorption –More bile acids must be synthesized in the liver –LDL receptors on hepatocytes are increased 44 Bile Acid Sequestrants – Cholestyramine, Colestipol, Welchol •Dosing –WelChol in 625 mg tabs –Should be taken before meals 45 Bile Acid Sequestrants – Cholestyramine, Colestipol, Welchol • Side effects –Constipation –GI irritation or bleeding –LFT abnormalities –Complete bile duct obstruction –Hypertriglyceridemia 46 Bile Acid Sequestrants – Cholestyramine, Colestipol, Welchol • Side effects (cont.) –Drug interactions •Interferes with absorption of fat soluble vitamins •Interferes with absorption of oral anticoagulants, digoxin, penicillins, thyroid hormone, tetracyclines, iron salts 47 Fibric Acid Derivatives • Mechanism of action – Gemfibrozil (Lopid), fenofibrate (Tricor) and fenofibric acid (Trilipix)* – Increase activity of lipoprotein lipase, promoting catabolism of VLDL and triacylglycerols – Blocks lipolysis of triacylglycerols stored in adipose tissue – Not routinely indicated for coadministration with statins; if truly necessary, only Trilipix is indicated 48 Fibric Acid Derivatives • Mechanism of action –Stimulate endothelial receptor production of LPL –Significant reduction of triacylglycerol 49 Fibric Acid Derivatives • Adverse effects –Cholelithiasis –Dyspepsia, diarrhea –Myositis –LFT abnormalities –Headache, dizziness –Impotence 50 Fibric Acid Derivatives • Laboratory evaluation –Liver and renal function tests at start of therapy –May decrease serum glucose –May decrease serum uric acid 51 Cholesterol Absorption Inhibitor • Only one in class - ezetimibe • Mechanism of action –Complexes with bile salts and blocks absorption of cholesterol from very precise absorption sites in the duodenum 52 Cholesterol Absorption Inhibitor • Mechanism of action – Decreased absorption from the gut leads to decreased cholesterol stores in the hepatic free cholesterol pool – Resulting upregulation of LDL-C receptors increases plasma clearance of LDL by up to an additional 25% 53 Cholesterol Absorption Inhibitor • When given with an HMG-CoA reductase inhibitor –May increase risk of myositis and other statin-related effects –Should not be given in moderate to severe hepatic insufficiency 54 References • American College of Cardiology/American Heart Association Task Force. (2014).