Lipid Treatment Updates in Management Debra Griner, MS FNP-C Mesa Primary Care Casper, Wyoming

Disclosures None

Objectives Identify causes of hyperlipidemia (HLD) Treatment Guidelines Who should be treated for HLD & Goal 3. Prevention

Causes of Hyperlipidemia Genetic Predisposition (Primary HLD) Poor Diet: saturated fat (animal fat), trans fat(cake/cookies), high cholesterol (red meat, full fat dairy products) Obesity BMI 30 or more: waist circumference men >= 40 inches & women >= 35 inches Lack Exercise/Sedentary Lifestyle: exercise boosts HDL and increases size of particles that make up LDL making it less harmful Smoking: damages walls of blood vessels and lowers HDL levels DM: High BS contributes to ↑ LDL & ↓ HDL and damages lining of arteries

Every time you eat or drink, you are either fighting disease……... or feeding it.

Treatment Guidelines 2013 ACC/AHA Cholesterol Guidelines are fairly limited in scope and did not address all clinical scenarios such what to do with HDL-C, non-HDL-C, apolipoprotein B (apoB), and triglycerides. ATP IV Guidelines expected out later 2018 LDL-C continues to be target in treatment because it is the most atherogenic lipoprotein Statin therapy will likely continue to be emphasized as they are most effective lipid lowering agents for reducing LDL-C Treating to new Targets Trial demonstrated lower incidence of major CV events in the intensive statin therapy group

The 2016 European Society of Cardiology/European Atherosclerotic Society (ESC/EAS) guidelines and the 2017 American Association of Clinical Endocrinologists and American College of Endocrinology (AACE) guidelines provide more current recommendations for lipid management.  The IMPROVE-IT (Examining Outcomes in Subjects With Acute Coronary Syndrome: Vytorin vs Simvastatin) and FOURIER (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) trials found that lower is better when it comes to LDL-C and non-HDL-C and extremely low LDL-C (<20 mg/dL) has been shown to be safe in short term follow-up and possibly beneficial.

Based upon these more recent trials, both the AACE and the ESC/EAS have recommended specific LDL-C targets for specific risk categories. This shift towards specific LDL-C goals is also supported by the recently published 2016 ACC expert consensus decision pathway on the role of non-statin therapies which also provides optional target LDL-C goals, making this recommendation even more significant.

2016 ACC Expert Consensus Decision Pathway on Role Non-statin Therapy for LDL-C lowering in the Management of ASCVD Patient Populations Addressed: Four Statin Benefit Groups Sub- Populations of these Groups Special Populations

FOUR STATIN BENEFIT GROUPS Adults > 21 years with clinical ASCVD on statin for secondary prevention. Adults > 21 years with LDL-C > 190mg/dL Not due to secondary modifiable causes on statin for primary prevention. Adults 40-75 years without ASCVD BUT with DM & LDL-C 70-189mg/dL on statin for primary prevention. Adults 40-75 years without ASCVD or DM with LDL-C 70-189 mg/dL & an estimated 10 year risk ASCVD of >7.5% on statin for primary prevention. Note: Few people 75 years or older were enrolled in RCT (randomized controlled trial) but available evidence DOES support continuation of moderate intensity statin therapy beyond 75 years of age in those already taking and tolerating statins and for secondary prevention in individual with clinical ASCVD.

Patient with Stable Clinical ASCVD without Comorbidities Treat with maximally tolerated statin Achieve at least > 50% LDL-C reduction If reduction not achieved, consider non-statins: LDL-C treatment threshold > 100mg/dL Try Zetia (ezetimibe) first & consider BAS if TG<300mg/dL PCSK9 inhibitor next If treatment objective achieved, follow lipids If not, reassess medication adherence and lifestyle

Clinical ASCVD with Co-Morbidities: DM, Recent acute ASCVD event, ASCVD event on statin, Baseline LDL-C > 190mg/dL, Uncontrolled risk factors, Elevated Lp(a), CKD Treat with maximal tolerated statin Achieve at least >50% LDL-C reduction If this reduction is not achieved, initiate discussion & consider non- statins if LDL-C >70mg/dL, or non-HDL-C>100mg/dL if Diabetic Zetia First PCSK-9 inhibitor next If treatment obj met follow lipids, if not reassess medication adherence and lifestyle Consider Mipomersen, lomitapide &/or LDL apheresis in appropriate pts

Patient without Clinical ASCVD & Baseline LDL-C > 190mg/dL Treat Maximally tolerated statin Strong recommendation to lipid specialist Achieve at least >50% LDL-C reduction If reduction not achieved, initiate discussion with pt & consider non-statins if LDL-C> 100mg/dL Try Zetia first; consider BAS if TG<300mg/dL PCSK9 Inhibitor next If treatment objectives achieved, follow lipids Consider Mipomersen, lomitapide &/or LDL apheresis in appropriate pts

Patients 40-75 yo without Clinical ASCVD & DM (10 yr ASCVD risk <7 Treat with moderate or high intensity statin Achieve %LDL-C or non-HDL-C reduction then follow serial lipids If expected % reduction not achieved or if LDL-C >100mg/dL or non-HDL-C >130mg/dL, if at moderate intensity consider increase to high intensity statin & monitor adherence Additional therapy not recommended

Patients 40-75yo without Clinical ASCVD & DM (10yr ASCVD risk > 7 Start with moderate or high intensity statin Increase to high intensity statin if need to achieve expected LDL-C or non-HDL-C % reduction May consider non-statins for LDL-C >100mg/dL or non-HDL-C >130mg/dL Zetia or BAS (if TG<300mg/dL) PCSK9 Inhibitors not currently indicated Monitor adherence

Patients 40-75 yo without Clinical ASCVD & with 10 year ASCVD risk >7.5% Consider high-risk markers After discussion with pt start moderate or high intensity statin Assess for %LDL-C reduction achieved If % reduction inadequate, increase to high intensity statin If achieve expected % LDL-C reduction, monitor May consider non-statins for LDL-C >100mg/dL -Zetia or BAS (if TG<300mg/dL) in higher risk pts -PCSK9 Inhibitors not indicated

Patients 40-75 yo without Clinical ASCVD & with 10 yr ASCVD Risk > 7.5% HIGH RISK MARKERS -Pooled cohort Equation 10 yr risk >20% -LDL-C >160mg/dL -Uncontrolled major ASCVD risk factors -Family history of premature ASCVD -Elevated Lp(a) -Accelerated subclinical ASCVD -CKD -HIV or other inflammatory Disorders

SPECIAL POPULATIONS Heart Failure NYH Class II-III: follow algorithm for ASCVD with comorbidities & consider expected longevity Hemodialysis Patients: Individualize care Women Childbearing age considering pregnancy -Statins should be used for premenopausal women generally ONLY IF ASCVD, FH, or high risk, & on contraception. -D/C Lipid lowering drugs immediately if pregnant; >1 & preferably 3 months prior to attempting conception -Lifestyle & monitor LDL-C during pregnancy -Consider referral to lipid specialist for FH -May consider BAS (monitor for Vitamin K deficiency) -May resume statin/Zetia after completion of breast feeding

FACTORS TO CONSIDER Adherence & Lifestyle –HH diet, Regular exercise, No tobacco, healthy weight Evaluate for Statin Intolerance Control of other risk factors Clinician-patient discussion regarding potential benefits, potential harms, & patient preferences regarding addition of non statin medications Percentage LDL-C Reduction ( may consider absolute LDL-C level achieved) Monitoring Response to therapy, adherence, & lifestyle

Optional Interventions to Consider Refer to Lipid Specialist & registered dietician Ezetimibe Bile Acid Sequestrants PCSK 9 Inhibitors - Praluent (Alirocumab), Repatha (evolocomab) Mipomersen, Lomitapide, LDL aphresis may be considered by a lipid specialist Niacin is NOT routinely recommended

Addressing Statin Intolerance ACC Statin Intolerance App -http://www.acc.org/StatinIntoleranceApp Careful history of myalgia patterns Consideration of secondary causes Wash-out and rechallenge -consider changing drug, dose, alternative dosing

HIGH INTENSITY STATIN THERAPY Lowers LDL-C on average by approximately >50% LIPITOR 40MG-80MG DAILY CRESTOR 20MG-40MG DAILY Statins that are bold evaluated in RCT

MODERATE INTENSITY STATIN Daily dose lowers LDL-C by approximately 30-50% Lipitor 10mg-30mg Fluvastatin 40mg BID Crestor 5mg-10mg Pitavastatin 2mg-4mg Simvastatin 20mg-40mg Lovastatin 40mg Pravastatin 40mg-80mg Statins that are bold evaluated in RCT

LOW INTENSITY STATINS Lowers LDL-C on average 21-29% Fluvastatin 20mg-40mg Pravastatin 10mg-20mg Simvastatin 10mg Lovastatin 20mg Pitavastatin 1mg Statins that are bold evaluated in RCT

The Consensus Group endorsed the use of fasting lipid panel and Friedewald calculation of LDL-C as per 2013 Guidelines -Citing both were used in almost all RCT -Widely available lower cost -Acknowledge limitations in accuracy at lower LDL-C levels

57 yo woman comes to see you for cholesterol 57 yo woman comes to see you for cholesterol. She is active though no regular exercise. 1ppd smoker and father died age 58 from AMI. She has not been to a doctor in 20 years. Her only medication is ASA 325mg/d BP 148/86 Fasting Blood sugar 98 Lipids: Total Chol 144 TG 85 HDL 44 LDL 83. Regarding cholesterol what is the next best step at this point? Start on generic atorvastatin 20mg/d Calculate risk for CV event Suggest she see a dietician Perform an exercise stress test Suggest she quit smoking?

Clinicalc.com- Pooled Cohort Risk Assessment Equation Risk Factors for ASCVD Gender Male Female SBP 148 mmHg Age 57 years Receiving treatment No Yes for HTN (If SBP >120) Race White or other Diabetes No Yes Total Cholesterol 144 mg/dL Smoker No Yes HDL Cholesterol 44 mg/dL

Optimal Risk Factors Include: ASCVD Risk Evaluation 10 year risk of Atherosclerotic cardiovascular disease 6.5% 10 year risk in similar patient with optimal risk factors 1.7% Lifetime risk of Atherosclerotic cardiovascular disease 39% Lifetime risk for 50 year old with optimal risk factors 8% Optimal Risk Factors Include: Total Cholesterol of < 170mg/dL HDL Cholesterol of 50mg/dL SBP of 110mmHg Not taking medications for Hypertension Not a diabetic Not a Smoker

Screen for CV Risk Factors & Measure LDL > 21 yo Practical Approach to the New Cholesterol Guidelines Screen for CV Risk Factors & Measure LDL > 21 yo AtheroCVD DM 1 or 2 Age 40-75 LDL 70-189 No DM Age 40-75 LDL 70-189 LDL> 190mg High Dose Statin 10 year Risk 10 year Risk High Dose Statin < 7.5%, Mod Dose > 7.5% High Dose > 7.5% Mod-Hi Dose

The food you eat can be either the safest & most powerful form of Medicine or the slowest form of poison.