Managing Lipids and Cardiovascular Risk: Using the Data to Optimize Care

Transcription

1 Clinical Updates for Nurse Practitioners and Physician Assistants: 2018 Managing Lipids and Cardiovascular Risk: Using the Data to Optimize Care Faculty Robert L. Gillespie, MD, FACC, FASE, FASNC Immediate Past Chairman of the Board Association of Black Cardiologists, Inc. Director of Nuclear Imaging Sharp Rees-Stealy Medical Group San Diego, CA Alanna A. Morris, MD, MSc, FHFSA Assistant Professor of Medicine Division of Cardiology Emory University School of Medicine Atlanta, GA 2 Faculty Robert L. Gillespie, MD, FACC, FASE, FASNC Immediate Past Chairman of the Board, Association of Black Cardiologists Director of Nuclear Imaging, Sharp Rees-Stealy Medical Group San Diego, CA David Montgomery, MD, PhD, FACC Preventive Cardiologist Piedmont Heart Institute Atlanta, GA Karol E. Watson, MD, PhD Professor of Medicine/Cardiology Co-director, UCLA Program in Preventive Cardiology Director, UCLA Barbra Streisand Women s Heart Health Program Los Angeles, CA 3 1

2 Disclosures Dr. Gillespie serves as a Consultant and Speaker for Boston Scientific. Dr. Morris has no financial relationships to disclose. 4 Learning Objectives 1. Describe the findings from recent trials of PCSK9i hypercholesterolemia treatments on cardiovascular outcomes. 2. Discuss current guidelines and recommendations for the management of hyperlipidemia in high risk patients. 3. Incorporate current data into secondary prevention treatment strategies for patients with the highest cardiovascular risk. 4. Recognize barriers to access for PCSK9 monoclonal antibody therapy and discuss strategies to overcome them. 5 PRE-TEST QUESTIONS 6 2

3 Pre-test ARS Question 1 How confident are you in your ability to determine which patients may benefit from use of a PCSK9 inhibitor? 1. Not at all confident 2. Slightly confident 3. Moderately confident 4. Pretty much confident 5. Very confident 7 Pre-test ARS Question 2 How often do you consider non-statin therapies for patients with high ASCVD risk and LDL-C not at recommended target, despite use of maximally tolerated statin? 1. Never 2. Rarely 3. Sometimes 4. Frequently 5. Always 8 Pre-test ARS Question 3 Approximately how many patients with hyperlipidemia do you see on a weekly basis, in any clinical setting? 1. None >

4 Statin Effects on Vascular Events Endpoint Events (%) Treatment Control Rate Ratio (CI) Non-fatal MI 2001 (4 4) 2769 (6 2) 0 74 ( ) CHD death 1548 (3 4) 1960 (4 4) 0 81 ( ) Any major coronary event 3337 (7 4) 4420 (9 8) 0 77 ( ) CABG 713 (3 3) 1006 (4 7) 0 75 ( ) PTCA 510 (2 4) 658 (3 1) 0 79 ( ) Unspecified 1397 (3 1) 1770 (3 9) 0 76 ( ) Any coronary revascularisation 2620 (5 8) 3434 (7 6) 0 76 ( ) Haemorrhagic stroke 105 (0 2) 99 (0 2) 1 05 ( ) Presumed ischaemic stroke 1235 (2 8) 1518 (3 4) 0 81 ( ) Any stroke 1340 (3 0) 1617 (3 7) 0 83 ( ) Any major vascular event 6354 (14 1) 7994 (17 8) 0 79 ( ) CTT. Lancet : Favors statin 10 Reduction in Stroke Risk With Statin Therapy Risk Reduction CARE (N = 4159) Prava 40mg -32% P = 0.03 LIPID (N = 9014) Prava 40mg -19% P = MIRACL (N = 3086) Atorva 40mg Meta-analysis (N = 21,303) Lova Prava Simva -31% P = 0.03 HPS (N = 20,536) Simva 40mg -27% 2P < % P = Plehn JF, et al. Circulation. 1999;99: ; The LIPID Study Group. N Engl J Med. 1998;339: ; Schwartz GG, et al. JAMA. 2001;285: ; Ross SD, et al. Arch Int Med. 1999;159: ; Fox R. Circulation. 2001;104:e9051. Prava = Pravastatin Atorva = Atorvastatin Simva = Simvastatin Lova = Lovastatin 11 An underappreciated benefit of statin therapy is stroke reduction 12 4

5 2013 ACC-AHA Cholesterol Guidelines Stone NJ et al. Circulation. 2014;129:S Pre-test ARS Question 4 70-year-old woman, 15-year history of hypertension, 10- year history of dyslipidemia NSTEMI 1 year ago, LDL-C is 88 mg/dl Current medications include lisinopril/hydrochlorothiazide 40/25 mg qd, metoprolol tartrate 100 mg bid, rosuvastatin 40 mg qd, and aspirin 81 mg qd After reviewing the brief scenario above, please rate this statement as consistent with or not consistent with best clinical practice: Switch to atorvastatin 80 mg: 1. Yes, it is consistent 2. No, it is not consistent 14 ACC/AHA Statin Benefit Groups Secondary Prevention Clinical ASCVD Primary Prevention LDL-C > 190 mg/dl Diabetes Mellitus Primary Prevention > 7.5% 10-yr ASCVD risk Age < 75: High-intensity statin Age > 75: Moderate-intensity statin High-intensity statin 10-yr risk < 7.5%: Moderate-intensity statin 10-yr risk > 7.5%: High-intensity statin Consider moderate or high intensity statin Stone NJ et al. Circulation. 2014;129:S

6 High Intensity Statin Daily dose lowers LDL-C ~50% Intensity of Statin Therapy Moderate Intensity Statin Daily dose lowers LDL-C 30% -50% Low Intensity Statin Daily dose lowers LDL-C <30% Atorvastatin (40 )-80 mg Rosuvastatin 20 (40) mg Atorvastatin 10 (20) mg Rosuvastatin (5) 10 mg Simvastatin mg Pravastatin 40 (80) mg Lovastatin 40 mg Fluvastatin XL 80 mg Fluvastatin 40 mg bid Pitavastatin 2-4 mg Simvastatin 10 mg Pravastatin mg Lovastatin 20 mg Fluvastatin mg Pitavastatin 1 mg Stone NJ et al. Circulation. 2014;129:S The intensity of lipid-lowering therapy should match the intensity of risk 17 Inter-patient Variability in Response to Statins The graph below shows dramatic inter-individual variability in response to a statin (Atorvastatin 10 mg daily) Pedro-Botet J et al. Atherosclerosis 158 (2001)

7 Even though statins are robust LDL lowering drugs, there is significant inter-patient variability in statin response 19 LDL-C (mg/dl) Rationale for Pushing LDL-C Levels Even Lower Meta-analysis of 38,153 patients from 8 randomized statin trials < < < < <75 LDL-C Levels and Risk of CV Events < Adjusted Hazard Ratio 95% CI Boekholdt SM, et al. JACC. 2014;64(5): Event Rate (%) Major CV and Coronary Event Rates 50 vs Various LDL-C Levels <50 Major Coronary Events Major CV Events LDL-C (mg/dl) 34.4 > Non-statin Therapies The 2013 ACC-AHA cholesterol guidelines were intentionally vague on the use of non-statin therapy in addition to statins To offer clinicians more guidance, the American College of Cardiology convened Expert Consensus Decision Pathway committees to answer the questions In what patient populations should nonstatin therapies be considered? Which agents or therapies should be considered? Lloyd-Jones D et. al. J Am Coll Cardiol. 2016;67(5):

8 Pre-test ARS Question 5 70-year-old woman, 15-year history of hypertension, 10- year history of dyslipidemia NSTEMI 1 year ago, LDL-C is 88 mg/dl Current medications include lisinopril/hydrochlorothiazide 40/25 mg qd, metoprolol tartrate 100 mg bid, rosuvastatin 40 mg qd, and aspirin 81 mg qd After reviewing the brief scenario above, please rate this statement as consistent with or not consistent with best clinical practice: Add ezetemibe: 1. Yes, it is consistent 2. No, it is not consistent 22 Pre-test ARS Question 6 70-year-old woman, 15-year history of hypertension, 10-year history of dyslipidemia NSTEMI 1 year ago, LDL-C is 88 mg/dl Current medications include lisinopril/hydrochlorothiazide 40/25 mg qd, metoprolol tartrate 100 mg bid, rosuvastatin 40 mg qd, and aspirin 81 mg qd Ezetimibe is added. Six months later, LDL-C is 72 mg/dl. After reviewing the brief scenario above, please this statement as consistent with or not consistent with best clinical practice: Add PCSK9 inhibitor: 1. Yes, it is consistent 2. No, it is not consistent 23 Guidance on Use of Nonstatin Therapy All patients with ASCVD on statin Primary: >50% reduction in LDL-C Secondary (may consider): LDL-C <70 mg/dl Non-HDL-C <100 mg/dl Lloyd-Jones DM, et al. JACC. 2017;70(14): Ezetimibe or a PCSK9 inhibitor are the only non-statins recommended 24 8

9 IMPROVE-IT Trial 18,144 patients with recent ACS simvastatin 40 mg vs. simvastatin 40 mg + ezetimibe 10 mg Event rate % Simvastatin alone (median LDL 69 mg/dl) Simvastatin + ezetimibe (median LDL 54 mg/dl) RRR = 6% NNT = 50 Christopher Cannon et. al. N Engl J Med 2015; 372: Questions to Consider 26 PCSK9 (Proprotein convertase subtilisin/kexin type 9) A secreted protein which targets the LDL receptor for degradation Gain of function mutations cause high LDL-C Loss of function mutations cause low LDL-C Inhibition lowers LDL-C levels Up-regulated by statin therapy 27 9

10 How is cholesterol removed from blood? LIVER Circulating LDL particles (which contain a large ApoB protein) are grabbed by an LDL receptor 28 How is cholesterol removed from blood? LIVER The entire complex is then internalized into the hepatocyte for LDL destruction 29 How is cholesterol removed from blood? Then the LDL particle is destroyed LIVER As the LDL particle is being destroyed, the LDL receptor migrates back to the hepatocyte cell surface so that it can grab more LDL molecules 30 10

11 How is cholesterol removed from blood? LIVER When PCSK9 is present, however, the LDL receptor gets stuck before it adheres to LDL and cannot migrate back to the surface It therefore gets destroyed along with the LDL And surface LDL receptors are depleted from the cell surface causing a rise in plasma levels of LDL particles and LDL-C 31 The theory behind PCSK9 inhibitors LIVER X If PCSK9 is inhibited, the LDL receptor can migrate back to the cell surface And surface LDL receptors will be restored so they can degrade LDL particles and lower serum cholesterol 32 Pre-test ARS Question 7 In the FOURIER trial, what was the numberneeded-to-treat to prevent an instance of the primary outcome (major cardiovascular events) with evolocumab compared to placebo?

12 Fourier Trial Design - Evolocumab 27,564 high-risk, stable patients with established CV disease (prior MI, prior stroke, or symptomatic PAD) Screening, Lipid Stabilization, and Placebo Run-in High or moderate intensity statin therapy (± ezetimibe) LDL-C 70 mg/dl or non-hdl-c 100 mg/dl Evolocumab SC 140 mg Q2W or 420 mg QM RANDOMIZED DOUBLE BLIND Placebo SC Q2W or QM Sabatine MS et al. Am H J 2016; 173: Follow-up ~ 3 years 34 Fourier Trial Lipid Results Placebo LDL Cholesterol (mg/dl) % mean reduction, P< Absolute reduction: 56 mg/dl (95%CI 55-57) (median LDL on Evolocumab 30 mg/dl, IQR mg/dl) Weeks Sabatine MS et al. Am H J 2016; 173: Fourier Trial: Primary Outcome 16% 14% 12% 10% 8% 6% 4% 2% 0% Placebo Evolocumab 15% RRR NNT = Months Sabatine MS et al. N Engl J Med 2017; 376:

13 Fourier Trial: MI/Stroke/CV Death 10% 9% 8% 7% 6% 5% 4% 3% 2% 1% Placebo Evolocumab 20% RRR NNT = 74 0% Months Sabatine MS et al. N Engl J Med 2017; 376: Pre-test ARS Question 8 In the ODYSSEY trial, what was the relative risk reduction in the primary outcome (major cardiovascular events) with alirocumab compared to placebo? 1. 5% 2. 15% 3. 25% 4. 35% 38 Odyssey Outcomes Trial Design 18,924 post ACS patients (1-12 months) Run-in period of 2-16 weeks on high-intensity or maximum tolerated dose of atorvastatin or rosvastatin At least one lipid entry criterion met RANDOMIZED Alirocumab SC Q2W DOUBLE BLIND Placebo SC Q2W ACC Scientific Sessions 2018 Follow-up: event driven 39 13

14 Odyssey Trial Lipid Results Upward drift likely due to protocol mandated discontinuation of therapy for LDL < 30 mg/dl ACC Scientific Sessions Odyssey Trial Primary Outcome RRR = 15% NNT = 63 ACC Scientific Sessions Odyssey: All Cause Mortality RRR = 15% NNT = 166 ACC Scientific Sessions

15 Indication Dosing How supplied Side effects Approved PCSK9 Inhibitors Alirocumab Evolocumab To reduce risk of CVE in adults with established CVD Adjunct to diet and maximumtolerated statin for adults with with other LLT, for adults with primary Adjunct to diet, alone or in combination HeFH or clinical ASCVD who hyperlipidemia (including HeFH) to require additional lowering reduce LDL-C of LDL-C Adjunct to diet and other LDL-lowering therapies in patients with HoFH who require additional lowering of LDL-C mg SQ Q2W 300 mg SQ monthly Single-dose prefilled pens or syringes 75-mg/mL or 150-mg/mL Nasopharyngitis Injection-site reactions Hypersensitivity reactions 140 mg SC Q2W 420 mg SC monthly Single-use prefilled syringe or autoinjector 1 ml of 140-mg/mL or 420 mg/3.5 ml Nasopharyngitis Injection-site reactions Hypersensitivity reactions Accessed May 8, Accessed May You will see lower LDL levels with PCSK-9 inhibitors than you ve ever seen before 44 FOURIER Trial Efficacy and Safety in Patients With LDL-C <10 mg/dl Cardiovascular Efficacy Safety LDL > 100 LDL < 10 LDL > 100 LDL < Percent (%) Percent (%) CVD, MI, Stroke, UA, Cor Revasc CVD, MI, Stroke 0 Serious AE AE (Drug Discontinued) 45 Giugliano RP, et al. Lancet. 2017;390(10106):

16 Even LDL-C levels < 10 appear to be safe (and efficacious) 46 When to Consider a PCSK9 Inhibitor Patient Type ASCVD without comorbidities LDL-C Reduction on Maximally Tolerated Statin <50% LDL-C reduction or LDL-C >70 mg/dl Therapy Recommendation Ezetimibe 1st; PCSK9 inhibitor 2nd ASCVD with comorbidities 21 years with ASCVD and baseline LDL-C 190 mg/dl 21 years without ASCVD and baseline LDL-C 190 mg/dl years without ASCVD and with DM and baseline LDL-C mg/dl years without ASCVD or DM and baseline LDL-C mg/dl <50% LDL-C reduction or LDL-C >70 mg/dl <50% LDL-C reduction or LDL-C >70 mg/dl <50% LDL-C reduction or LDL-C >100 mg/dl <50% LDL-C reduction or LDL-C >100 mg/dl <50% LDL-C reduction or LDL-C >100 mg/dl Ezetimibe * or PCSK9 inhibitor Ezetimibe* or PCSK9 inhibitor Ezetimibe* or PCSK9 inhibitor Ezetimibe or bile acid sequestrant Ezetimibe or bile acid sequestrant 47 Lloyd-Jones DM, et al. JACC. 2017;70(14) A Quantitative Approach to Adding Nonstatin Therapy 48 Robinson JG, et al. JACC. 2016;68(22):

17 A Quantitative Approach to Adding Nonstatin Therapy Very high risk: >30% 10-year ASCVD risk Clinical ASCVD + diabetes Clinical ASCVD + familial hypercholesterolemia Clinical ASCVD + poorly controlled risk factors Recent acute coronary syndrome (<3 months) Clinical ASCVD + polyvascular disease Clinical ASCVD + age >65 years Clinical ASCVD + multiple recurrent events Clinical ASCVD + elevated Lp(a) High risk: 20%-<30% 10-year ASCVD risk Clinical ASCVD without high-risk features Familial hypercholesterolemia Moderate risk: 10%-<20% 10-year ASCVD risk With or without DM Robinson JG, et al. JACC. 2016;68(22): Access to PCSK9 Inhibitors Baum et al. (44,234 prescriptions) 1-83% of PCSK9 inhibitor prescription rejected initially; 57% rejected ultimately - Patients with PCSK9 prescriptions approved were more likely to be on high-intensity statin + ezetimibe Navar et al. (prescriptions for 45,029 patients) 2-79% rejected within 24 hours; 53% rejected ultimately - Rejection rates: 33% 78% for commercial payers; 38% 84% for government insurance programs; 33% 75% across PBMs - 35% of filled prescriptions were abandoned at the pharmacy 1. Baum SJ, et al. Presented at the 66 th Scientific Session of the ACC, Washington, DC, March 17-19, Abstract Navar AM, et al. Presented at the 66 th Scientific Session of the ACC, Washington, DC. March 17-19, Abstract PCSK9 Inhibitor Support Programs Alirocumab programs 1 - Copay cards for $0 per month with annual cap of $5,500 for eligible patients with commercial insurance - Low income subsidy program for Medicare patients - Patient assistance program to provide free medication to eligible patients for up to 12 months which can be renewed - Insurance specialist available to assist with prior authorization Evolocumab programs 2 - Copay card $5 for eligible patients with commercial insurance - Insurance specialist available to offer assistance with coverage issues 1. Accessed September 18, Accessed May 18,

18 Common Reasons for PCSK9 Denial: A Veritable Laundry List Patient has not tried ezetimibe Re-challenge with statin not documented in statin-intolerant patient Patient has not tried a bile acid sequestrant LDL <100 mg/dl with ASCVD or <130 mg/dl without ASCVD Requires 80% compliance in fill history from pharmacy over 12-month period Nutrition intervention not documented Triglycerides >400 mg/dl Kaufman TM, Duell PB, et al. Circ Res. 2017;121(5): Common Reasons for PCSK9 Denial: A Veritable Laundry List Exercise and weight management regimen not documented Requires confirmation of FH with genetic testing Criteria for definite FH not documented Indication for PCSK9 inhibitor not clearly documented Failure to submit office notes or labs with prior authorization request No statement that patient will continue to receive maximally tolerated statin ASCVD criteria not met Kaufman TM, Duell PB, et al. Circ Res. 2017;121(5): Required Documentation for PCSK9 Prior Authorization (PA) Detailed medical history including prior and current medications, doses, dates of administration, reasons for discontinuation Family history of hypercholesterolemia and/or CAD Physical exam for xanthomas and DLCN score (for patients with FH) AHA criteria for diagnosis of FH Kaufman TM, Duell PB, et al. Circ Res. 2017;121(5):

19 Required Documentation for PCSK9 Prior Authorization (PA) Most recent lab results ( 30 days) including lipid panel and lipoprotein (a) Highest documented LDL-C concentration (ideally off treatment) Evidence of subclinical atherosclerosis (coronary artery calcium, CIMT, ankle brachial index) or clinical ASCVD (MI, stroke, angina, angiographic evidence, ischemia testing, arterial revascularization) Clear specification of diagnosis for which PCSK9 inhibitor therapy is being prescribed Kaufman TM, Duell PB, et al. Circ Res. 2017;121(5): Pre-test ARS Question 9 Which of the following strategies has demonstrated high rates of approval for the use of PCSK9 inhibitors? 1. Partner with prior-approval consultants 2. Discontinue use of other non-statin therapies prior to prescribing PCSK9 inhibitor 3. Employ multidisciplinary team to coordinate approval process 4. Refer patients to center with extensive experience with PCSK9 inhibitors 56 Strategies to Improve PCSK9 Inhibitor Access: A Team-Based Approach Have dedicated team to deal with prior authorizations, appeals, re-appeals, and peer-to-peer reviews Multidisciplinary team of physicians, a nurse, a medical assistant, a clinical pharmacist, and a physician assistant (the PCSK9 inhibitor Clinic ) - Coordinator oversees the approval process, provides injection training, and arranges longitudinal management and surveillance - 92% success rate (n=142/153) Key to successful PCSK9 inhibitor PA approval Meticulous documentation of all data required for PA Kaufman TM, Duell PB, et al. Circ Res. 2017;121(5):

20 ACC PSCK9 Prior Authorization Reporting Tool (PART) Available at: Accessed 5/7/18 58 Statins are still the mainstay of lipid-lowering therapy 59 Meta-analysis 14 Statin Trials (90,056 participants) For each 39 mg/dl LDL-C lowering with statins 12% reduction in all-cause mortality (P<0.0001) 19% reduction in coronary mortality (P<0.0001) 23% reduction in MI and coronary death (P<0.0001) 24% reduction in revascularizations (P<0.0001) 17% reduction in fatal or non-fatal stroke (P<0.0001) 21% reduction in any major vascular event (P<0.0001) Adapted from Baigent C et al. Cholesterol Treatment Trialists (CTT) Collaborators. Lancet 2005; 366:

21 Nonadherence to Statin Treatment Begins Early Adapted from cohort study in Ontario, Canada (N=85,020) Jackevicius et al. JAMA. 2002;288: Patients Non-adherent to Statin Therapy Have Poorer Outcomes Adherent Nonadherent Patients With MI (%) P= P= P= Total Blackburn DF, et al. Pharmacotherapy. 2005;25: Patients <65 Years Patients 65 Years 62 Patients should know that nonadherence to statin therapy may be associated with significant morbidity 63 21

22 Hyperlipidemia LDL-C is the target of lipid therapy and statins are the mainstay of treatment Response to statins is variable and influenced by many factors including genetic factors New therapies are emerging for treatment of hyperlipidemia Patient populations at highest CHD risk may potentially benefit greatly from such therapies 64 POST-TEST QUESTIONS 65 Post-test ARS Question 1 After completing this activity, how confident are you now in your ability to determine which patients may benefit from use of a PCSK9 inhibitor? 1. Not at all confident 2. Slightly confident 3. Moderately confident 4. Pretty much confident 5. Very confident 66 22

23 Post-test ARS Question 2 After completing this activity, how often do you now intend to consider non-statin therapies for patients with high ASCVD risk and LDL-C not at recommended target, despite use of maximally tolerated statin? 1. Never 2. Rarely 3. Sometimes 4. Frequently 5. Always 67 Post-test ARS Question 3 70-year-old woman, 15-year history of hypertension, 10- year history of dyslipidemia NSTEMI 1 year ago, LDL-C is 88 mg/dl Current medications include lisinopril/hydrochlorothiazide 40/25 mg qd, metoprolol tartrate 100 mg bid, rosuvastatin 40 mg qd, and aspirin 81 mg qd After reviewing the brief scenario above, please rate this statement as consistent with or not consistent with best clinical practice: Switch to atorvastatin 80 mg: 1. Yes, it is consistent 2. No, it is not consistent 68 Post-test ARS Question 4 70-year-old woman,15-year history of hypertension, 10- year history of dyslipidemia NSTEMI 1 year ago, LDL-C is 88 mg/dl Current medications include lisinopril/hydrochlorothiazide 40/25 mg qd, metoprolol tartrate 100 mg bid, rosuvastatin 40 mg qd, and aspirin 81 mg qd After reviewing the brief scenario above, please this statement as consistent with or not consistent with best clinical practice: Add ezetemibe: 1. Yes, it is consistent 2. No, it is not consistent 69 23

24 Post-test ARS Question 5 70-year-old woman,15-year history of hypertension, 10-year history of dyslipidemia NSTEMI 1 year ago, LDL-C is 88 mg/dl Current medications include lisinopril/hydrochlorothiazide 40/25 mg qd, metoprolol tartrate 100 mg bid, rosuvastatin 40 mg qd, and aspirin 81 mg qd Ezetimibe is added. Six months later, LDL-C is 72 mg/dl. After reviewing the brief scenario above, please rate this statement as consistent with or not consistent with best clinical practice: Add PCSK9 inhibitor: 1. Yes, it is consistent 2. No, it is not consistent 70 Post-test ARS Question 6 In the FOURIER trial, what was the numberneeded-to-treat to prevent an instance of the primary outcome (major cardiovascular events) with evolocumab compared to placebo? Post-test ARS Question 7 In the ODYSSEY trial, what was the relative risk reduction in the primary outcome (major cardiovascular events) with alirocumab compared to placebo? 1. 5% 2. 15% 3. 25% 4. 35% 72 24

25 Post-test ARS Question 8 Which of the following strategies has demonstrated high rates of approval for the use of PCSK9 inhibitors? 1. Partner with prior-approval consultants 2. Discontinue use of other non-statin therapies prior to prescribing PCSK9 inhibitor 3. Employ multidisciplinary team to coordinate approval process 4. Refer patients to center with extensive experience with PCSK9 inhibitors 73 Questions 74 25