DYSLIPIDEMIA TREATMENT: HYBRIDIZING CLINICAL PRACTICE GUIDELINES

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1 DYSLIPIDEMIA TREATMENT: HYBRIDIZING CLINICAL PRACTICE GUIDELINES SATURDAY/4:30-5:30PM ACPE UAN: L01-P 0.1 CEU/1.0 hr Activity Type: Knowledge-Based Learning Objectives for Pharmacists: Upon completion of this CPE activity participants should be able to: 1. Review different methods for risk stratifying patients with dyslipidemia 2. Compare and contrast lipid targets with fixed statin dosing based on risk 3. Determine situations when non-statin lipid-lowering agents will provide most benefit and least risk 4. Discuss how lipid lowering therapy should be adjusted based on laboratory monitoring Speaker: Sean Stewart, PharmD, BCACP, CLS Sean Stewart is a pharmacist practicing in comprehensive medication management services at Park Nicollet. He received his PharmD degree in 2009 from the University of Minnesota and completed a residency in ambulatory care at Essentia Health in Duluth, MN in He is a certified ambulatory care pharmacist from the Board of Pharmaceutical Specialties and a certified lipid specialist from the Accreditation Council for Clinical Lipidology. Speaker Disclosure: Sean Stewart reports no actual or potential conflicts of interest in relation to this CPE activity. Off-label use of medications will not be discussed during this presentation.

2 Dyslipidemia Treatment: Hybridizing Clinical Practice Guidelines Sean Stewart, Pharm.D, BCACP, CLS Clinical Pharmacist Medication Management Park Nicollet Health Services Disclosure Dr. Stewart reports no actual or potential conflicts of interest associated with this presentation, OR 1

3 Learning Objectives Upon successful completion of this activity, participants should be able to: - Review different methods for risk stratifying patients with dyslipidemia - Compare and contrast fixed lipid targets with fixed-statin dosing based on risk - Determine situations where non-statin lipid-lowering agents will provide most benefit and least risk - Discuss how lipid-lowering therapy should be adjusted based on laboratory monitoring Stone NJ, et al. J Am Coll Cardiol. 2014;63:

4 ACC/AHA Guideline RCTs identified in a systematic evidence review compared either fixed doses of statins with placebo or fixed doses of higher-intensity statins with moderate-intensity statins No RCT evidence to support titrating cholesterol-lowering drug therapy to achieve target LDL-C levels Extensive RCT evidence that the appropriate intensity of statin therapy should be used to reduce ASCVD risk in those most likely to benefit Stone NJ, et al. J Am Coll Cardiol. 2014;63: ACC/AHA Guideline: Statin Benefit Groups Decreasing Level of Baseline Absolute Risk Clinical ASCVD (ACS, h/o MI, angina, revascularization, stroke, TIA, or PAD) Primary LDL-C 190 mg/dl Diabetes, age 40-75, and LDL-C mg/dl No ASCVD or diabetes, LDL-C mg/dl and 10-year ASCVD risk 7.5% ACS = acute coronary syndrome; MI = myocardial infarction; TIA = transient ischemic attack; PAD = peripheral arterial disease Stone NJ, et al. J Am Coll Cardiol. 2014;63(25):

5 ACC/AHA Guideline: Intensity of Statin Treatment Matched to Risk Clinical ASCVD*, age years Statin Benefit Group Primary LDL-C 190 mg/dl, age 21 years Diabetes, LDL-C mg/dl, age years 7.5% 10-year ASCVD risk** < 7.5% 10-year ASCVD risk No Clinical ASCVD or Diabetes, LDL-C mg/dl, age years 7.5% 10-year ASCVD risk 5 to < 7.5% 10-year ASCVD risk Intensity of Statin Treatment High High High Moderate Moderate to High Consider Moderate *Clinical ASCVD = acute coronary syndrome, angina, revascularization, stroke/tia, peripheral vascular disease **ASCVD Risk = nonfatal MI, nonfatal stroke, or death due to cardiovascular cause calculated using Pooled Cohort Equations calculator Stone NJ, et al. J Am Coll Cardiol. 2014;63(25): ACC/AHA Guideline: Classifications of Statin Intensity High-Intensity Statin Therapy (lowers LDL-C by approx. 50%) Atorvastatin mg Rosuvastatin mg Moderate-Intensity Statin Therapy (lowers LDL-C by approx %) Atorvastatin mg Rosuvastatin 5-10 mg Simvastatin mg Pravastatin mg Lovastatin 80 mg Fluvastatin XL 80 mg Fluvastatin 40 mg BID Pitavastatin 2-4 mg Low-Intensity Statin Therapy (lowers LDL-C by approx. < 30%) Simvastatin 10 mg Pravastatin mg Lovastatin 20 mg Fluvastatin mg Pitavastatin 1 mg Stone NJ, et al. J Am Coll Cardiol. 2014;63(25):

6 ACC/AHA Guideline: Additional Factors to Consider to Inform Decision Making Primary LDL-C 160 mg/dl Family History of Premature ASCVD Lifetime ASCVD Risk CAC Score > 300 Agatston Units or > 75 th Percentile ABI < 0.9 hscrp > 2.0 mg/l Stone NJ, et al. J Am Coll Cardiol. 2014;63(25): Jacobson TA, et al. J Clin Lipidol. 2015;9:

7 NLA Recommendations Part 1 Lack of RCTs explicitly designed to test LDL-C/Non-HDL-C treatment goals does not invalidate the considerable evidence supporting them RCTs using various methods for lowering atherogenic cholesterol have indicated on-treatment LDL-C levels have been consistently associated with lower absolute risk for an ASCVD event Treatment goals facilitate effective communication between patients and clinicians improving progress towards meeting treatment objectives and supporting efforts to maximize long-term adherence Jacobson TA, et al. J Clin Lipidol. 2015;9: NLA Recommendations Part 1: LDL Treatment Targets Matched to Level of Risk Risk Category Criteria Treatment Goal Consider Drug Therapy LDL-C Non-HDL-C LDL-C Non-HDL-C Low 0-1 major ASCVD risk factors < 100 < Moderate High Very High 2 major ASCVD risk factors Consider quantitative risk scoring Consider other risk indicators 3 major ASCVD risk factors Diabetes and 0-1 other major ASCVD risk factors CKD stage 3B or 4 LDL-C 190 mg/dl Quantitative risk score 15% ASCVD Diabetes and 2 other major ASCVD risk factors Evidence of end-organ damage < 100 < < 100 < < 70 < Jacobson TA, et al. J Clin Lipidol. 2015;9:

8 NLA Recommendations Part 1: Major ASCVD Risk Factors Age Family History of Early CHD Male > 45 years Female > 55 years First-degree male < 55 years First-degree female < 65 years Cigarette Smoking Blood Pressure Low HDL-C 140/90 mmhg Treated with antihypertensive medication Male < 40 mg/dl Female < 50 mg/dl Jacobson TA, et al. J Clin Lipidol. 2015;9: NLA Recommendations: Additional Risk Indicators Metabolic Syndrome Severe Major ASCVD Risk Factor Primary LDL-C 160 mg/dl (or non-hdl-c 190 mg/dl) hscrp 2.0 mg/l Lipoprotein (a) 50 mg/dl Urine albumin-tocreatinine ratio 30 mg/g Jacobson TA, et al. J Clin Lipidol. 2015;9:

9 Jacobson TA, et al. J Clin Lipidol. 2015;9:S1-S122 NLA Recommendations Part 2 Purpose to expand upon the NLA part 1 recommendations in areas where clinicians may desire additional guidance Focus on areas where evidence base is less robust or is lacking results from RCTs on clinical ASCVD events to guide decisions Jacobson TA, et al. J Clin Lipidol. 2015;9:S1-S122 8

10 NLA Recommendations Part 2: Focus Areas Lifestyle Therapies The Lifespan Nutrition and exercise/physical activity Children to seniors; Pregnancy to menopause Ethnic Groups Groups with Increased Risk African Americans, Hispanics/Latinos, South Asians, American Indians/Alaska Natives Human Immunodeficiency Virus (HIV), rheumatological disease, and high residual risk despite statin therapy Jacobson TA, et al. J Clin Lipidol. 2015;9:S1-S122 Lloyd-Jones DM, et al. J Am Coll Cardiol. 2017;70:

11 ACC Expert Clinical Decision Pathway In what patient populations should non-statin therapies be considered? In what situations should non-statin therapies be considered? If non-statin therapies are to be added, which agents or therapies should be considered and in what order? Lloyd-Jones DM, et al. J Am Coll Cardiol. 2017;70: Lloyd-Jones DM, et al. J Am Coll Cardiol. 2017;70:

12 ACC Expert Clinical Decision Pathway: Patient Populations to Consider Non-Statins ASCVD with comorbidities ASCVD without comorbidities ASCVD and baseline LDL-C 190 No ASCVD and baseline LDL-C 190 Age without ASCVD and diabetes Age without ASVD or diabetes and 10-year risk 7.5% Lloyd-Jones DM, et al. J Am Coll Cardiol. 2017;70: ACC Expert Clinical Decision Pathway: Comorbidities Recent ASCVD event ASCVD event while taking a statin Poorly controlled other ASCVD risk factors Elevated lipoprotein (a) CKD Symptomatic heart failure Maintenance hemodialysis Baseline LDL-C 190 mg/dl Residual coronary artery disease Metabolic syndrome Age 65 years Prior MI or non-hemorrhagic stroke Current daily cigarette smoking Symptomatic PAD with prior history of MI or stroke History of non-mi-related coronary revascularization Low HDL-C (< 40 mg/dl in males and < 50 mg/dl in females) hscrp > 2 mg/l Lloyd-Jones DM, et al. J Am Coll Cardiol. 2017;70:

13 JelliingerPS, et al. Endocr Pract. 2017;23 (Suppl 2):1-87 AACE Guideline Dyslipidemia is a primary, major risk factor for ASCVD and may even be a prerequisite for ASCVD, occurring before other risk factors come into play This guideline extends and updates existing clinical practice guidelines in the literature. JelliingerPS, et al. Endocr Pract. 2017;23 (Suppl 2):

14 AACE Guidelines: Treatment Goals Based on Risk Risk Category Criteria Treatment Goal Consider Drug Therapy LDL-C Non-HDL-C LDL-C Non-HDL-C Low 0-1 major ASCVD risk factors < 100 < Moderate High Very High Extreme 2 major ASCVD risk factors and 10- year risk < 10% 3 major ASCVD risk factors and 10- year risk 10-20% Diabetes or CKD 3/4 with no other risk factors ASCVD Diabetes or CKD 3/4 with 1 other major ASCVD risk factors Heterozygous FH Progressive ASCVD after achieving LDL-C 190 mg/dl Established ASCVD in patient with DM, CKD 3/4, or heterozygous FH History of premature ASCVD (<55 male, <65 female) JelliingerPS, et al. Endocr Pract. 2017;23 (Suppl 2):1-87 < 100 < < 100 < < 70 < < 55 < Patient Case #1: Patient with HIV 40-year-old white male diagnosed with HIV six years ago after admission to hospital with fevers. He has been on antiretroviral medication since that time. His viral load and CD4 counts He has no personal history of CVD or family history of premature CAD. He follows a Mediterranean Diet, does not smoke, has a glass of wine with dinner and denies use of illicit drugs. He engages in no regular exercise but walks to and from work (2 miles each way) as a school teacher. 13

15 Patient Case #1 (continued) Medical History: HIV, Hypertension, dyslipidemia (attempting to control by diet). Exam: BMI 27 BP 132/75 Waist circumference 42 inches Fasting Lipid Profile: Total cholesterol 232 LDL-C 150 Triglycerides 250 HDL-C 32 Non-HDL-C 200 Patient Case #1 (continued) Medications: Complera one tablet daily Emtricitabine 200 mg Rilpivirine 25 mg Tenofovir disoproxil fumarate 300 mg Hydrochlorothiazide 12.5 mg daily Lisinopril 10 mg daily 14

16 Polling Question 1 Patient Case #1 (continued) ASCVD Risk Scoring Age 40 years Sex Male Race White Total Cholesterol 232 HDL-C 32 SBP 132 Treatment for HTN? Yes History of Diabetes? No Smoker? No Current 10-Year ASCVD Risk = 3.5% 15

17 Patient Case #1 (continued) Using ACC/AHA guideline, patient in case #1 would have a 10-year ASCVD risk of 3.5%. Since this is below the threshold of 5-7.5%, he would not be a candidate for a statin His primary LDL-C is less than 160 mg/dl and there is no data on other risk indicators. This does not help us in additional risk stratification Is it acceptable then for patient to continue with diet and exercise until his risk does indicate starting a statin? Estimating ASCVD Risk in Patients with HIV using ACC/AHA and Framingham 108 HIV-infected patients without known CVD and not on lipid-lowering therapy underwent CT angiography Plaque characterized as having high-risk morphology (HRM) ACC/AHA guidelines compared with NCEP ATP III guidelines in terms of who would be treated with a statin High-Risk Morphology (HRM) ACC/AHA Framingham Yes 26% 10% No 19% 7% Zanni MV, et al. AIDS. 2014;28:

18 How Good is the Pooled Cohorts Equation Calculator in HIV Effectiveness of PCE at Predicting Risk Effectiveness of PCE at Predicting ASCVD Events Overall Good Poor White Men Good Poor Black Men Good Poor White Women Same as Random Chance Poor Black Women Good Poor Feinstein MJ, et al. JAMA Cardiol. 2017;2: NLA Recommendations Part 2 Lifestyle Therapies The Lifespan Nutrition and exercise/physical activity Children to seniors; Pregnancy to menopause Ethnic Groups Groups with Increased Risk African Americans, Hispanics/Latinos, South Asians, American Indians/Alaska Natives Human Immunodeficiency Virus (HIV), rheumatological disease, and high residual risk despite statin therapy Jacobson TA, et al. J Clin Lipidol. 2015;9:S1-S122 17

19 NLA Recommendations Part 2: Section on Patients with Human Immunodeficiency Virus There has not been sufficient research to formulate validated risk-stratification schemes for HIV-infected patients For primary prevention of ASCVD, HIV infection may be counted as an additional ASCVD risk factor for risk stratification Initial risk stratification is based on the number of ASCVD risk factors (with the caveat that HIV infection may be counted as an additional risk factor), use of risk prediction tools, and the use of clinical indicators if needed NLA Recommendations Part 1: Major ASCVD Risk Factors Age Family History of Early CHD Male > 45 years Female > 55 years First-degree male < 55 years First-degree female < 65 years Cigarette Smoking Blood Pressure Low HDL-C Additional ASCVD Risk Factors 140/90 mmhg Treated with antihypertensive medication Male < 40 mg/dl Female < 50 mg/dl Presence of HIV Infection 18

20 NLA Recommendations Risk Category Criteria Treatment Goal Consider Drug Therapy LDL-C Non-HDL-C LDL-C Non-HDL-C Low 0-1 major ASCVD risk factors < 100 < Moderate High Very High 2 major ASCVD risk factors Consider quantitative risk scoring Consider other risk indicators 3 major ASCVD risk factors Diabetes and 0-1 other major ASCVD risk factors CKD stage 3B or 4 LDL-C 190 mg/dl Quantitative risk score 15% ASCVD Diabetes and 2 other major ASCVD risk factors Evidence of end-organ damage < 100 < < 100 < < 70 < Jacobson TA, et al. J Clin Lipidol. 2015;9: Patient Case #1 (continued) Using NLA recommendations, patient would be a candidate for a statin A high-intensity statin should be chosen; however, need to factor in potential drug-drug interactions with patient s antiretroviral therapy, if applicable LDL-C target is less than 100 mg/dl 19

21 Patient Case #2 57-year-old Caucasian female referred to MTM for follow-up of hypertension Past Medical History: Diagnosed with hypertension and hyperlipidemia 3 months ago by PCP. Started on losartan 50 mg daily and atorvastatin 20 mg daily Social History: Recently started a new job working for an insurance company. The company has incentivized her to improve her health. She is now exercising 4 days per week and eating better. Patient Case #2 (continued) Family History: Father had MI and coronary artery bypass surgery at age 54 Current Medications (reports full adherence): Atorvastatin 20 mg daily Losartan/hydrochlorothiazide 50/12.5 mg daily Other Assessments: 10-Year ASCVD Risk = 8.5% 20

22 Patient Case #2 (continued) Labs Total Cholesterol HDL-Cholesterol Triglycerides LDL-Cholesterol 3 Months Ago Today Vitals Blood Pressure Weight 3 Months Ago 146/ Today 124/ Polling Question 2 21

23 Polling Question 3 ACC/AHA Guideline Clinical ASCVD*, age years Statin Benefit Group Primary LDL-C 190 mg/dl, age 21 years Diabetes, LDL-C mg/dl, age years 7.5% 10-year ASCVD risk** < 7.5% 10-year ASCVD risk No Clinical ASCVD or Diabetes, LDL-C mg/dl, age years 7.5% 10-year ASCVD risk 5 to < 7.5% 10-year ASCVD risk Intensity of Statin Treatment High High High Moderate Moderate to High Consider Moderate Following the ACC/AHA guidelines, this patient is on an appropriate statin; however, has not had the expected 30-50% reduction in LDL-C (patient s change ~15%) 22

24 Progression of Atherosclerosis in Statin Hyporesponders Hyporesponders defined as percentage reduction in LDL-C of < 15% Kataoka Y, et al. Arterioscler Thromb Vasc Biol. 2015;35: NLA Recommendations Part 1: Major ASCVD Risk Factors Age Family History of Early CHD Male > 45 years Female > 55 years First-degree male < 55 years First-degree female < 65 years Cigarette Smoking Blood Pressure Low HDL-C 140/90 mmhg Treated with antihypertensive medication Male < 40 mg/dl Female < 50 mg/dl Jacobson TA, et al. J Clin Lipidol. 2015;9:

25 NLA Recommendations Part 1 Risk Category Criteria Treatment Goal Consider Drug Therapy LDL-C Non-HDL-C LDL-C Non-HDL-C Low 0-1 major ASCVD risk factors < 100 < Moderate High Very High 2 major ASCVD risk factors Consider quantitative risk scoring Consider other risk indicators 3 major ASCVD risk factors Diabetes and 0-1 other major ASCVD risk factors CKD stage 3B or 4 LDL-C 190 mg/dl Quantitative risk score 15% ASCVD Diabetes and 2 other major ASCVD risk factors Evidence of end-organ damage < 100 < < 100 < < 70 < Jacobson TA, et al. J Clin Lipidol. 2015;9: ACC Expert Clinical Decision Pathway: Patient Populations to Consider Non-Statins ASCVD with comorbidities ASCVD without comorbidities ASCVD and baseline LDL-C 190 No ASCVD and baseline LDL-C 190 Age without ASCVD and diabetes Age without ASVD or diabetes and 10-year risk 7.5% Lloyd-Jones DM, et al. J Am Coll Cardiol. 2017;70:

26 1 2 3 Lloyd-Jones DM, et al. J Am Coll Cardiol. 2017;70: HIGH-RISK MARKERS 10-year ASCVD risk 20% Baseline LDL-C 160 mg/dl Poorly controlled other ASCVD risk factor Family history Evidence of accelerated subclinical atherosclerosis Elevated hs-crp Other risk modifying condition (CKD, HIV, RA, etc) HIGH-RISK MARKERS 10-year ASCVD risk 20% Baseline LDL-C 160 mg/dl Poorly controlled other ASCVD risk factor Family history Evidence of accelerated subclinical atherosclerosis Elevated hs-crp Other risk modifying condition (CKD, HIV, RA, etc) Lloyd-Jones DM, et al. J Am Coll Cardiol. 2017;70:

27 7 Lloyd-Jones DM, et al. J Am Coll Cardiol. 2017;70: Patient Case #2 Summary Patient started on appropriate statin dose according to level of ASCVD risk per ACC/AHA guideline; however, did not have an expected response Using NLA Recommendations Part 1, patients LDL-C goal is < 100 mg/dl Using the ACC Expert Clinical Decision Pathway for primary prevention patients taking a statin, the next step after lifestyle modifications addressed would be to switch to highpotency statin 26

28 Patient Case #3 40-year-old male referred to preventive cardiology clinic for aggressive risk factor management Past Medical History: Hospitalized for STEMI at age 36, received drug-eluting stent. Started on atorvastatin 80 mg daily. Hospitalized again at age 38 for NSTEMI and received 3-vessel CABG. Atorvastatin 80 mg changed to rosuvastatin 40 mg daily Social History: Married with three children. Works as CPA for financial advisement firm. Minimal exercise other than coaching his children in gymnastics. Drinks socially Patient Case #3 (continued) Family History: Father with MI at 43 years old then bypass surgery at age 48. Very high cholesterol on all sides of his family, more on his father s. He doesn t recall any specific values Current Medications Rosuvastatin 40 mg daily Aspirin 81 mg daily Empagliflozoin/metformin ER 25/1000 mg daily Valsartan 160 mg daily Metoprolol succinate 50 mg daily 27

29 Patient Case #3 (continued) Labs Baseline: Recalls TC 295 (LDL-C was 227 mg/dl) Current: LDL-C 102 mg/dl Vitals BP 119/77; P 72 Weight 160 lbs (baseline 190 lbs) Polling Question 4 28

30 Polling Question 5 ACC/AHA Guideline Clinical ASCVD*, age years Statin Benefit Group Primary LDL-C 190 mg/dl, age 21 years Diabetes, LDL-C mg/dl, age years 7.5% 10-year ASCVD risk** < 7.5% 10-year ASCVD risk No Clinical ASCVD or Diabetes, LDL-C mg/dl, age years 7.5% 10-year ASCVD risk 5 to < 7.5% 10-year ASCVD risk Intensity of Statin Treatment High High High Moderate Moderate to High Consider Moderate Following the ACC/AHA guidelines, this patient is adequately treated; however, can/should we do more to reduce this patient s risk for future events? 29

31 Relationship between on-treatment LDL-C levels and CHD events in secondary prevention Examinations of on-treatment LDL-C concentration with CHD events show strong positive correlation This relationship is present across the full spectrum of LDL- C levels Jacobson TA, et al. J Clin Lipidol. 2015;9: Risk Category Criteria AADE Guideline Treatment Goal Consider Drug Therapy LDL-C Non-HDL-C LDL-C Non-HDL-C Low 0-1 major ASCVD risk factors < 100 < Moderate High Very High Extreme 2 major ASCVD risk factors and 10- year risk < 10% 3 major ASCVD risk factors and 10- year risk 10-20% Diabetes or CKD 3/4 with no other risk factors ASCVD Diabetes or CKD ¾ with 1 other major ASCVD risk factors Heterozygous FH Progressive ASCVD after achieving LDL-C < 100 mg/dl Established ASCVD in patient with DM, CKD 3/4, or heterozygous FH History of premature ASCVD (<55 male, <65 female) JelliingerPS, et al. Endocr Pract. 2017;23 (Suppl 2):1-87 < 100 < < 100 < < 70 < < 55 <

32 ACC Expert Clinical Decision Pathway (ECDP) on Role of Non-Statins ASCVD with comorbidities ASCVD without comorbidities ASCVD and baseline LDL-C 190 No ASCVD and baseline LDL-C 190 Age without ASCVD and diabetes Age without ASVD or diabetes and 10-year risk 7.5% Lloyd-Jones DM, et al. J Am Coll Cardiol. 2017;70: ACC Expert Clinical Decision Pathway: Comorbidities Diabetes Recent (< 3 mos) ASCVD event ASCVD event while taking a statin Poorly controlled other ASCVD risk factors Elevated lipoprotein (a) CKD Symptomatic heart failure Maintenance hemodialysis Baseline LDL-C 190 mg/dl Residual coronary artery disease Age 65 years Prior MI or non-hemorrhagic stroke Current daily cigarette smoking Symptomatic PAD with prior history of MI or stroke History of non-mi-related coronary revascularization Low HDL-C (< 40 mg/dl in males and < 50 mg/dl in females) hscrp > 2 mg/l Metabolic syndrome Lloyd-Jones DM, et al. J Am Coll Cardiol. 2017;70:

33 Lloyd-Jones DM, et al. J Am Coll Cardiol. 2017;70: Guidance on Use of Ezetimibe or PCSK9 Inhibitors Ezetimibe Patients at very-high risk (clinical ASCVD or familial hypercholesterolemia) unable to achieve 50% reduction in LDL-C or target levels* on maximally tolerated statin Less additional LDL-C reduction is required to reach target/goal (up to 25%) Insurance coverage is a concern PCSK9 Inhibitors Patients at very-high risk (clinical ASCVD or familial hypercholesterolemia) unable to achieve 50% reduction in LDL-C or target levels* on maximally tolerated statin More additional LDL-C reduction is required to reach target/goal (> 25%) Insurance coverage is not a concern Lloyd-Jones DM, et al. J Am Coll Cardiol. 2017;70:

34 Clinical Benefit of Evolocumab in Select Subgroups: Analysis from FOURIER Subgroup Rate of CV Death/MI/Stroke Placebo Evolocumab Relative Risk Reduction Absolute Risk Reduction Number Needed to Treat Overall 9.9% 7.9% 20% 2.0% 50 Qualifying MI < 2 years ago Qualifying MI 2 years ago 10.8% 7.9% 24% 2.9% % 8.3% 13% 1.0% Prior MIs 15.0% 12.4% 21% 2.6% 38 < 2 Prior MIs 8.2% 6.6% 16% 1.7% 60 Multivessel Disease No Multivessel Disease 12.6% 9.2% 30% 3.4% % 7.6% 11% 1.3% 78 Sabatine MS, et al. Clinical benefit of evolocumab in patients with a history of MI: An analysis from FOURIER. American Heart Association 2017 Scientific Sessions. November 13, 2017; Anaheim, CA Patient Case #3 Summary Patient treated with appropriate statin dose per ACC/AHA guideline; however, is still at high risk based on multiple risk factors Using the 2017 AACE guidelines, the patient would qualify for an LDL-C goal of < 55 mg/dl. This is consistent with results from IMPROVE-IT and FOURIER studies Using the ACC Expert Clinical Decision Pathway, ezetimibe or a PCSK9 inhibitor could be used to further lower LDL-C and reduce ASCVD events A PCSK9 inhibitor may be more appropriate given that > 25% reduction in LDL-C is needed to achieve goal and that patient has multitude of factors which make PCSK9 inhibitor more cost effective 33

35 Questions? 34