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Adverse Impacts of Severe ASCVD Is PCSK9 Inhibition the Key to Improving Patient Outcomes?

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Adverse I m pacts of Severe ASCVD:

I s PCSK9 I nhibition the Key to I m proving Patient Outcom es?

Eliot A. Brinton, MD, FAHA, FNLA President, Utah Lipid Center Salt Lake City, Utah Past President, American Board of Clinical Lipidology

Educational Objectives

At the conclusion of this activity, participants should be able to:

• Evaluate the extent of residual CVD risk to which high-risk

patients are exposed

• Analyze the potential strengths and weaknesses of new

approaches to reduce CVD risk

• Incorporate insights about new LDL-lowering agents in

combination with statin therapy into more comprehensive clinical treatment strategies

• Discuss strategies to improve the knowledge, skills, or

performance of the healthcare team

Elevated LDL-C

Cardiovascular Pathobiology

80 100 120 140 160 180 LDL-C (mg/dL) 4.50 2.85 1.80 1.15 0.75 Relative Risk of CHD Women n=6907 Men n=5432

Adjusted for age and race 10-year follow-up

ARI C Study: Relationship of LDL-C to CHD

Sharrett AR et al. Circulation. 2001;104:1108–1113.

Support for LDL Causality in ASCVD

• Four Compelling Lines of Evidence:
• Observational data
• Interventional data
• Genetic studies
• Experimental data

ASCVD = atherosclerotic cardiovascular disease

Khera AV et al. J Am Coll Cardiol. 2016;67:2578-2589.

I m pact of Hypercholesterolem ia Mutation Status on CAD According to LDL-C Level

FH mutations included loss‐of‐function variants in LDLR, missense mutations in LDLR predicted to be damaging, and variants linked to FH

LDL Cholesterol Category (mg/dL)

Adverse Impacts of Severe ASCVD Is PCSK9 Inhibition the Key to Improving Patient Outcomes?

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Unadjusted Rates of CHD Death or Nonfatal MI per 1 0 0 0 Person-years and Underlying Observed Event Num bers in Men and W om en w ith FH

Perak AM et al. Circulation. 2016;134:9-19.

LDL-C Reduction: Cardiovascular Benefits

Mean Attained LDL-C on Statin Therapy and Risks of Secondary Cardiovascular Events

Boekholdt SM et al. J Am Coll Cardiol. 2014;64:485-494.

Genetically and Pharm acologically Mediated Reduction of LDL-C Low ers Risk of CHD

Ference BA et al. J Am Coll Cardiol. 2015;65:1552-1561.

Patients w ho Achieve Very Low LDL-C Levels have Low er Risk For MACE

Boekholdt SM et al. J Am Coll Cardiol. 2014;64:485-494.

When LDL-C is reduced to 50 mg/dL or lower, the risk for CV events is reduced by more than half.

LDL-C and Atherosclerotic Cardiovascular Disease

• Cumulative LDL arterial burden is a central determinant for the

initiation and progression of atherosclerotic cardiovascular disease

• The lower the LDL-C level attained by agents that primarily target

LDL receptors, the greater the clinical benefit

• Both relative and absolute risk reduction relate to the magnitude
• f LDL-C reduction
• Lowering LDL-C in individuals at high cardiovascular risk earlier

rather than later appears advisable, especially in those with familial hypercholesterolemia

Eur Heart J. 2017 Apr 24. doi: 10.1093/eurheartj/ehx144. [Epub ahead of print].

Adverse Impacts of Severe ASCVD Is PCSK9 Inhibition the Key to Improving Patient Outcomes?

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Statins: The Gold Standard for LDL-C Reduction

Updated from O’Keefe J et al. J Am Coll Cardiol. 2004;43:2142-2146.

CHD Events Are Reduced Proportional to LDL-C Low ering w ith Statins

ACS and Other Secondary Prevention Trials

y = 0.1629x ∙ 4.6776 R² = 0.9029 P <0.0001 LDL Cholesterol (mg/dL) CHD Events (%)

PROVE‐IT‐PR PROVE‐IT‐AT CARE‐S LIPID-S HPS‐S 4S‐S HPS‐P CARE‐P LIPID‐P 4S‐P

5 10 15 20 25 30 30 50 70 90 110 130 150 170 190 210

TNT 80 TNT 10 A2Z 80 A2Z 20 IDEAL S20/40 IDEAL A80 High-intensity Statin Therapy Moderate-intensity Statin Therapy Low-intensity Statin Therapy Daily dose lowers LDL-C,

• n average, by

approximately ≥50% Daily dose lowers LDL-C,

• n average, by

approximately 30% to <50% Daily dose lowers LDL-C,

• n average, by

approximately <30% Atorvastatin 40*-80* mg Rosuvastatin 20*-40** mg Atorvastatin 10* (20**) mg Rosuvastatin (5**) 10* mg Simvastatin 20*-40* mg Pravastatin 40* (80**) mg Lovastatin 40* mg Fluvastatin XL 80** mg Fluvastatin 40 mg BID* Pitavastatin 2-4** mg Simvastatin 10** mg Pravastatin 10*-20* mg Lovastatin 20* mg Fluvastatin 20**-40** mg Pitavastatin 1** mg

High, Moderate, and Low -intensity Statin Therapy Used in Clinical Trials

FD

Stone NJ et al. Circulation. 2014;129(25 Suppl 2):S1-45. Goff DC et al. Circulation. 2014;129(25 Suppl 2):S49-73.

*Statins demonstrated reduction in major CVD events **FDA-approved doses not tested in clinical trials

2 0 1 3 ACC/ AHA Guideline: Treatm ent of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults

• Low-intensity statins are recommended only in patients with history of or at

risk for adverse drug effects

• Moderate-to-high-intensity statins recommended for patients with clinical

ASCVD and those with diabetes

• High-intensity statins recommended for patients with LDL-C >190 mg/dL
• Did not find evidence to support LDL-C thresholds or targets of therapy. No

evidence was found that titration or combination drug therapy to achieve specific LDL-C or non-HDL-C levels or percent reduction improved ASCVD

• utcomes. No dose titration recommended.
• Monitor LDL-C to assess compliance and response to therapy

HDL-C = high-density lipoprotein cholesterol

Stone NJ et al. Circulation. 2014;129(25 Suppl 2):S1-45. Goff DC et al. Circulation. 2014;129(25 Suppl 2):S49-73

ASCVD Statin Benefit Groups

No

Stone NJ et al. Circulation. 2013;129:S49-S73.

Statin Therapy: Monitoring Therapeutic Response and Adherence

Stone NJ et al. Circulation. 2013;129:S49-S73.

LDL Testing LDL Testing LDL Testing LDL Testing LDL Testing

Adverse Impacts of Severe ASCVD Is PCSK9 Inhibition the Key to Improving Patient Outcomes?

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Risk Category Criteria Initiate Drug Therapy Non‐HDL‐C (LDL‐C) (mg/dl) Treatment Goal Non‐HDL‐C (LDL‐C) (mg/dl) Low

• 0‐1 major RF*

>190 (>160) <130 (<100) Moderate

• At least 2 major RF and 10‐year risk

<10%* >160 (>130) <130 (<100) High

• At least 2 major RF and 10‐year risk

>10%

• At least 3 RF
• DM with 0‐1 other RFs and no end
• rgan damage
• CKD stage 3 or 4
• LDL‐C >190 mg/dl

>130 (>100)# <130 (<100) Very High

• Established ASCVD
• DM with at least 2 other RFs or end
• rgan damage

>100 (>70)# <100 (<70)

NLA Recom m endations: I nitiate Therapy Based on Risk and Lipid Levels and Treat to Specific Goal

*Consider other risk markers # Consider moderate or high intensity statin in patient with ASCVD or DM regardless of baseline lipid levels www.lipid.org

Residual CHD Risk Despite Statin Therapy

Major Statin Trials: Despite Benefit, Substantial Residual CV Risk Rem ains

4S1 LIPID2 CARE3 HPS4 WOSCOPS5 AFCAPS/ TexCAPS6 JUPITER7

n 4444 4159 20,536 6595 6605 9014 Secondary High Risk Primary Patients Experiencing Major CHD Events, % Placebo Statin 19.4 12.3 10.2 8.7 5.5 6.8 28.0 15.9 13.2 11.8 7.9 10.9 CHD events occur in patients treated with statins 1.4 0.8 17,802

On‐treatment LDL‐C (mg/dL) 55 115 140 93 97 112 117

5Shepherd J et al. N Engl J Med. 1995;333:1301-1307. 6 Downs JR et al. JAMA. 1998;279:1615-1622. 7 Ridker PM et al. N Engl J Med. 2008;359:2195-2207. 14S Group. Lancet. 1994;344:1383-1389. 2LIPID Study Group. N Engl J Med. 1998;339:1349-1357. 3Sacks FM et al. N Engl J Med. 1996;335:1001-1009. 4HPS Collaborative Group. Lancet. 2002;360:7-22.

: Only 23% ‐ 43% risk reduction across all studies

Change in LDL-C

• n Statin and MACE Event Rates

Ridker PM et al. Eur Heart J. 2016. doi:10.1093/eurheartj/ehw046. ‐70 80 ‐90

Change in LDL‐C (%) (High Intensity Statin)

10 50 ‐30

Individual Observations (N=7856)

4800 1200 7200 ‐80 70 ‐10 30 ‐50 40 ‐40 60 ‐20 20 ‐60 2400 6000 3600

Placebo No Reduction/Increase <50% Reduction ≥50% Reduction

12

MACE Event Rate / 1000 Person‐Years

6 10 2 4 8 5 9 1 11 3 7 11.2 9.2 6.7 4.8

Greatest risk

Statin-Treated CHD Patients Achieving LDL-C < 1 0 0 m g/ dL and < 7 0 m g/ dL

Jones PH et al. J Am Heart Assoc. 2012; doi 10.1161/JAHA.112.001800. Administrative Claims Data 2003‐Sept 2010 Electronic Medical Records 2003‐Sept 2010

• Ntl. Health & Nutrition Exam. Survey 2007‐2008

80

Patients (%)

60 70 40 20

As Percent of All Treated Patients

10 50 30

As Percent of All Treated High‐Risk Patients As Percent of All Treated CHD Patients

49.3 High‐Risk Patients 51.4 24.8 CHD Patients 22.1 37.9 CHD Patients at LDL‐C Goal (<100 mg/dL) 30.5 14.3 CHD Patients at LDL‐C Goal (<70 mg/dL) 13.2 75.5 CHD Patients at LDL‐C Goal (<100 mg/dL) 71.0 28.4 CHD Patients at LDL‐C Goal (<70 mg/dL) 30.9 43.6 19.0 30.5 10.3 70.1 23.7

Statin I ntolerance and Risk of Coronary Events

Cumulative Incidence for Recurrent MI, CHD Events, and All-Cause Mortality

Serban MC et al. J Am Coll Cardiol. 2017;69:1386-1395.

A Study of 105,329 Medicare beneficiaries who began a moderate‐ or high‐intensity statin dosage after hospitalization for MI

Adverse Impacts of Severe ASCVD Is PCSK9 Inhibition the Key to Improving Patient Outcomes?

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Disease Trajectories and CVD Risk Reduction

Packard CJ et al. Vasc Pharmacol. 2015;71:37‐39.

Non-Statin LDL-Low ering Therapies: Ezetim ibe

Ezetim ibe: I MPROVE I T Trial Design

• Cannon CP et al. Am Heart J. 2008;156:826-832.

Study drug is administered once daily in the evening.

Patients stabilized post‐ACS ≤10 days LDL‐C ≤125 mg/dL (or ≤100 mg/dL if prior statin)

Double‐blind n ~ 18,000 ASA + Standard Medical Therapy Simvastatin 40 mg* Ezetimibe/ Simvastatin 10/40 mg* Follow‐up visit day 30, every 4 months Duration: Minimum 2.5 year follow‐up (5250 events) Primary Endpoint: CV death, MI, Hospitalization for UA, Revascularization (>30 days after randomization), or Stroke *up‐titrated to 80 mg if LDL‐C >79 mg/dL

Cannon CP et al. Am Heart J. 2008;156:826-832.

I MPROVE I T Trial: Effect on LDL-C

Ezetimibe (EZ) + Simvastatin vs Simvastatin Alone

Study drug is administered once daily in the evening.

100 90 80 70 60 50 40 QE R 1 4 8 12 16 24 36 48 60 72 84 96 Time since randomization (months) EZ/Simvastatin 53.2 125.8 120.4 48.7 3.3 Mean LDL‐C (mg/dL) Simvastatin 69.9 145.1 137.1 48.1 3.8 Δ in mg/dL ‐16.7 ‐19.3 ‐16.7 +0.6 ‐0.5 1 yr mean LDL‐C TC TG HDL‐C hs‐CRP Simvastatin EZ/Simvastatin

Cannon CP et al. N Engl J Med. 2015;371:2387-2397.

I MPROVE I T Trial: Ezetim ibe + Sim vastatin vs Sim vastatin Alone

7 6 5 4 3 2 1 10 20 30 40 Time Since Randomization (years) Primary Endpoint Event Rate (%) Ezetimibe/Simvastatin – 32.7% 2572 events Simvastatin – 34.7% 2742 events NNT = 50 HR 0.936 CI (0.887, 0.988) P=0.016

7‐year event rates

I MPROVE-I T: Ezetim ibe vs Statin Benefit – Change in LDL-C vs Clinical Benefit

Cannon CP et al. CTT Collaboration. Lancet. 2005;366:1267-1278. CCT Collaboration. Lancet. 2010;376:1670-1681. Cannon CP et al. N Engl J Med. 2015;372:2387-2397.

Reduction in Rate of Major Vascular Events (%) Reduction in LDL Cholesterol: mmol/L (mg/dL)

2.0 (77.2) 1.5 (57.9) 1.0 (38.6) 0.5 (19.3)

Adverse Impacts of Severe ASCVD Is PCSK9 Inhibition the Key to Improving Patient Outcomes?

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Non-Statin LDL-Low ering Therapies: PCSK9 I nhibitors

Sever P, Mackay J. Br J Cardiol. 2014;21:91-93 Giugliano RP et al. Lancet. 2012;380:2007-2017 Sabatine MS et al. N Engl J Med. 2015;372:1500-1509

• Chaperones LDL-R to destruction   circulating LDL-C
• Loss-of-fxn genetic variants   LDL-R   LDL-C &  risk of MI

PCSK9 Physiology: Proprotein Convertase Subtilisin/ Kexin Type 9 ( PCSK9 )

evolocuma b

PCSK9 Loss-of-Function Mutations: Low er LDL-C Levels and Reduced CHD Rates

• Wild-type PCSK9 degrades LDL

receptors.1,2

• Loss-of-function (LOF) mutations

increase hepatic LDL receptor expression, reducing LDL-C levels by 15%-40%.2,3

• CHD incidence was reduced

47%-88% in PCSK9 loss-of- function mutation carriers compared with normal individuals.3

• 1. Peterson AS et al. J Lipid Res. 2008;49:1595-1599.
• 2. Cohen J et al. Nature Genetics. 2005;37:161-165.
• 3. Cohen JC et al. N Engl J Med. 2006;354:1264-1272.

n=301 n=9223

11.8 6.3

Black Subjects

12

CHD (%)

2 8 10 6

White Subjects

Normal Subject Mutation Carrier n=85 n=3278

9.7 1.2

4

P=.008 P=.008

Week

3.1 mmol/L 118.9 mg/dL 1.3 mmol/L 48.3 mg/dL 3.2 mmol/L 123.0 mg/dL 1.4 mmol/L 53.1 mg/dL

mg/dL Placebo Alirocumab LDL-C, LS mean (SE), mmol/L Achieved LDL-C Over Time All patients on background of maximally-tolerated statin ±other lipid-lowering therapy

Alirocumab 150 mg Q2W

Alirocum ab: ODYSSEY Long-Term

Stable LDL-C Reduction

Robinson J et al. ESC hotline session; Barcelona; Aug 31, 2014.

Alirocum ab: Post hoc Analysis – Major Adverse Cardiovascular Events*

Placebo + maximally tolerated statin ± other LLT Alirocumab + maximally tolerated statin ± other LLT Cumulative Probability of Event Time (weeks)

Cox model analysis HR = 0.52 (95% CI 0.31 to 0.90) Nominal P-value = 0.02

• No. at risk:

Placebo Alirocumab 788 776 731 700 670 653 644 597 1550 1533 1445 1392 1342 1306 12661170 1.0 0.8 0.6 0.4 0.2 0.0 12 24 36 52 64 78 86 0.06 0.04 0.02 0.00 12 24 36 52 64 7886 Robinson JG et al. N Eng J Med. 2015;372:1489-1499. *Based on primary endpoint for the ODYSSEY Long-Term trial, including CHD death, non-fatal MI, fatal and non-fatal ischemic stroke, and unstable angina requiring hospitalization. Unstable angina requiring hospitalization was considered based on strict criteria/clear progression of ischemia.

Alirocum ab: ODYSSEY Long-Term

MACE Rate by Average LDL- C During Treatm ent Period

75 100 125 150 Average LDL-C during the treatment period (mg/dL) Adjusted rate of MACE (per 100 patient years) 25 0.5 1.0 1.5 2.0 2.5 3.0 50 Event rate 95% CI HR 0.76 (0.63 to 0.91) per 39 mg/dL decrease (P=0.0025)

Multivariate analysis adjusted on baseline characteristics; pool of Phase 3 trials

Adverse Impacts of Severe ASCVD Is PCSK9 Inhibition the Key to Improving Patient Outcomes?

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Evolocum ab: The GLAGOV Trial

Nicholls SJ et a. JAMA. 2016;316:2373-2384.

Progression of Coronary Atherosclerosis on Statin +/- Evolocumab

420 mg (sc) weekly

Effect of Evolocum ab on Progression of Coronary Artery Disease in Statin- treated Patients

Nicholls SJ et a. JAMA. 2016;316:2373-2384.

Post Hoc Analysis Examining the Relationship Between Achieved LDL-C Level and Change in Percent Atheroma Volume Local regression (LOESS) curve illustrating the post hoc analysis of the association (with 95% confidence intervals) between achieved low- density lipoprotein cholesterol (LDL-C) levels and the change in percent atheroma volume in all patients undergoing serial IVUS evaluation. Curve truncated at 20 and 110 mg/dL owing to the small number of values outside that range.

The GLAGOV Randomized Double-Blind Clinical Trial

Random ized Open-Label Extension of OSLER-1 & OSLER- 2 ( RDBCTs) : Evolocum ab vs Placebo on MACE

Open label study of 4465 pts randomized to evolocumab 140 mg SC Q2W

• r 420 mg SC QM + standard of care (SOC) or SOC for 48 wks

CV Events

• Death
• MI
• UA requiring

hospitalization

• CVA
• TIA
• Hosp w CHF

Kaplan-Myer estimates at 1 yr Hazard ratio, 0.47; 95% CI, 0.28-0.78 p=0.003 CV Events SOC = 2.18% Evolocumab = 0.95%

Sabatine MS et al. N Engl J Med. 2015;372:1500-1509.

Evolocum ab: FOURI ER Trial Design

Evolocumab SC 140 mg Q2W or 420 mg QM Placebo SC Q2W or QM LDL-C ≥70 mg/dL or non-HDL-C ≥100 mg/dL Follow-up Q 12 wks (over 2.2 y median f/u) Screening, Lipid Stabilization, and Placebo Run-in High or moderate intensity statin therapy (± ezetimibe) 27,564 high-risk, stable patients with established CV disease (prior MI, prior stroke, or symptomatic PAD)

RANDOMIZED DOUBLE BLIND

Sabatine MS et al. Am Heart J. 2016;173:94-101.

Evolocum ab: FOURI ER– LDL Cholesterol

Sabatine MS et al. Am Heart J. 2016;173:94-101.

Evolocum ab: FOURI ER– Prim ary Efficacy Endpoint

Sabatine MS et al. Am Heart J. 2016;173:94-101.

Adverse Impacts of Severe ASCVD Is PCSK9 Inhibition the Key to Improving Patient Outcomes?

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Evolocum ab: FOURI ER– Landm ark Analysis

Sabatine MS et al. Am Heart J 2016;173:94-101. Sabatine MS et al. Am Heart J. 2016;173:94-101.

PCSK9 I nhibition: LDL-C Low ering Efficacy in Long-term Studies

• Osler1: Open label study of 4465 pts randomized to evolocumab 140 mg SC Q2W or

420 mg SC QM + standard of care (SOC) vs SOC for 48 weeks

• Odyssey Long Term2: Blinded study of 2341 high risk pts on max-tolerated statin with

LDL-C > 70 randomized to alirocumab 150 mg or placebo SC Q2W for 78 wks Patients % LDL-C ∆ At 12/24 wks % LDL-C ∆ At 48/72 wks Evolocumab 140 mg SC Q2W or 420 mg SC QM1 (baseline LDL-C = 120 mg/dL)

• 61% (P<0.001)*
• 61% (P<0.001)

Alirocumab 150 mg SC Q2W2 (baseline LDL-C = 123 mg/dL)

• 62% (P<0.001)ƚ
• 56% (P<0.001)

*Proportion of patients with LDL-C < 70 mg/dL = 74% ƚ Proportion of patients with LDL-C < 70 mg/dL = 79%

• 1. Sabatine et al. N Engl J Med. 2015; 372:1500-1509. 2. Robinson et al. N Engl J Med. 2015;372:1489-1499.

2 0 1 6 ESC/ EAS Guidelines on Dyslipidem ias: Pharm acological Treatm ent of Hypercholesterolem ia

Catapano AL. Euro Heart J. 2016;37:2999-3058. Class of Recommendation: I = strong IIa = moderate IIb = weak Level of Evidence: A = strong B = moderate C = limited

Patient Populations Addressed: 4 Groups Benefiting from Lipid Low ering

Lloyd-Jones DM et al. J Am Coll Cardiol. 2016:68:92-125. Lloyd‐Jones D et al. J Am Coll Cardiol. 2016;68:92‐125.

2 0 1 6 ACC/ AHA Expert Consensus Decision Pathw ay

Lloyd-Jones DM et al. J Am Coll Cardiol. 2016:68:92-125.

Determ ining W hen to Add Nonstatin Therapy

Adverse Impacts of Severe ASCVD Is PCSK9 Inhibition the Key to Improving Patient Outcomes?

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LDL-C Response Variability to High- I ntensity Statin Therapy and I m plications for the Allocation of PCSK9 I nhibitors

Ridker PM et al. Eur Heart J. 2016. doi:10.1093/eurheartj/ehw046. ‐70 80 ‐90

Change in LDL‐C (%) (High Intensity Statin)

10 50 ‐30

Individual Observations (N=7856)

4800 1200 7200 ‐80 70 ‐10 30 ‐50 40 ‐40 60 ‐20 20 ‐60 2400 6000 3600 PCSK9 Inhibitor Greatest Theoretical Benefit PCSK9 Inhibitor Least Theoretical Benefit PCSK9 Inhibitor Intermediate Theoretical Benefit N=2734 (34.8%) N=1573 (20.0%) N=3549 (45.2%)

No Reduction/ Increase in LDL‐C <40% Reduction in LDL‐C 40‐60% Reduction in LDL‐C >60% Reduction in LDL‐C

The Gap Betw een W hat W e Know and W hat W e Do

“Drugs don’t work in patients who don’t take them.”

– C. Everett Koop

Former US Surgeon General

Barriers to Medication Adherence

Adherence Toolkit. https://www.lipid.org/sites/default/files/adherence_toolkit.pdf.

Benefits of Shared Decision-m aking

• Learn about their health
• Recognize a decision is necessary
• Understand pros and cons
• Have the information and tools needed to evaluate
• Are better prepared to talk
• Collaborate with their healthcare team
• Are more likely to follow through with the decision
• Builds a lasting and trusting relationship

https://www.healthit.gov/sites/default/files/nlc_shared_decision_making_fact_sheet.pdf. Cannon CP et al. JAMA Cardiol. doi:10.1001/jamacardio.2017.2289. Published online August 2, 2017.

Sim ulation of Lipid-Low ering Therapy I ntensification in ASCVD

• Large gaps exist between recommendations and

current practice

• Model assumes no lipid lowering therapy (LLT)

intolerance and full adherence

• Intensification of oral LLT could achieve an LDL-C

level of less than 70mg/dL in most patients, with only a modest percentage requiring a PCSK9 inhibitor.

Adverse Impacts of Severe ASCVD Is PCSK9 Inhibition the Key to Improving Patient Outcomes?

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• In a contemporary US

population with ASCVD,

• nly 53.2% received a

statin at baseline

• Only 15.3% received a

high-intensity statin

• This treatment 25.2%

achieving LDL-C levels of less than 70mg/dL

Cannon CP et al. JAMA Cardiol. doi:10.1001/jamacardio.2017.2289. Published online August 2, 2017.

Sim ulation of Lipid-Low ering Therapy I ntensification in ASCVD

JAMA Cardiol. doi:10.1001/jamacardio.2017.2289. Published online August 2, 2017.

Logic of Lipid-Low ering Treatm ent I ntensification and Proportion of Patients Flow ing Through the Treatm ent I ntensification Logic in the Sim ulation

I nterventions to I m prove Adherence

Adherence Toolkit. https://www.lipid.org/sites/default/files/adherence_toolkit.pdf.

Conclusions

• People with life-time low LDL-C are at low risk for ASCVD; those with high LDL-

C have increased risk

• Despite significant reduction in LDL-C and CVD risk associated with statin use,

considerable residual risk persists.

• High-risk patients remain untreated to LDL goals for many reasons, including

statin intolerance

• The addition of ezetimibe to statins yields incremental but modest improvements

in CVD risk.

• PCSK9 inhibitors represent the most promising new class of LDL-C lowering

therapy and ongoing outcomes trials will help to determine the clinical utility of these agents.

• Lipid-lowering therapies improve outcomes of patients with ASCVD, but to be

effective, they must be taken as prescribed.

Thank you!