PCSK9 INHIBITORS FOR THEINTERVENTIONALIST:WHICH

PATIENTS DO WE CHOOSE ANDHOW DO WE USE?HOW DO WE USE?Douglas W Triffon, MD, FACC, FNLA

Medical Director of the Lipid Disorders Clinic

Scripps Clinic and Research Foundation

Commercial Interest

Nature of Relevant Financial Relationship

(Include all those that apply)

What was received For what role

Self Spouse/Partner

Janssen

AmarinHonorarium Speaker X

Regeneron/Sanofi Honorarium Speaker X

AmgenHonorarium

Speaker X

RISK OF RECURRENT EVENTS

• Research to date has shown significant heterogeneity in theestimated 10-year risk in patients with previous cardiovasculardisease ranging from less than 10% to over 50% risk of recurrentvascular events.

• A single one size fits all approach to secondary prevention isinappropriate. The identification of extreme high risk patients usingrisk stratification tools will prompt the initiation of more intensivetreatments in order to reduce high residual risk.

Circulation:Nov 8, 2016;134(19):1441-1443

EXTREME HIGH RISK

Source # Major CVEvents

Total #Participants

4S, 1998 510 2072

AFCAPS, 1998 92 2868

LIPID, 1998 1288 4185

CARDS, 2004 50 1282

TNT, 2005 1763 9400

IDEAL, 2005 1294 8396

SPARCL, 2006 308 2118

JUPITER, 2008 82 7832

OVERALL 5387 38153

Boekholdt SM, Arsenault BJ, Mora S, Terje R. Pedersen, LaRosa JC, Nestel PJ, Simes RJ,Durrington P, Hitman GA, Welch KMA, DeMicco DA, Zwinderman AH, Clearfield MB,

Downs JR, Tonkin AM, Colhoun HM, Gotto Jr AM, Ridker PM, Kastelein JJP.JAMA. 2012;307(12):1302-1309

7.3

14.2

17.117.9

10

15

20

Mean LDL-C Achieved Quartiles & Major CV Events

Lipid and Apolipoprotein Levels and Risk of MajorCardiovascular Events in Statin-Treated Patients

Major CVEventRate, %,in Statin-TreatedPatientsa

Lowest ASCVD risk= LDL-C goal of

<62 mg/dL(mean 49 mg/dL)

7.3

0

5

49 74 97 129

Range, mg/dL <62 62-85 86-108 >109

Events / Total 697 / 9538 1360 / 9573 1616 / 9478 1714 / 9564

Boekholdt SM, Arsenault BJ, Mora S, Association of LDL Cholesterol, Non–HDLCholesterol, and Apolipoprotein B Levels With Risk of Cardiovascular Events AmongPatients Treated With Statins: A Meta-analysis. JAMA. 2012;307(12):1302-1309

Mean LDL-C, mg/dL

LOWER IS BETTER

60% LDL-C LOWERING FROM PCSK9 INHIBITOR

10 yr RISK ABSOLUTE RISK REDUCTION

5 1.2 1.6 1.97 2.31 2.6

7.5 1.78 2.4 2.96 3.46 3.9

10 2.4 3.2 3.95 4.61 5.2

20 4.7 6.3 7.89 9.23 10

30 7 9.6 11.84 13.84 15.59

50 12 16 19.7 23 26

Baseline LDL-C 70 100 130 160 190

60% LDL-C LOWERING FROM PCSK9 INHIBITOR

10 yr RISK NNT

5 84 62.5 50.76 43 38

7.5 56 41.7 33.78 28.9 25.6

10 42 31 25.3 21.69 19

20 21 15.6 12.67 10.83 9.62

30 14 10 8.45 7.23 6.41

50 8 6.2 5 4.3 3.85

Baseline LDL-C 70 100 130 160 190

Hs-CRP and CV Events in the Fourier Trial

Lp(a) and the Fourier Trial

Median Lp(a) =37 nmol/L

Fourier Trial and PAD

PCSK9 Inhibitors and Prior MI

Circulation. 2018;138:756–766. DOI: 10.1161/CIRCULATIONAHA.118.034309

Median time from MI =0.6 yrs vs 6 yrs

PCSK9 INHIBITORS AND MULTIVESSEL DISEASE

Circulation. 2018;138:756–766. DOI: 10.1161/CIRCULATIONAHA.118.034309

ODYSSEY OUTCOMES TRIAL

11.10%

16.40%

14.10%

12.00%

14.00%

16.00%

18.00%

ODYSSEY OUTCOMES TRIAL

ARR=2.3%

ARR=1.6%11.10%

9.50%

0.00%

2.00%

4.00%

6.00%

8.00%

10.00%

12.00%

Non DiabeticPlacebo

Non Diabetic Rx DiabeticPlacebo

Diabetic Rx

ADA Meeting June, 2018

SUMMARY• The majority of patients under the care of cardiologists are extreme

high risk for future cardiac events.

• This risk is largely unrecognized and undertreated.

• Residual risk is 5 times more important than residual high LDL-C in• Residual risk is 5 times more important than residual high LDL-C inpredicting the benefit of aggressive cholesterol therapy postintervention.

• Higher risk translates into higher benefits of aggressive treatment.

• Recognize the risk, calculate the risk, target the risk, and treat the riskmore aggressively.