presentation: lipoprotein (a) and pcsk9 drug inhibitors ...of minnesota. to help focus his career in...

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C A R D I O L O G Y G R A N D R O U N D S Presentation: Prevention Case Carousel: The New Risk Calculator,

Lipoprotein (a) and PCSK9 Drug Inhibitors: How do they fit in clinical practice?

Date: Monday, March 2, 2015, 7:00 – 8:00 AM Moderator:

Speakers:

Thomas Knickelbine, MD, FACC, FSCAI, FSCCT - Director, Preventive Cardiology Minneapolis Heart Institute® at Abbott Northwestern Hospital Dr. Thomas Knickelbine has been with the Minneapolis Heart Institute since 1996 actively practicing cardiology. He co-founded Minnesota Heartscan in 1999 with Dr. Robert Van Tassel and helped pioneer the initial calcium scoring program in the state of Minnesota. He has been active in preventative cardiology for the past ten years. He is a fellow of the American College of Cardiology, Society of Cardiovascular CT, and Society of Cardiac Angiography and Interventions. He is interested in advanced preventive techniques including NMR particle sizing and calcium scoring in intermediate risk patients. He is also interested in the use of the electronic medical record in Primary Prevention protocols and pathways development. Dr. Knickelbine has published more than 30 manuscripts and abstracts.

Terrence Longe, MD, FACC, FSCCT - Consulting Cardiologist Minneapolis Heart Institute® at Abbott Northwestern Hospital Received Bachelors Science degree at University of Michigan, M.D. at Wayne State University, Residency at Wm Beaumont Hospital in Michigan, and Cardiology Fellowship at Northwestern University in Chicago. Practicing as a Consulting Cardiologist with Minneapolis Heart institute since 1987. Participating in Clinical services and Prevention, as well as Cross-Sectional Imaging in Cardiac CT, Cardiac MRI, and Echo.

Michael D. Miedema, MD, MPH - Cardiologist Minneapolis Heart Institute® at Abbott Northwestern Hospital Dr. Michael D Miedema is cardiologist with the Minneapolis Heart Institute with a focus on cardiovascular prevention. Dr. Miedema obtained his medical degree from the University of Minnesota and subsequently completed an internal medicine residency at Abbott Northwestern Hospital. He went on to complete a cardiovascular fellowship at the University of Minnesota. To help focus his career in cardiovascular prevention, he then obtained a Master's of Public Health from the Harvard University School of Public Health while participating in a cardiovascular prevention fellowship at Brigham and Women's Hospital in Boston, Massachusetts. Dr. Miedema started his position with MHI in August of 2013. Twenty-five percent of his time will be spent with the Minneapolis Heart Institute Foundation working on preventive cardiovascular research.

Location: ANW Education Building, Watson Room

OBJECTIVES 1. Describe new treatment guidelines. 2. Explain Lp(a)'s potential for improved risk discrimination 3. Analyze how to refer a patient for consideration of a clinical trial in PCSK9 inhibition.

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ACCREDITATION Physicians: This activity has been planned and implemented in accordance with the Essential Areas and policies of the Accreditation Council for Continuing Medical Education (ACCME) through the joint sponsorship of Allina Health and Minneapolis Heart Institute Foundation. Allina Health is accredited by the ACCME to provide continuing medical education for physicians.

Allina Health designates this live activity for a maximum of 1.0 AMA PRA Category 1 Credit(s)TM. Physicians should only claim credit commensurate with the extent of their participation in the activity.

Nurses: This activity has been designed to meet the Minnesota Board of Nursing continuing education requirements for 1.2 hours of credit. However, the nurse is responsible for determining whether this activity meets the requirements for acceptable continuing education.

Others: Individuals representing other professional disciplines may submit course materials to their respective professional associations for 1.0 hours of continuing education credit.

DISCLOSURE STATEMENTS Speaker(s): All faculty have declared that they do not have any conflicts of interest in making this presentation.

Planning Committee: Dr. Michael Miedema, and Eva Zewdie have declared that they do not have any conflicts of interest associated with the planning of this activity. Dr. Robert Schwartz declared the following relationships - stockholder: Cardiomind, Interface Biologics, Aritech, DSI/Transoma, InstyMeds, Intervalve, Medtronic, Osprey Medical, Stout Medical, Tricardia LLC, CoAptus Inc, Augustine Biomedical; scientific advisory board: Abbott Laboratories, Boston Scientific, MEDRAD Inc, Thomas, McNerney & Partners, Cardiomind, Interface Biologics; options: BackBeat Medical, BioHeart, CHF Solutions; speakers bureau: Vital Images; consultant: Edwards LifeSciences.

Cardiovascular Grand Rounds 2‐Mar‐2015Minneapolis Heart Institute® at Abbott Northwestern Hospital Page 1

Case: Cholesterol Elevation

Post ACS

MHI Grand Rounds 2015

Thomas Knickelbine, MD

Director: Preventive Cardiology

Minneapolis Heart Institute

Minneapolis MN

Suboptimal Rx in ASCVD• 60 Yo female referred to Lipid Clinic for evaluation

of persistent hyperlipidemia

• 9 months prior ACS (NSTEMI) with PCI of LAD, mild/mod RCA and LCx disease present

• LDL at that time 162, initiated on Zocor

• Medications: Crestor 5 mg – (intolerant to other statins, zetia and higher doses)

•Current Total cholesterol: 230 mg/dl

Triglycerides: 160 mg/dlHDL cholesterol: 50 mg/dlLDL cholesterol: 148 mg/dl


Hyperlipidemia: New Guidelines

STATIN INTOLERANCEComplete or Partial

Loss of Function Mutations of PCSK9

Cohen JC et al. N Engl J Med 2006;354:1264-1272.

28 percent reduction in mean LDL cholesterol 88% reduction in CV events in the ARIC database


PCSK9 Inhibitors

• Amgen: Evolocumab• Regeneron/Sanofi: Alirocumab• Pfizer: Bococizumab

• Injectable Monoclonal Antibodies to PCSK9


ODYSSEY LONG TERM TRIAL: ESC 20142431 pt (aged approximately 65 years)High cholesteroland high risk or FH


DESCARTES: Other Lipids at Week 52

0

6%

-2

0

2

4

6

3%(-17 to 25)

-9%(-26 to 13)

2%ApoB

Lp(a)

HDL-C

ApoA1

Triglycerides

-42%-50

-40

-30

-20

-10

0

10

-1%

2%

-2

-1

0

1

2

3-6%

(-21 to 1)

-28%(-49 to -6)

-30

-25

-20

-15

-10

-5

0

Placebo QM

Evolocumab 420 mg QM

Perc

ent

Chan

ge f

rom

Bas

elin

e, M

ean (

%)

Perc

ent

Chan

ge f

rom

Bas

elin

e, M

edia

n (

%)

Perc

ent

Chan

ge f

rom

Bas

elin

e, M

edia

n (

%)

Perc

ent

Chan

ge f

rom

Bas

elin

e, M

ean (

%)

Perc

ent

Chan

ge f

rom

Bas

elin

e, M

ean (

%)

-6-4-20246

-10-8 Error bars represent standard error

Data in parentheses represent Q1 to Q3


Potential Candidates for PCSK9 Clinical Trials at MHIF

• ACS within past year and suboptimal treated– LDL > 70 or Apo B > 80 or Non HDL > 100– Max tolerated treatment or statin intolerant– Odyssey outcomes trial (18 K, 64 months) with

Alirocumab

• Pts with documented CVD or High CV risk without CVD– DM, Abnormal ABI, CKD (GfR < 60), FH, LDL > 190 ,

Lp(a), smoker, low HDL < 40, elevated hs CRP– “SPIRE” Trials with Bococizumab

HDL

• Renewed interest in HDL• Cholesterol efflux capacity critical


HDL-C ≠ CHD

0%

5%

10%

15%

20%

25%

0 1 2 3 4Years

Niaspan

Placebo

CETPI AIM-HIGH

HPS2

DalcetrapibTorcetrapib

Drug Class TrialHDL-C change

NIACINAIM-HIGH 25%

HPS2-THRIVE

15%

CETPITorcetrapib 72%

Dalcetrapib 35%

Boden WE, et al. NEJM 2011;365:2255-67

Barter PJ, et al. NEJM 2007;357:2109-22

Schwartz GG, et al. NEJM 2012;367:2089-99

HPS2-THRIVE. NEJM 2014;371:203-12

In RCTs

ASCVD Events According to Models Based on HDL Cholesterol Level and Cholesterol Efflux Capacity

HDL cholesterolUnadjusted analysis 0.64 (0.40-1.03)

Analysis adjusted

For traditional risk factors 0.80 (0.47–1.37)

For traditional risk factors and HDL particle concentration

1.08 (0.59–1.99)

Cholesterol efflux capacityUnadjusted analysis 0.44 (0.27–0.73)

Analysis adjusted

For traditional risk factors 0.30 (0.18–0.50)

For traditional risk factors and HDL cholesterol

0.31 (0.18–0.52)

For traditional risk factors and HDL particle concentration

0.34 (0.20–0.56)

For traditional risk factors, HDL cholesterol, and HDL particle concentration

0.33 (0.19–0.55)

Rohatgi et al., NEJM (2014)


HDL Function: Reverse Cholesterol Transport

Rader DJ, Hovingh GK. Lancet 2014;384:618-625

apoA-I

apoA-I

apoA-I

ABCA1

ABCA1

ABCG1

SRB1

VLDL

Adorni MP, et al. J Lipid Res 2007;48:2453-62

Macrophage

Liver

Bile/Feces

Khera AV, et al. NEJM 2011;364:127-35

presentation: lipoprotein (a) and pcsk9 drug inhibitors ...of minnesota. to help focus his career in...

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