Niacin Presentation

7/29/2019 Niacin Presentation

http://slidepdf.com/reader/full/niacin-presentation 1/41

New Treatments of

Hypercholesterolemia

Jason A. Logan

Family Medicine Clerkship Presentation

4/27/01



Introduction

Hypercholesterolemia- Why do we Care?1. Affects 65 Million U.S. Adults

2. Independent Risk Factor for CHD

3. CHD #1 Killer in U.S.

4. My fianceé has it

>200 mg/dl Total Cholesterol

LDL>130 HDL<40 mg/dl



Don’t We Already Have it

Figured Out?

1. ONLY worry about LDL

2. If LDL is high- Put ALL PatientsONLY on a Statin for life

3. Pat yourself on the back when LDLis decreased and forget about your

patients who die of heart attacks

despite being on a statin



Men’s Health, June 2001



Men’s Health, June 2001

“He hasn’t been trained in the latesttechnology.”

“He isn’t aware of the latest treatment.”

“The test that he relies on will miss 8 outof 10 cases.”

“Yet the enemy he is fighting is heart

disease, the leading killer of men.” “Who is he?”

“He’s your doctor.”



NCEP Guidelines for Lipid Management1

Definite

AtheroscleroticDisease*

Two or more

Other RiskFactors**

LDL-Cholesterol mg/dL, (mmol/L)

Initiation Level Minimum Goal

No No > 190

(> 4.9)

< 160

(< 4.1)

No Yes > 160

(> 4.1)

< 130

(<3.4)

Yes Yes or No > 130

(> 3.4)

< 100

(<2.6)

*Coronary heart disease or peripheral vascular disease (including symptomatic carotid artery

disease).

** Other risk factors for coronary heart disease (CHD) include: age (males > 45 years, females > 55years or premature menopause without estrogen replacement therapy); family history of premature

CHD; current cigarette smoking; hypertension, confirmed HDL-C < 35 mg/dL (< 0.91 mmol/L); and

diabetes mellitus. Subtract 1 risk factor if HDL-C is > 60 mg/dL (> 1.6 mmol/L).



LDL Cholesterol – Primary Target of Therapy

1. <100 Optimal

2. 100-129 Near optimal/above optimal

3. 130-159 Borderline high

4. 160-189 High

5. >190 Very high

ATP III Classification ofLDL, Total, and HDL Cholesterol

(JAMA- May 16, 2001)



Total Cholesterol

<200 Desirable200-239 Borderline high

>240 High

HDL Cholesterol

<40 Low

>60 High



Impact of ATP III

number of patients that should be oncholesterol-lowering medication by 300%

from 12 million to 36 million

Threshold for HDL to 40 mg/dl (from 35)

Threshold for Elevated Triglycerides

Risk factor status of Diabetics to equal

that of someone with CHD



Impact of ATP III (cont)

New Treatment Category:

Metabolic syndrome=

Obesity, HTN, Glc, TGs, HDL

Recommended initial test=

Complete lipid panel

Total cholesterol, LDL, HDL, and TGs

Combination therapy highlighted-

Statin +Niacin, and Statin + BAS



Current Treatment Methods

1. Exercise and Diet

2. HMG- CoA Reductase Inhibitors

(Statins)

New Treatment Methods

1. Niacin

2. Niacin + Statin



Current Treatment Methods

1. Exercise and Dieta. Poor compliance

b. Usually cannot get to target levels

2. Statins

a. Great at lowering LDL levels

b. Not much affect on Lipoprotein(a), HDL,or small dense LDL, and minor effects on

Triglycerides



Who Cares?

The National Cholesterol EducationalPanel (NCEP) Cares and in 1993-Began focusing more on other major

lipids in addition to LDL1

This In-Depth Study Revealed aPlethora of Information related to CHDRisk



Lipid Parameter Function:

Latest Commentary1

VLDL

Carries triglycerides to peripheral cells

High levels may be associated with increased CHD risk2

LDL

Carries cholesterol to cells

High levels linked to increased CHD risk

Primary target of cholesterol-reducing therapy3

HDLRemoves cholesterol from cells

High HDL considered protective against CHD

HDL >60 mg/dL decreases CHD risk1

Lipoprotein(a)

A complex of LDL and apolipoprotein(a)Prevents LDL from being taken up by the Liver

Elevated Lp(a) is an independent risk factor for premature CHD4

Triglycerides

A neutral fat stored in adipose cells

Positively correlated with risk for CHD1



Your Patients Care Too, Because:

25% of Men with a FH of CHD:

1st Sign of Heart Disease is SuddenDeath

50% of arteriosclerosis can’t beexplained by standard risk factors(smoking, diet, lifestyle, and highcholesterol)

80% of people who develop CHD havethe same basic cholesterol numbers as

those who don’t have CHD



New Lab Technology

Berkeley Heart Lab and Lipoprofile

LDL sub-classes- small dense (IIIa andIIIb) vs large buoyant

HDL sub-classes- HDL2b

Lp(a)

Homocysteine

Insulin

C-reactive protein



HDL

Has been shown to be Cardioprotective in theFramingham Heart Study, and inretrospective analyses of intervention trialssuch as the Coronary Primary Prevention

Trial and the Multiple Risk Factor InterventionTrial 5-7

The data were consistent with a 2% to 3%

decrease in CHD risk for each 1 mg/dLincrease in HDL, after adjustment to controlfor other risk factors.



VA- HIT Study on HDL8

The importance of raising HDL to reduce morbidity and mortality

was clearly confirmed with the publication August 1999 in the NEJM of the findings of the landmark Veterans Administration High Density

Lipoprotein Intervention Trial (VA-HIT) clinical outcome study.



Niacin (9, 10, 11)

Increases HDL by up to 26%

Decreases LDL by up to 17%

Decreases TGs by up to 35%

Decreases Lp(a) by up to 27%



The Uniqueness of Niacin

Increases HDL better than ANY other medication and increases HDL2b themost

Only drug that has been shown toswitch subclasses of LDL from smalldense (IIIa and IIIb), to large buoyant

(Pattern B to Pattern A)

Decreases Lp (a) the best of any

medication



Why Isn’t Everyone on Niacin!?!

Main Reason- Flushing

Difficult Dosing (TID)

It’s too cheap (No $$$ for Drug

companies)



Solution: Niaspan®: A New

Extended Release Form of Niacin

Niaspan® is the Only Once-Daily ClinicallyTested Niacin Product Approved by the FDAfor the Treatment of Cholesterol and LipidDisorders

HydroGel Programmed-Release™ formulation

Minimizes flushing Once-at-Night™ dosing

Mean liver enzyme levels remain within normallimits9,10,11



Decreased Flushing

1. Niaspan®

has been shown todecrease flushing episodes by 78% vs

Immediate-Release Niacin10



Flushing Tips

When beginning or increasing dose- take

400mg Ibuprofen (or equivilant Naproxen or Aspirin) 30 min before Niaspan®

Avoid Hot drinks, Hot shower, or spicy foods

1 hr before or anytime after Niaspan® dosing

Eat a low-fat snack with Niaspan®

Take right before going to bed



Niaspan® (Continued)

2. Easy Once a Day Dosing at Bedtime(Most Free Fatty Acid Mobilization OccursNocturnally)

3. Minimal to No Increase in LFTs11

Mean liver enzyme levels during NIASPAN 25-week dose-escalation study.



Combination Therapy

Niaspan®

+ Statin(12,13,14, 15)

1. Has been proven safe and effective in

many trials

2. Some early trials with OTC sustained

release Niacin showed some

rhabdomyolysis and mild increase in

LFTs

3. No rhabdomyolysis or increase in LFTshas been shown with Niaspan® in

combination with a Statin



Advicor™- January 2002

Combination Niaspan® + Lovastatin

(Mevacor ®)= Advicor ™

Current Data from an Ongoing open label dose-

escalating study on Advicor ® with 814 dyslipidemic

patients after one year of treatment 14

– HDL by 41%

– LDL by 45%

– TGs by 42%

– Lp(a)

by 18%

No cases of myopathy and <1% with LFTs

9% of patients discontinued due to Flushing



“Large” RCT

Patient population n=1 (My girlfriend)

Treatment=

1. 1st month

Slo-Niacin (OTC extended release)

titrated up to 1 gram over 1 month

2. 2nd month

Niaspan® 500mg-2.5wks,1gram-1.5wks

3. 3 months

Niaspan® 1gram qhs

(Currently on 1gm Niaspan® qhs)



Amazing Results

LDL by 37% (206 -> 130)

HDL by 40% (40->56)

Triglycerides by 45% (150->83)

Li ’ R lt



Liz’s Results

3/09/01 4/23/01 5/24/01 8/23/01Total

Cholesterol

276 228 208 203

LDL 206 154 137 130

HDL 40 36 41 56

Triglycerides 150 187 147 83



CHD Risk

Decreased from:

1.9x (3/9/01)

to

0.6x (8/23/01)

Summary



Summary LDL is not the only Lipoprotein that should be

considered for CHD Risk- HDL, TGs, Lp(a) should be

evaluated and consideration should be given toLDL/HDL sub-class testing with a strong FH of

sudden cardiac death

Niaspan® is close to a “Magic Bullet” by moving ALLLipoproteins in the right direction, especially HDL,

and doing positive things in areas we are not

currently testing like Lp(a) and LDL/HDL subclasses

Advicor™- is being shown to have phenomenal

effects on the Lipid profile and (pending FDA

approval in the second half of 2001) will become a

formidable weapon in the war against CHD

References



References1. Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in

Adults. Summary of the second report of the National Cholesterol Education

Program (NCEP) Expert Panel on Detection, Evaluation, and Treatment of High

Blood Cholesterol in Adults (Adult Treatment Panel || ). JAMA. 1993;269:3015-30232. Phillips NR, waters D, Havel RJ. Plasma lipoproteins and progression of coronary

artery disease evaluated by angiography and clinical events. Circulation

1993;88:2762-2770

3. NIH Consensus Development Panel on Triglyceride, High-Density Lipoprotein, and

Coronary Heart Disease. Triglyceride, high-density lipoprotein and coronary heart

disease. JAMA. 1993;269:505-510.

4. Bostom AG, Cupples LA, Jenner JL, et al. elevated plasma lipoprotein(a) and

coronary heart disease in men aged 55 years and younger: a prospective study.

JAMA. 1996;276:544-548.

5. Lipid research clinics program. The lipid research clinics clinics coronary primary

prevention trial results. 1 Reduction in incidence of coronary heart disease. JAMA

1984;251:351-364

6. Multiple risk factor intervention trial research group: Multiple risk factor intervention

trial: Risk factor changes and mortality results. JAMA 1982;248:1465-1477

7. Gordon T, Castelli WP, Hjortland MC, et.al High density lipoprotein as a protective

protective factor against coronary heart disease: The Framingham Study. Am J MED

1977;62:707-714

References (2)



References (2)8. Rubins HB,Robins SJ, Collins D, Fve CL, Anderson JW, Elam MB, Faas FH,

Linares E, Schaefer EJ, Schectman G, Wilt TJ, Wittes J. Gemfibrozil for thesecondary prevention of coronary heart disease in men with low levels of high-density lipoprotein cholesterol. Veterans Affairs High-Density Lipoprotein

Cholesterol Intervention Trial Study Group. N Engl J Med. 1999 Aug5;341(6):410-416.

9. Morgan JM, Capuzzi DM, Guyton JR, et al. Treatment effect of Niaspan®, acontrolled-release niacin, in patients with hypercholesterolemia: a placebo-controlled trial. J Cardiovasc Pharmacol Therapeut . 1996;1:195-202

10. Knopp RH, Alagona P, Davidson M. at al. Equivalent efficacy of a time-releaseform of niacin (NIASPAN) given Once-a-Night versus plain naicin in the

managment of hyperlipidemia metabolism 1998;47:1097-110411. Goldberg A, Alagona P, Capuzzi DM, et al. Multiple dose efficacy and safety of

an extended-release form of niacin in the management of Hyperlipidemia. AMJ Cardiol 2000;85:1100-1105.

12. Guyton JR, Goldberg AC, Kreisberg RA, et al effectivness of once nightly dosingof extended-release niacin alone and in combination for hypercholesterolemia;

AM J Cardiol 1998;82 737-743.

13. Guyton JR, Capuzzi DM. Treatment of hyperlipidemia with combined niacin-statin regimens. AM J Cardiol 1998;82:824-844.

14. Wolfe ML, Vartanian SF, Ross JL, Bansavich LL, Mohler ER 3rd, Meagher E,Friedrich CA, Rader DJ. Safety and effectiveness of Niaspan when addedsequentially to a statin for treatment of dyslipidemia. Am J Cardiol. 2001 Feb15;87(4):476-9, A7.

15. Kayshyap ML, Evans R, Simmons PD, Kohler RM, McGovern ME. New

combination niacin/statin formulation shows pronounced effects on major lipoproteins and is well-tolerated. J Am Coll Cardiol 2000;35(suppl A):326A.

V I W b i



Very Important Websites

http://www.nhlbi.nih.gov/guidelines/cholesterol/profmats.htm

www.niaspan.com

www.kospharm.com

www.Lipoprofile.com

www.berkelyheartlab.com

www.JasonLogan.com



http://www.niaspan.com/

http://www.kospharm.com/

http://www.lipoprofile.com/

http://www.berkelyheartlab.com/

http://www.jasonlogan.com/

http://www.jasonlogan.com/

http://www.berkelyheartlab.com/

http://www.lipoprofile.com/

http://www.kospharm.com/

http://www.niaspan.com/





Professionals

The Guidelines

Related Tools

ATP III Executive Summary

ATP III Full Report (coming soon)

ATP III At-A-Glance: Quick Desk Reference

ATP III Slide Show

Palm OS Interactive Tool

10-year Risk Calculator (online version)

10-year Risk Calculator (downloadable

version)

NCQA/NHLBI Conference Web site

http://www.nhlbi.nih.gov/guidelines/cholesterol/atp_iii.htm

http://www.nhlbi.nih.gov/guidelines/cholesterol/dskref.htm

http://hin.nhlbi.nih.gov/ncep_slds/menu.htm

http://hin.nhlbi.nih.gov/atpiii/atp3palm.htm

http://hin.nhlbi.nih.gov/atpiii/calculator.asp?usertype=prof

http://hin.nhlbi.nih.gov/atpiii/riskcalc.htm

http://hin.nhlbi.nih.gov/cholesterol/


http://www.nhlbi.nih.gov/guidelines/cholesterol/riskcalc.htm

http://207.238.28.154/NHLBI-RiskAsessment/default.asp?usertype=prof

http://www.nhlbi.nih.gov/guidelines/cholesterol/atp3palm.htm









http://www.nhlbi.nih.gov/guidelines/cholesterol/riskcalc.htm




http://207.238.28.154/NHLBI-RiskAsessment/default.asp?usertype=prof

http://hin.nhlbi.nih.gov/atpiii/atp3palm.htm


http://hin.nhlbi.nih.gov/ncep_slds/menu.htm
















Download our ATP III Cholesterol Management Implementation Tool for Palm OS

The Palm OS program for application of the Third Report of the National Cholesterol Education Program (NCEP)

Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (Adult TreatmentPanel III) is now available.

This interactive guideline tool will assist the clinician in implementing the ATP III Cholesterol Guidelines at the point of

care.

The program also contains usable information from ATP III including:

• ATP III classification of lipid levels.

• ATP III CHD risk assessment.

•Therapeutic Lifestyle Changes (TLC).

•Drug therapy for lipid lowering.•Information on the metabolic syndrome.

•Issues for special populations.

Li b f Ni ®



Liz before Niaspan®

Li f Ni ®



Liz after Niaspan®

Treating Hypercholesterolemia



Treating Hypercholesterolemia

Has Its Benefits!!!

Thanks For Your Attention!



Thanks For Your Attention!

Documents

Niacin Presentation