Managing the Patient with High Triglycerides:

Assessment and Treatment Strategies

February 6, 2014

Ft. Lauderdale, FL

Faculty Harold E. Bays, MD, FTOS, FACE, FNLA

Michael Miller, MD, FACC, FAHA

Session 5: Managing the Patient with High Triglycerides: Assessment and Treatment Strategies Learning Objectives 1. Discuss the role of elevated triglyceride (TG) levels in the assessment and diagnosis of dyslipidemia,

including cardiovascular risk factors 2. Apply best practices in the attainment of TG levels, including the role of fasting and nonfasting states in accurate

evaluation 3. Evaluate the management of hypertriglyceridemia through greater adherence to evidenced based practices and

accepted guidelines 4. Select potential new and emerging therapeutic approaches to manage TG-based dyslipidemia, mixed dyslipidemia,

and associated cardiovascular risk Faculty

Harold E. Bays, MD, FTOS, FACE, FNLA Medical Director and President Louisville Metabolic and Atherosclerosis Research Center Louisville, Kentucky

Dr Harold Bays is medical director and president of Louisville Metabolic and Atherosclerosis Research Center (L-MARC) in Louisville, Kentucky. He earned his medical degree and completed his internship and residency in internal medicine, He then received his fellowship in endocrinology and metabolism at the University of Louisville School of Medicine. Dr Bays has served as an investigator in over 400 Phase I through IV clinical trials for treatments for high cholesterol and other dyslipidemias, obesity, diabetes mellitus, hypertension, osteoporosis, and other metabolic and hormonal disorders. He has written, or served as a contributing author for, over 180 scientific manuscripts and book chapters; and authored over 100 scientific abstracts. His publications have appeared in such peer reviewed journals as the New England Journal of Medicine, Obesity/Obesity Research, Journal of Clinical Endocrinology and Metabolism, and Cell Metabolism.

Michael Miller, MD, FACC, FAHA Professor, Departments of Medicine, Epidemiology & Public Health University of Maryland School of Medicine Director, Center for Preventive Cardiology University of Maryland Medical Center Baltimore, Maryland

Dr Michael Miller is a professor in the departments of medicine, epidemiology & public health at the University of Maryland School of Medicine, Baltimore, Maryland. In addition, he is director of the center for preventive cardiology at the University of Maryland Medical Center. Dr Miller earned his MD from The University of Medicine and Dentistry of New Jersey. Following a medical residency at the University of Cincinnati Hospital, he completed two fellowships at Johns Hopkins, one in lipoprotein metabolism and the second in cardiovascular disease. His major research interests are disorders of lipid and lipoprotein metabolism, molecular studies of HDL cholesterol, triglycerides and the postprandial response to dietary fat, nontraditional coronary risk factors, and clinical trials to reduce atherosclerosis. Dr Miller has authored more than 250 original articles, book chapters and other publications. Original research articles have appeared in BMJ, Circulation, JACC, JAMA, NEJM, PNAS, and Science. He is the coauthor of “The Practice of Coronary Disease Prevention” and the “AMA Guide to Preventing and Treating Heart Disease.”

Faculty Financial Disclosure Statements The presenting faculty reports the following: Dr Bays receives research grants from Alere, Amarin, Amgen, Ardea Inc., Boehringer Ingelheim, California Raisin Board, Catabasis, Eisai, Elcelyx, Eli Lilly, Esperion, Forest, Gilead, Given, GlaxoSmithKline, High Point Pharmaceuticals, LLC, Hoffman LaRoche, Home Access, Isis, Janssen, Merck, Micropharma Limited, Nektar, Novartis, Novo Nordisk, Omthera, Orexigen Therapeutics, Pfizer, Pronovo, Regeneron, Takeda, TIMI, Transtech Pharma, Inc., Trygg Pharmaceuticals, VIVUS, WPU, and Xoma; Consulting Fees from Amarin, Amgen, AstraZeneca, Bristol-Myers Squibb, Catabasis, Daiichi Sankyo, Inc., Eisai, Isis, Merck, Novartis, Pronovo, VIVUS, and WPU; and speaker fees from Amarin, Bristol-Myers Squibb, Daiichi Sankyo, Inc., Eisai, Merck, and VIVUS. Dr Miller receives consulting fees from Amarin. Education Partner Financial Disclosure Statement The content collaborators at Medtelligence, LLC report the following: Ben Caref, PhD, Managing Partner and Chief Medical Officer, develops content and has no financial relationships to disclose. Pamela J. Clark, Director of Editorial Services, provides editorial assistance and has no financial relationship to disclose. Suggested Reading List American Diabetes Association. Standards of medical care in diabetes–2012. Diabetes Care. 2012;35(Suppl 1):S11-S63. Ballantyne CM, Bays HE, Kastelein JJ, et al. Efficacy and safety of eicosapentaenoic acid ethyl ester (AMR101) therapy in statin-treated patients with persistent high triglycerides (from the ANCHOR study). Am J Cardiol. 2012;110(7): 984-992. Bays HE, Ballantyne CM, Kastelein JJ, et al. Eicosapentaenoic acid ethyl ester (AMR101) therapy in patients with very high triglyceride levels (from the Multi-center, plAcebo-controlled, Randomized, double-blINd, 12-week study with an open-label Extension [MARINE] trial). Am J Cardiol. 2011;108(5):682-690. Brinton EA, Ballantyne CM, Bays HE, et al. Effects of icosapent ethyl on lipid and inflammatory parameters in patients with diabetes mellitus-2, residual elevated triglycerides (200–500 mg/dL), and on statin therapy at LDL-C goal: the ANCHOR study. Cardiovasc Diabetol. 2013;12(1):100. Brunzell JD, Davidson M, Furberg CD, et al. Lipoprotein management in patients with cardiometabolic risk: consensus conference report from the American Diabetes Association and the American College of Cardiology Foundation. J Am Coll Cardiol. 2008;51(15):1512-1524. James PA, Oparil S, Carter BL, et al. 2014 Evidence-Based Guideline for the Management of High Blood Pressure in Adults: Report From the Panel Members Appointed to the Eighth Joint National Committee (JNC 8). JAMA. 2013;Dec 18 [Epub ahead of print]. Jellinger PS, Smith DA, Mehta AE, et al; for the AACE Task Force. American Association of Clinical Endocrinologists' Guidelines for Management of Dyslipidemia and Prevention of Atherosclerosis. Endocr Pract. 2012;18(Suppl 1):1-78. Miller M, Stone NJ, Ballantyne C, et al. Triglycerides and cardiovascular disease: a scientific statement from the American Heart Association. Circulation. 2011;123(20):2292-2333. Sniderman AD, Williams K, Contois JH, et al. A meta-analysis of low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, and apolipoprotein B as markers of cardiovascular risk. Circ Cardiovasc Qual Outcomes. 2011;4(3):337-345.

Stone NJ, Robinson J, Lichtenstein AH, et al. 2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. Circulation. 2013; Nov 12. [Epub ahead of print] Sarwar N, Sandhu MS, Recketts SL, et al: for the Triglyceride Coronary Disease Genetics Consortium and Emerging Risk Factors Collaboration. Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies. Lancet. 2010;375(9726):1634-1639.

1

Managing the Patient with High Triglycerides: Assessment and Treatment Strategies

SPEAKERSHarold E. Bays, MD, FTOS, FACE, FNLA

Michael Miller, MD, FACC, FAHA

SESSION 52:30–3:45pm

Presenter Disclosure Information

►Dr Bays receives research grants from Alere, Amarin, Amgen, ArdeaInc., Boehringer Ingelheim, California Raisin Board, Catabasis, Eisai, Elcelyx, Eli Lilly, Esperion, Forest, Gilead, Given, GlaxoSmithKline, High Point Pharmaceuticals, LLC, Hoffman LaRoche, Home Access, Isis, Janssen, Merck, Micropharma Limited, Nektar, Novartis, Novo Nordisk, Omthera, Orexigen Therapeutics, Pfizer, Pronovo, Regeneron, Takeda, TIMI, Transtech Pharma, Inc., TryggPharmaceuticals, VIVUS, WPU, and Xoma; Consulting Fees from Amarin, Amgen, AstraZeneca, Bristol-Myers Squibb, Catabasis, Daiichi Sankyo, Inc., Eisai, Isis, Merck, Novartis, Pronovo, VIVUS, and WPU; and speaker fees from Amarin, Bristol-Myers Squibb, Daiichi Sankyo, Inc., Eisai, Merck, and VIVUS.

►Dr Miller receives consulting fees from Amarin.

The following relationships exist related to this presentation:

Presenter Disclosure Information

Off-Label/Investigational Discussion

► In accordance with pmiCME policy, faculty have been asked to disclose discussion of unlabeled or unapproved use(s) of drugs or devices during the course of their presentations.

Managing the Patient with High Triglycerides: Assessment and Treatment Strategies

February 6, 2014

Drug Names

Generic name Brand name(s)

Atorvastatin Atorvastatin Calcium, Caduet, Lipitor

Bezafibrate none

Estrogen various

Ezetimibe various

Fenofibrate Antara, Fenoglide, Lipofen, Tricor, Triglide, Trilipix

Fluvastatin Fluvastatin Sodium, Lescol, Lescol XL

Gemfibrozil Gemfibrozil, Lopid

Icosapent Ethyl Vascepa

Isotretinoin various

Lovastatin Advicor, Altoprev, Lovastatin, Mevacor

Generic name Brand name(s)

Metformin various

NiacinNiacin/laropiprant

various

Omega-3-acidethyl esters

Lovaza, Omacor, Vascepa

Pravastatin Pravachol, PravastatinSodium, Pravigard PAC

Rosuvastatin Crestor, Rosuvastatin Calcium, Rosuvastatin Zinc

Simvastatin Zocor, simvastatin

Tamoxifen Nolvadex, Soltamox,Tamoxifen Citrate

Thiazide diuretic various

Learning Objectives

• Discuss the role of elevated triglyceride (TG) levels in the assessment and diagnosis of dyslipidemia, including cardiovascular risk factors

• Apply best practices in the attainment of TG levels, including the role of fasting and non-fasting states in accurate evaluation

• Evaluate the management of hypertriglyceridemia (HTG) through greater adherence to evidence based practices and accepted guidelines

• Select potential new and emerging therapeutic approaches to manage TG-based dyslipidemia, mixed dyslipidemia, and associated cardiovascular risk

2

What Is the Relationship of Hypertriglyceridemia to Increased CVD Risk?

Michael Miller, MD, FACC, FAHAProfessor, Departments of Medicine, Epidemiology, & Public HealthUniversity of Maryland School of MedicineDirector, Center for Preventive CardiologyUniversity of Maryland Medical CenterBaltimore, MD

Prevalence (%) of HTG by Age, Sex, and Ethnicity in NHANES 1999–2008

TG Cut Points, mg/dLa

Demographic ≥150 ≥200 ≥500

Overall (age ≥20 yrs) 31 16 1.1

Men 35 20 1.8

Womenb 27 13 0.5

Mexican American 35 20 1.4

Non-Hispanic, black 16 8 0.4

Non-Hispanic, white 33 18 1.1

Use of TG-lowering medicationsc 18

a Percentage of participants. bExcludes pregnant women. Miller M et al. Circulation. 2011;123:2292-333.c Includes fenofibrate, gemfibrozil, niacin, or statin. Ford ES et al. Arch Intern Med. 2009;169:572-8.dUS Census Age 20 and above, July 1, 2010, was 226,113,653. HTG=hypertriglyceridemia; NHANES=National Health and Nutrition Examination Survey; TG=triglyceride(s); yrs=years.

70 million persons, or ~1/3 of US adults, have elevated TG (≥150 md/dL)d

Fattyliver

Three Atherogenic Consequences of HTG

TG

CE

CETP HDL

Hepatic Lipase

Kidney

Rapid Lossof Apo A-I

HDL-C, HDL-P, & Apo A-I

SDHDL

3

TG

VLDL-C1

CE

TG

CETP

SDLDL

LDL size

Apo B & LDL-PHepatic Lipase

LDL

2

VLDL

FFA/TGand

Fructose(glucose)

CentralAdiposity

FFA /TG

↑VLDL Synthesis

Apo=apolipoprotein; CE=cholesterol ester; CETP=CE transfer protein; FFA=free fatty acid; HDL=high-density lipoprotein; HDL-C=HDL cholesterol; HDL-P=HDL particle; LDL=low-density lipoprotein; LDL-P=LDL particle; SD=small dense; VLDL=very-low-density lipoprotein; VLDL-C=VLDL cholesterol.

Fatty liver & ↑VLDL synthesis are key to ↑TG and consequences

“Atherogenic Dyslipidemia”

1. ↑TG / VLDL-C2. SD LDL / ↑LDL-P3. ↓HDL-C & Apo A-I

112233

Fattyliver

Postprandial TG (Remnants) Increased in CAD Patients

CAD=coronary artery disease. Patsch JR et al. Arterioscler Thromb. 1992;12:1336-45.

Pla

sma

TG

(m

g/d

L)

Hours after meal

*P=0.025; †P0.001.

*

†

†

CAD (n=61)

0

100

200

300

400

0 2 4 6 8

No CAD (n=40)

Elevated TG Associated with ↑SD LDL-P, ↓HDL-C, and ↑Non-HDL-C

Apo B

LDL=130 mg/dL

Fewer Particles More Particles

CE

More Apo B

TC=total cholesterol. Otvos JD et al. Am J Cardiol. 2002;90:22i-29i.

Fasting Lipid Panel:TC 198 mg/dLLDL-C 130 mg/dLTG 90 mg/dLHDL-C 50 mg/dLNon-HDL-C 148 mg/dL

Fasting Lipid Panel:TC 210 mg/dLLDL-C 130 mg/dLTG 250 mg/dLHDL-C 30 mg/dLNon-HDL-C 180 mg/dL

Association Between BMI and HTGNHANES 1999–2004

TG Concentration (mg/dL)

BMI (kg/m2)

<150(n=3250)

<200(n=4057)

≥150(n=1744)

≥200(n=937)

<25 42.7 39.0 20.1 17.5

25 to <30 31.6 33.3 39.9 39.6

≥30 25.6 27.7 39.9 42.9

BMI=body mass index.Miller M et al. Circulation. 2011;123:2292-333.

Percent of participants within a TG category as a function of BMI status

~2.5 greater prevalence

3

CVD=CV disease; EWET=enlarged waist with elevated TG; MetS=metabolic syndrome; NCEP=National Cholesterol Education Program. Tankó LB et al. Circulation. 2005;111:1883-90.

MetS-NCEP +

EWET –

CV P<0.001

-2 0 2 4 6 8 10

0.7

0.8

0.9

1.0

1.1

Follow-up Time (yrs)

Cu

mu

lati

ve S

urv

ival

Cu

mu

lati

ve S

urv

ival

0.7

0.8

0.9

1.0

1.1

-2 0 2 4 6 8 10

P<0.001

MetS-NCEP –

EWET +

CV

Kaplan-Meier curves indicating cardiovascular (CV) event rates in women with (n=88) or without (n=469) EWET or with (n=100) or without (n=433) MetS as per 2001 NCEP. EWET=Waist ≥88 cm and TG ≥128 mg/dL.

Follow-up Time (yrs)

Enlarged Waist Combined with Elevated TG May Predict CVD as Well as MetS in Menopausal Women

PROVE IT-TIMI 22 Trialb

TG <150 mg/dL Associated with Lower Risk of CHD Eventsa Independent of LDL-C Level

Achieving both low LDL-C and low TG (<150 mg/dL) may be important therapeutic strategies in patients after acute coronary syndrome (ACS)

CH

D E

ven

taR

ate

a

fte

r 3

0 D

ays

c(%

)

aDeath, myocardial infarction (MI), and recurrent ACS. bACS patients on atorvastatin 80 mg or pravastatin 40 mg. cAdjusted for age, gender, low HDL-C, smoking, hypertension (HTN), obesity, diabetes, prior statin therapy, prior ACS, peripheral vascular disease, and treatment. CHD=coronary heart disease; HR=hazard ratio; LDL-C=LDL cholesterol; PROVE IT-TIMI=Pravastatin or Atorvastatin Evaluation and Infection Therapy Thrombolysis In Myocardial Infarction. Miller M et al. J Am Coll Cardiol. 2008;51:724-30.

N=4162

TG <150 TG ≥150

LDL-C ≥70

LDL-C <70

HR: 0.72P=0.017

HR: 0.85P=0.180

HR: 0.84P=0.192

Referent

Lipid values in mg/dL

Low HDL-C and High TGs Increase CVD Risk Even when LDL-C Levels Are Well-Controlled

HDL-C Quintilesa

(mg/dL)

5-yr

Ris

k of

Maj

or

CV

D E

vent

s (%

)

Patients with LDL-C ≤70 mg/dL on statina,b

aOn-treatment level (3 months statin therapy), n=2661.bMean LDL-C 58 mg/dL, mean TG 126 mg/dL.*P=0.03 for differences among quintiles of HDL-C.

Q237 to <42

Q342 to <47

Q5≥55

Q447 to <55

HR vs Q1* 0.85 0.57 0.55 0.61

39% Lower Risk

TG=186 TG=168 TG=150 TG=142 TG=124

TNT=Treating to New Targets.Barter P et al. N Engl J Med. 2007;357:1301-10.

Q1<37

TG values in mg/dL

TNT Study

TG Levels and CHD Risk:Meta-analysis of 29 Studies

*Individuals in top vs bottom third of usual log-TG values, adjusted for at least age, sex, smoking status, lipid concentrations, and (in most studies) blood pressure (BP).

CI=confidence interval. Sarwar N et al. Circulation. 2007;115:450-8.

CHD CasesDuration of Follow-up≥10 yrs 5902<10 yrs 4256

SexMale 7728Female 1994

Fasting StatusFasting 7484Non-fasting 2674

Adjusted for HDL-CYes 4469No 5689

Overall CHD Risk Ratio*Decreased

Risk

CHD Risk Ratio* (95% CI)

1.72 (95% CI 1.56–1.90)

21Increased

Risk

N=262,525

*All measurements in mg/dL. AHA=American Heart Association; ATP=Adult Treatment Panel; NCEP=National Cholesterol Education Program; NIH=National Institutes of Health. Miller M et al. Circulation. 2011;123:2292-33.

TG Revisions between 1984 and 2001

AHA Scientific Statement on TG Classification

TG Designation 1984 NIH Consensus Panel

1993 NCEPATP II

2001 NCEPATP III

Desirable* <250 <200 <150

Borderline High* 250–499 200–399 150–199

High* 500–999 400–999 200–499

Very High* >1000 >1000 >500

AHA Statement in 2011 classified TG <100 mg/dL as “optimal”(SD LDL becomes much more prevalent with TG >100 mg/dL)

Can HTG Cause Atherosclerosis?

Con

• HTG → CVD weaker than LDL-C, partly HDL-C dependent

• Severe HTG from ↑chylomicrons not related to ↑CVD

• TG accumulation not seen in atherosclerotic plaque

• TG-lowering drugs not completely proven to ↓CVD

Pro

• TG-rich lipoproteins are atherogenic (esp. cholesterol-rich remnants)

• TG lipolysis by lipoprotein lipase (LPL) → pro-inflammatory FFA (uptake by CD36 & FA binding proteins to nucleus)

• HTG causes atherogenic changes in LDL and HDL

• TG-lowering drugs ↓CVD in HTG / low HDL-C patients

• TG ~100–800 mg/dL is OFTEN associated with hyper-Apo B (ie, pro-atherogenic state)

FA=fatty acid. Miller M et al. Circulation. 2011;123:2292-333.

4

How Should We Use Lipid Measures to Assess CV Risk in Patients with Dyslipidemia?

Predicting a First Atherosclerotic CV Event

ACC/AHA 2013 Prevention Guidelines CV Risk Calculator. http://clincalc.com/Cardiology/ASCVD/PooledCohort.aspx. Goff DC Jr et al. Circulation. 2013; Nov 12. [Epub ahead of print].

•Calculator uses the Pooled Cohort Equations to estimate the 10-year primary risk of ASCVD among patients without pre-existing cardiovascular disease who are between 40 and 79 years of age

•Patients are considered to be at "elevated" risk if the Pooled Cohort Equations predicted risk is ≥7.5%

•The Pooled Cohort Equations have been proposed to replace the Framingham Risk 10-year CVD calculation

2013 ACC/AHA Guideline: Hypertriglyceridemia

• “Although elevations in LDL-C often occur simultaneously with elevated triglyceride levels, the Panel did not conduct a systematic review on lifestyle and drug therapies for the treatment of elevated triglyceride levels.”

• “Marked exacerbations of triglycerides >1,000 mg/dL may indicate those who may develop very marked triglyceride elevations that could trigger hyperlipidemic pancreatitis. Because of the increased risk for pancreatitis at these triglyceride levels, drug therapy specifically to lower triglycerides is advised. The fibrates—fenofibrate and gemfibrozil—are considered first-line agents for triglyceride lowering (see Safety). Marine omega-3 fatty acids (docosahexaenoic acid [DHA] and EPA) in doses of 3 to 4 g and niacin 2 g also have been shown to reduce triglycerides in individuals with severe hypertriglyceridemia.”

EPA=eicosapentaenoic acid. Stone NJ et al. Circulation. 2013; Nov 12. [Epub ahead of print].

Targets for Therapy after LDL-C Goal in Patients with TG 200 mg/dL

RF=risk factor.Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults. JAMA. 2001;285:2486-97.

Patient CategoryLDL-C target

(mg/dL)Non-HDL-C target

(mg/dL)

No CHD, <2 RFs <160 <190

No CHD, ≥2 RFs <130 <160

CHD or CHD risk equivalent

<100 <130

Summary and Conclusions

HTG (and low HDL-C)

• HTG and low HDL-C (with high Apo B, LDL-P, and SD LDL) is the “atherogenic dyslipidemia” common in insulin resistance/MetS and T2DM

• Both HTG and low HDL-C strongly predict CVD risk, even with excellent LDL-C control on a statin

T2DM=type 2 diabetes mellitus.

Summary and Conclusions

After assessing for ASCVD with risk calculator, guideline recommendations for statin Rx include

1. Individuals with clinical ASCVD

2. Individuals with primary elevations of LDL ≥190 mg/dL

3. Individuals 40 to 75 years of age with diabetes and an LDL 70 to 189 mg/dL without clinical ASCVD

4. Individuals without clinical ASCVD or diabetes who are 40 to 75 years of age with LDL 70 to 189 mg/dL and a 10-year ASCVD risk of 7.5% or higher

ACC/AHA 2013 Prevention Guidelines CV Risk Calculator. http://clincalc.com/Cardiology/ASCVD/PooledCohort.aspx. Goff DC Jr et al. Circulation. 2013; Nov 12. [Epub ahead of print]. Stone NJ et al. Circulation. 2013; Nov 12. [Epub ahead of print].

5

How Should HTG be Managed?

Harold E. Bays, MD, FTOS, FACE, FNLA Medical Director and President Louisville Metabolic and Atherosclerosis Research Center Louisville, KY

ATP III Treatment Recommendations for Elevated TG

TG (mg/dL)

ATP III Classification

Primary Target of Therapy

Treatment Recommendations

150–199 Borderline high LDL-C goal Weight and Physical activity

200–499 High LDL-C goal

Weight and Physical activity

Consider non-HDL-C goal:LDL-C with statin or VLDL-C with

niacin or fibrateSugar and carbs*

≥500 Very high

TGto prevent

acute pancreatitis

Very low fat diet (fat ≤15% total calories)Weight and Physical activityAdd niacin or fibrates(+OM-3 as per FDA indication*)

*Not in ATP III statement. carbs=carbohydrates; FDA=US Food and Drug Administration; OM=omega. NCEP ATP III. Circulation 2002;106:3143-421.

Primary Causes of HTG

Relatively common• Familial combined hyperlipidemia (FCHL)

– Variable phenotype (↑TG alone, or ↑TC alone, or both increased)– Associated with ↑↑CVD and ↑central obesity– Multiple genetic associations of unclear causal significance– “Hyper-Apo B”

• Familial HTG (FHTG)– ↑TG alone (not TC)– Associated with ↑CVD if ↑central obesity / MetS– Largely due to ↑hepatic VLDL production– Apo B is usually normal

Rare• LPL deficiency

• Apo C-II deficiency

• Familial dysbetalipoproteinemia (Type III)

• GPIHBP1 deficiency

GPIHBP=glycophosphatidylinositol-anchored HDL-binding protein. Bays HE. In: Kwiterovich PO Jr, ed. The Johns Hopkins Textbook of Dyslipidemia. 1st ed. Lippincott Williams & Wilkins;2010:245-57.

Note: FCHL and FHTG may NOT be distinct entities

Secondary Causes of HTG

HIV=human immunodeficiency virus. Bays HE. In: Kwiterovich PO Jr, ed. The Johns Hopkins Textbook of Dyslipidemia. 1st ed. Lippincott Williams & Wilkins;2010:245-57.

Cause Clinically useful details

Positive energy balance Saturated fat or Glycemic index content

Carbohydrate intake Simple sugars (fructose, sucrose, etc.) & dietary fiber

Adiposopathy (especially visceral adiposity)

Impaired adipogenesis, adipocyte hypertrophy, & adipose tissue dysfunction

Diabetes mellitus Especially if poorly controlled

HypothyroidismOnly if not adequately controlled with thyroid replacement therapy

Nephrotic syndrome

Medications

Antiretroviral regimens (for HIV) Some phenothiazines and 2nd-generation antipsychoticsNonselective beta-blockers Thiazide diureticsOral estrogen, tamoxifenGlucocorticoids and Isotretinoin

Recreational drugs Alcohol (esp. with fatty liver) and marijuana (Apo C-III)

Pharmacologic Therapy for Very High TG Levels

Drug Class

High TG Indications*

Select Adverse Effects (AEs)TG

>500 mg/dL

Type IV Hyper-

lipidemia

Fenofibratea Dyspepsia, various upper gastrointestinal complaints, cholesterol, gallstones, myopathy

Extended-release Niacin (ERN)b

Flushing, pruritus, diarrhea, vomiting,

hyperglycemia, hyperuricemia or gout, dyspepsia and exacerbation of peptic ulcer, hepatotoxicity

*Data from individual product labeling for each drug in patients with very TG. a145 mg per day. b2 grams per day. Fredrickson DS et al. Ann Intern Med. 1975;82:150-7. Miller M et al. Circulation. 2011;123:2292-333.

Pharmacologic Therapy for Very High TG Levels

Drug Class

High TG Indications*

Select Adverse EffectsTG >500

mg/dL

Type III Hyper-

lipidemia

Type IVHyper-

lipidemia

OM-3 FA (EPA / DHA)a Eructation, dyspepsia, taste

perversion

OM-3 FA (EPA only)a Arthralgia

Statins b cMyalgia, myopathy (rare),

rhabdomyolysis (very rare), A1c, cognitive impairment

*Data from individual product labeling for each drug in patients with very TG. a4 grams per day. bAtorvastatin, rosuvastatin, and simvastatin. cAtorvastatin and simvastatin. A1c=glycosylated hemoglobin.Fredrickson DS et al. Ann Intern Med. 1975;82:150-7. Miller M et al. Circulation. 2011;123:2292-333.

6

Lipid Effects of Drug Classes in Subjects with Primary Hyperlipidemia / Mixed Dyslipidemia and Isolated HTG

*Range, %.NR=not reported.Maki KC, Bays HE, Dicklin MR. J Clin Lipidol. 2012;6:413-26.

Type of dyslipidemia/ medication TG* LDL-C* HDL-C*

Non-HDL-C*

Mixed dyslipidemia• Statins• Omega-3 fatty acids• Fenofibrate, fenofibric acid and gemfibrozil

• Niacin

–10 to –37–19 to –44–24 to –36

–5 to –38

–26 to –63–6 to +25–5 to –31

–3 to –17

+5 to +16–5 to +7

+10 to +16

+10 to +26

–44 to –60–1 to –7

–17

NR

Isolated hypertriglyceridemia• Statins• Omega-3 fatty acids• Fenofibrate, fenofibric acid and gemfibrozil

–21 to –52–26 to –52–46 to –62

–27 to –45+17 to +49

+3 to +47

+3 to +22+9 to +14

+18 to +23

–29 to –52–10 to –14NR

Risk Difference vs Placebo of Hypertriglyceridemic Subgroups from Large-scale, Primary and Secondary CVD Prevention Trials that Used Statins

*Actual P-value was not reported; CARE=Cholesterol and Recurrent Events Trial; CTT=Cholesterol Treatment Trialists; JUPITER=Justification for the Use of Statins in Primary Prevention: An Intervention Trial Evaluating Rosuvastatin; NS=not significant; PPP=Prospective Pravastatin Pooling; 4S=Scandinavian Simvastatin Survival Study; WOSCOPS=West of Scotland Coronary Prevention Study. Maki KC, Bays HE, Dicklin MR. J Clin Lipidol. 2012;6:413-26.

Statin Trials DrugMedian

follow-upRisk difference

vs placebo95% CI

(P-value)

WOSCOPSHigh TG subgroup

Pravastatin 5 yrs–31%

–32%

–17, –43 (<0.001)

–12, –47 (0.003)

CAREHigh TG subgroup

Pravastatin 5 yrs–24%

–15%

–9, –36 (0.003)

1, –29 (0.07)

PPP ProjectHighest TG tertile subgroup

Pravastatin 5–6 yrs–23%

–15%

–18, –28 (<0.001)

–2, –26 (0.029)

4SDyslipidemic subgroup

Simvastatin 5 yrs–34%

–52%

–25, –41 (<0.001)

–31, –67 (<0.001)

JUPITEROlder subjects with TG subgroup

Rosuvastatin 5 yrs–44%

–21%

–31, –54 (<0.001)

NR (NS)*

CTT CollaboratorsHighest TG tertile subgroup

Simvastatin/ pravastatin/ lovastatin/ atorvastatin/ fluvastatin

5 yrs–21%

–24%

–19, –23 (<0.001)

–17, –23 (<0.001)

Trial DrugMedian

follow-upRisk difference

vs placebo 95% CI (P-value)

Fibrate trials:HHS

High TG, high LDL-C/HDL-C subgroupHigh TG, high BMI subgroup

BIPHigh TG subgroup

VA-HITHigh TG subgroup

FIELDHigh TG subgroupHigh TG, low HDL-C subgroup

ACCORDHigh TG, low HDL-C subgroup

Gemfibrozil

Bezafibrate

Gemfibrozil

Fenofibrate

Fenofibrate

5 yrs

6 yrs

5 yrs

5 yrs

5 yrs

–34%–72%–71%

–9%–40%

–22%–27%

–11%–23%–27%

–8%–31%

–8.2, –52.6 (<0.02)NR (<0.05)*–43, –85 (<0.001)

NR (NS)NR (0.02)

–7, –35 (0.006)–7, –42 (0.01)

–25, 5 (NS)–6, –37 (<0.01)–9, –42 (0.005)

–21, 8 (NS)NR (<0.05)*

Fish oil trial: JELISHigh TG, low HDL-C subgroup

EPA 5 yrs–19%

–53%

–5, –31 (0.011)

–2, –77 (0.043)

Niacin trial: AIM-HIGH Niacin 3 yrs +2% –31, 21 (NS)

*Actual P-value was not reported. ACCORD=Action to Control Cardiovascular Risk in Diabetes; AIM-HIGH=Atherothrombosis Intervention in MetS with Low HDL/High TGs: Impact on Global Health Outcomes; BIP=Bezafibrate Infarction Prevention; FIELD=Fenofibrate Intervention and Event Lowering in Diabetes; HHS=Helsinki Heart Study; JELIS=Japan EPA Lipid Intervention Study; VA-HIT=Veterans Affairs HDL Intervention Trial. Maki KC, Bays HE, Dicklin MR. J Clin Lipidol. 2012;6:413-26.

Risk Difference of Hypertriglyceridemic Subgroups vs Placebo from Large-scale, Primary and Secondary CVD Prevention Trials that Used Fibrates, Fish Oil, and Niacin

MI=myocardial infarction. Boden WE et al. N Engl J Med. 2011;365:2255-67.

Time (years)

Cu

mu

lati

ve %

wit

h P

rim

ary

Ou

tco

me

0

10

20

30

40

50

0 1 2 3 4

Monotherapy

Combination Therapy

HR 1.02, 95% CI 0.87–1.21Log-rank P value=0.79

N at risk

Monotherapy

Combination Therapy

1696

1718

1581

1606

1381

1366

910

903

436

428

16.2%

16.4%

AIM-HIGH Primary Endpoint: CHD Death, Non-fatal MI, Ischemic Stroke, High-risk ACS, Hospitalization for Coronary or Cerebrovascular Revascularization

*Non-fatal MI or coronary death, any non-fatal or fatal stroke, coronary or non-coronary artery surgery or angioplasty. HPS2-THRIVE=Heart Protection Study 2 Treatment of HDL to Reduce the Incidence of Vascular Events; LRPT=laropiprant; SDM=standard deviation of the mean. Armitage J. Paper presented at ACC.13: American College of Cardiology 62nd Annual Scientific Session. March 9, 2013.

LipidMean (SDM) at

baseline, mg/dL

TC 128 (22)

Direct LDL 63 (17)

HDL-C 44 (11)

TG 125 (74)

Baseline Lipids on Statin-based Rx

HPS2-THRIVE: Randomized Placebo-controlled Trial of ERN and LRPT

“Significant excesses of serious AEs due to known and unrecognised side-effects of niacin. Over 4 years, ER niacin / laropiprant caused serious AEs in ~30 patients per 1000.”

Years of Follow-up

Pa

tien

ts S

uff

erin

g E

ven

ts (

%)

15.0%

0 1 2 3 4 0

5

10

15

20

14.5%

Placebo ERN / LRPT

Log-rank P=0.29Risk ratio 0.96 (95% CI 0.90–1.03)

Effect of ERN / LRPT on Major Vascular Events (MVEs)*

N=25,673 with Pre-existing CVD

The average patient had NONE of the usual lipid indications for niacin

OM-3 Ethyl Esters and Lipid Levels in Patients with TG >500 mg/dL

Pooled analysis (N=82).Harris WS et al. J Cardiovasc Risk 1997;4:385-91 and Pownall HJ et al. Atherosclerosis 1999;143:285-97.

Placebo OM-3 Acid Ethyl Esters (4 g/day)

Baseline(mg/dL)

TG816

HDL-C22

Non-HDL-C27

TC296

VLDL-C175

LDL-C89

P<0.0001 P=0.0002

P=0.0015 P=0.0059 P<0.0001

P<0.0001

–45.0

6.70.0

9.1

–3.6

–13.8– 9.7

– 1.7 – 0.9

– 42.0

– 4.8

45.0

Ch

ang

e in

Med

ian

Lev

els

7

Statin + EPA+DHA: COMBOS Primary and Secondary Efficacy Results

Me

dia

n C

han

ge

fro

m B

asel

ine

(%)

TG LDL-C HDL-CVLDL-C

Additions to baseline simvastatin therapy:

5

–5

–10

–15

–20

–25

–30

3.4*

–6.3–7.2

–1.2–2.8

–29.5*

0.7‡

0

–27.5*

–4.2†–1.9

Apo BNon-HDL-C

–9.0*

–2.2

*P<0.0001 between groups. †P=0.0232 between groups. ‡P=0.0522 between groups.AEEs=acid ethyl esters; COMBOS=Combination of Prescription Omega-3 with Simvastatin.Davidson MH et al. Clin Ther. 2007;29:1354-67.

OM-3 (Rx) 4 g/d + simvastatin 40 mg/d (n=123)

Placebo + simvastatin 40 mg/d (n=133)

Note: OM-3 AEEs are not FDA approved for TG 200–500 mg/dL

JELIS: Effect of EPA-only on Major Coronary Events in Hypercholesterolemic Patients

Yokoyama M et al. Lancet. 2007;369:1090-8.

No. at Risk

Control

EPA

0 1 4 5 Years

9319 8931 8671 8433 8192 7958

9326 8929 8658 8389 8153 7924

Cu

mu

lati

ve

In

cid

en

ce

of

Ma

jor

Co

ron

ary

Ev

en

ts (

%)

4

P=0.011

Statin + EPA

Statin only3

2

1

0

HR (95% CI): 0.81 (0.69–0.95)

↓

2 3

–19%

18,645 patients with TC ≥251 mg/dL recruited in Japan between 1996 and 1999 received 1800 mg of EPA daily with statin or statin only. Statin dose was up to 20 mg pravastatin or 10 mg simvastatin.

CABG=coronary artery bypass graft; HTN=hypertension.Saito Y et al. Atherosclerosis. 2008;200:135-40.

JELIS Patient Subgroup: TG >150 mg/dL and HDL-C <40 mg/dL

Primary endpoint: sudden cardiac death, fatal and non-fatal MI, unstable angina pectoris, angioplasty, stenting, or CABG

HR and P-value adjusted for age, gender, smoking, diabetes, and HTN

MARINE: Icosapent Ethyl (Pure EPA): Median Placebo-adjusted Change from Baseline for Efficacy Endpoints

The MARINE Study: TG >500 mg/dL

TG Non-HDL-C VLDL-C Lp-PLA2 Apo B TC

Me

dia

n P

lace

bo

-ad

just

ed C

han

ge

(%)

LDL-CHDL-C

VLDL-TG

-33.1ǁ

-19.7 †

-17.7ǁ

-8.1*

-28.6‡

-15.3*

-13.6‡

-5.1NS -8.5

†

-2.6NS

-16.3ǁ

-6.8*

-2.3NS

NS5.2

-3.6NS

NS1.5

-25.8†

-17.3NS

4 g/day (n=76)–FDA approved dose

2 g/day (n=73)-36.0

†

-10.1NS

hsCRP

hsCRP=high-sensitivity C-reactive protein; ITT=intention to treat; Lp-PLA=lipoprotein-associated phospholipase A; MARINE= Multi-center, Placebo-controlled, Randomized, Double-blind, 12-week Study with an Open-label Extension. Bays HE et al. Am J Cardiol. 2011;108:682-90. Bays HE et al. Paper presented at: European Society of Cardiology (ESC) Congress 2011; August 29, 2011; Paris, France.

ITT Population

*P<0.05. †P<0.01. ‡P<0.001. ǁP<0.0001. NS = P≥0.05.P-values reflect differences between icosapent ethyl vs placebo.

Icosapent Ethyl

ANCHOR: Icosapent Ethyl (Pure EPA): Median Placebo-adjusted Change from Baseline for Efficacy Endpoints

TGNon-

HDL-C Apo B

Me

dia

n P

lac

eb

o-a

dju

ste

d C

ha

ng

e (

%)

LDL-C HDL-C

–21.5ǁ

– 10.1‡

– 13.6ǁ

– 5.5†

– 9.3ǁ

– 3.8*

– 6.2†

– 3.6NS

– 4.5†

– 2.2NS

254265 8282128128 9193 3837 Baseline values

(mg/dL)

12-week trial in high-risk statin-treated patients (N=702) with residually TG levels (≥200 and <500 mg/dL) despite LDL-C control (≥40 and <100 mg/dL). ANCHOR=Effect of AMR101 (Ethyl Icosapentate) on Triglyceride (Tg) Levels in Patients on Statins With High Tg Levels (≥200 and <500 mg/dL). Ballantyne CM et al. Am J Cardiol. 2012;110:984-92.

*P<0.05. †P<0.01. ‡P<0.001. ǁP<0.0001. NS = P≥0.05.P-values reflect differences between icosapent ethyl vs placebo.

4 g/day (n=233)

2 g/day (n=236)

The ANCHOR Study: TG ≥200 and <500 mg/dL

Note: EPA is notFDA approved for TG 200–500 mg/dL

Icosapent Ethyl

GISSI-P1-2 ORIGIN3 JELIS4REDUCE-IT5

(Ongoing)

OM-3 Type/dose

EPA/DHA1 g/day2

EPA/DHA1 g/day

EPA1.8 g/day

EPA 4 g/day

Population Italian International Japanese International

N 11,324 12,536 18,645 ~8000

Gender 85% male 65% male 31% male Accrual ongoing

Risk Profile Recent MI (≤3 mos; median 16 days)

High CV risk, and IFG, IGT, or T2DM

80% 1o prev; TC ≥6.5 mM; excl. MI ≤6 mos prior

TG >150 mg/dL+CHD or ↑CHD risk

Follow-up 3.5 years 6.2 years (median) 4.6 years (mean) 4–6 years (planned)

Statin Use Minimal 53% in n-3 FA arm, 55% in pbo arm

All on statins(simvastatin or pravastatin)

All on background statins

(LDL-C goal)

Primary End Point

All-cause death, NF MI, NF stroke

Death from CV causes

Major adverse cardiac event

Major adverse cardiac event

ResultRRR 10% (P=0.048)/

15% (P=0.023)

HR=0.98P=0.72

RRR 19% (no minimum TG level) P=0.011

Powered for 15% RRR

LDL-C 2%–3% >control groups 12% both arms 25% in both groups –

Select OM-3 CVD Outcome Studies

1. GISSI-Prevenzione Investigators. Lancet. 1999;354:447-55. 2. www.trialresultscenter.org/study4440-GISSI-P.htm. 3. ORIGIN Investigators. N Engl J Med. 2012;367:309-18. 4. Yokoyama M et al. Lancet. 2007;369:1090-8. 5. http://www.clinicaltrials.gov. excl.=excluded; GISSI=Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico; IFG=impaired fasting glucose; IGT=impaired glucose tolerance; mos=months; NF=non-fatal; ORIGIN=Outcome Reduction with an Initial Glargine Intervention; pbo=placebo; prev=prevention; REDUCE-IT=Reduction of Cardiovascular Events with EPA-Intervention Trial; RR=relative risk; RRR=relative risk reduction.

Note: Trial designs differ so results can not be directly compared.

8

AMR101 4 g/day

Placebo

Study duration ~4–6 yrs

Primary endpoint:

Prevention of 1st major CV

event

N=8000

Reduction of CV Events with EPA –Intervention Trial

• Randomized, double-blind, parallel group design

• Secondary outcome measures: Incidence of additional CV events, lipid and lipoprotein levels, subgroup analyses such as diabetes, etc.

• Multinational trial

• Anticipated completion 2016

Hx=history; yo=year(s) old. NIH website. http://clinicaltrials.gov/ct2/show/NCT01492361?term=REDUCE-IT&rank=1.

• Men & women ≥45 yo• Prior CHD (70% patients)

or T2DM + ≥1 RF)• Atherogenic dyslipidemia:

– Hx of ↑TC (at LDL-C goal on statin)

– TG 150–500 mg/dL

AMR101=icosapent ethyl

Note: EPA is notFDA approved for TG 200–500 mg/dL

Approximate Levels of EPA and DHA Through Dietary Intake of Fish

100 g ≈ 3.5 oz, or ~¾ cup of flaked fish

Fish EPA plus DHA (mg/100 g eaten)

Salmon Atlantic wild 1840

Salmon Atlantic farmed 2150

Salmon Chinook 1740

Salmon Coho wild 1060

Salmon Coho farmed 1280

Herring Atlantic 2000

Herring Pacific 2130

Mackerel Pacific and jack 1850

Mackerel Atlantic 1200

Mackerel king 400

Halibut Atlantic and Pacific 470

Halibut Greenland 1180

Tuna bluefin 1500

Tuna yellowfin 280

Tuna skipjack 300

Bluefish 990

Pollock Alaskan 120‡

Cod Atlantic 160

Cod Pacific 280

Sablefish (black cod)† 1790

Bass sea 760

Bass freshwater 760

Whitefish 1610

Trout rainbow wild 990

Trout rainbow farmed 1150

*Cooked fish (dry heat) often has less OM-3 FA content than raw fish: 100 g of fish would be ~4 oz, which would be a bit larger than a deck of playing cards. The amount of OM-3 FAs varies considerably in the same type of fish, depending on the environment and location. †Sablefish or “black cod” is not part of the codfish family. ‡Alaskan Pollock is the fish used in many fast-food restaurants, where it is usually battered and fried.Bays HE. Drugs Today (Barc). 2008;44:205-46.

Approximate levels of EPA and DHA in dry-heat cooked fish*

Prescription vs Dietary Supplement OM-3

OM-3 acid ethyl esters

Icosapent ethyl Dietary Supplements

FDA product classification Drug Drug Food

FDA approval Yes Yes No

Ingredients DHA + EPA EPA Variable amounts of DHA + EPA (may include other PUFAs)

Quantity of OM-3 per capsule

1 g 1 g Typically 300 mg – 800 mg EPA & DHATypically 100 – 400 EPA

Capsules/day to achieve 4g OM-3

4 4 Typically 5 – 13 for EPA & DHATypically 10 – 40 EPA

Recommended dose 4 g/day 4 g/day

In patients with CHD: Consume ~1 g of EPA+DHA per day, preferably from oily fish. EPA+DHA supplements could be considered in consultation with the physician.

In patients requiring TG lowering: 2–4 grams of EPA+DHA per day provided as capsules under a physician’s care

When using prescription OM-3 agents to reduce TG levels: 4 grams of OM-3 FAs per day

Tested in clinical trials Yes Yes Not required

Case 1: 62-yo Hispanic Woman with T2DM, no Prior CHD Events, with High TG

Case 1: 62-yo Hispanic Woman with T2DM, No Prior CHD Events, with HTG

Meds: None for lipids, BP, or platelets

Exam: BMI=31 kg/m2, BP=135/95 mm Hg, Waist=36” Non-smoker

Labs:

Fasting glucose 115 mg/dL

A1c 6.2%

TC 200 mg/dL

TG 559 mg/dL

HDL-C 27 mg/dL

LDL-C 118 mg/dL

Non-HDL-C 173 mg/dL

ATP III Treatment Recommendations for Elevated TG

TG (mg/dL)

ATP III Classification

Primary Target of Therapy Treatment Recommendations

150–199 Borderline high LDL-C goal Weight and Physical activity

200–499 High LDL-C goal

Weight and Physical activity

Consider non-HDL-C goal:LDL-C with statin or VLDL-C with niacin

or fibrateSugar/carbs*

≥500 Very high

TGto prevent

acute pancreatitis

Very low fat diet (fat ≤15% total calories)Weight and Physical activityAdd niacin or fibrates(+OM-3 as per FDA indication*)

*Not in ATP III statement.

NCEP ATP III. Circulation 2002;106:3143-421.

9

Case 2: 49-yo Caucasian Man with T2DM, MI, and PCI 2 yrs Ago with Modestly Elevated TG

Michael Miller, MD

Case 2: 49-yo Caucasian Man with T2DM, MI, and PCI 2 yrs Ago with Modestly Elevated TG

Meds: Metformin 1000 mg bid, ASA 81 mg/d, atorvastatin 40 mg/d

Exam: BMI=29 kg/m2, BP=129/82 mm Hg, Waist=41”

LabsA1c 6.5%

TG 248 mg/dL

LDL-C 75 mg/dL

HDL-C 38 mg/dL

Non-HDL-C 139 mg/dL

ASA=aspirin; PCI=percutaneous coronary intervention.

Case 2: 49-yo Caucasian Man with T2DM, MI, and PCI 2 yrs Ago with Modestly Elevated TG

Meds: Metformin 1000 mg bid, ASA 81 mg/d, atorvastatin 40 mg/d

Exam: BMI=29 kg/m2, BP=129/82 mm Hg, Waist=41”

LabsA1c 6.5%

TG 248 mg/dL

LDL-C 75 mg/dL

HDL-C 38 mg/dL

Non-HDL-C 139 mg/dL

Case 2: Treatment Approach

Establish the patient’s risk status:49-yo man, T2DM, previous MI with PCI 2 yrs ago, non-smoker

Risk factor Patient

Gender: Male Yes: Male

Age: >45 years Yes: 49 years

Previous MI Yes

T2DM Yes: T2DM = CHD risk equivalent

MetS: 3 of 5 RFs1. Waist >40”2. Hyperglycemia3. HDL-C <40 mg/dL4. TG >150 mg/dL5. High BP

Yes: MetS (4 of 5)1. Yes, 41”2. Yes3. Yes, 38 mg/dL4. Yes, 248 mg/dL5. No: BP 129/82 mm Hg

This patient is very high risk

Risk status established, set goals for therapy

Residual CVD Risk in Major Statin Trials

4HPS Collaborative Group. Lancet. 2002;360:7-22. 5Shepherd J et al. N Engl J Med. 1995;333:1301-7.6 Downs JR et al. JAMA. 1998;279:1615-22.

14S Group. Lancet. 1994;344:1383-9.2LIPID Study Group. N Engl J Med. 1998;339:1349-57. 3Sacks FM et al. N Engl J Med. 1996;335:1001-9.

N 4444 4159 20,536 6595 66059014

Secondary High Risk Primary

Pa

tie

nts

Ex

pe

rie

nc

ing

M

ajo

r C

HD

E

ve

nts

, % Placebo

Statin19.4

12.310.2

8.75.5 6.8

28.0

15.913.2 11.8

7.910.9

CHD events occur in patients treated with statins

AFCAPS= Air Force Coronary Atherosclerosis Prevention Study; HPS=Heart Protection Study; LIPID= Long-term intervention with pravastatin in ischemic disease; TexCAPS=Texas Coronary Atherosclerosis Prevention Study.

Case 2: Goals for Therapy

Goal Patient Treatment

BP: Age ≥18 years with T2DM: Initiate Rx treatment when SBP is ≥140 mm Hg or DBP is ≥90 mm Hg (JNC8)*

129/82 mm Hg, Not on BP Rx

No treatment needed at this point

LDL-C: <100 mg/dL, optional <70 mg/dL

75 mg/dLIs relatively low LDL-C misleading? Why? What to do?

Non-HDL-C: <130 (<100 optional)

139 mg/dLNon-HDL-C high on atorva 40! Needs non-HDL-C statin adjunct

TG: <150 mg/dL (target) 248 mg/dLAddress 2o factorsLikely needs TG statin adjunct

HDL-C >40 mg/dL (target) 38 mg/dL May need HDL-C statin adjunct

A1c: <6.5% 6.5% None: He is at goal on metformin

Waist: <40”BMI: 18.5–24.9 kg/m2

(Obese: >30 kg/m2)

41”29 kg/m2

Physical activity: 30–60 minutes of daily moderate aerobic activityDiet: ↓sugars, calories & alcohol

*James PA et al. JAMA. 2013; Dec 18. [Epub ahead of print]. DBP=diastolic BP; JNC=Joint National Committee.

10

Status of the ABCs of Risk Management

Centers for Disease Control (CDC). MMWR Morb Mortal Wkly Rep. 2011;60:1248-51.

Percent Compliant

AspirinPeople at risk of CV events who are taking aspirin 47%

Blood pressurePeople with HTN who have adequately controlled BP 46%

CholesterolPeople with cholesterol who are effectively managed 33%

SmokingPeople trying to quit smoking who get help 23%

Conclusions

• Assess risk factor profile to determine treatment goals

• In the setting of elevated TGs, LDL-C may be misleadingly low

• Non-HDL-C goal is a good lipid target to use, especially in patients with TG >200 mg/dL

• Compliance is always an important treatment issue

Question & Answer