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2016 Lipid Update: What’s HOT? And, what’s NOT!

Speaker has no relationship to disclose.

Amelie Hollier, DNP, FNP-BC, FAANP Advanced Practice Education Associates

Objectives • Review 2013 evidence-based guidelines for management of dyslipidemia • Review medication/classes used to manage patients who have dyslipidemia • Develop strategies for dyslipidemia management

2013 Lipid Guidelines:

What happened to my LDL targets? Where do I go from here?

4 Steps to Understanding the 2013 ACC/AHA Guidelines

The ACC/AHA 2013 Guidelines • Shift the way we think about treatment of dyslipidemia • The GOAL is to reduce CV risks using interventions that are evidence-

based

• • • •

New Risk Calculator Who profits from taking a statin? What number? What statin? “Other” issues

Stone N J, Robins on J, Lichtens tein AH, et al. 2013 ACC/ AHA G uideline on the Treatment of Blood Choles terol to Reduce Atheros clerotic Cardiovas cular Ris k in Adults : A Report of the American College of Cardiology/ American Heart As s ociation Tas k Force on Practice G uidelines . Circulation 2013.

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Framingham Risk Calculator • Framingham used only whites, less precise in patients with DM • New calculator more generalizable: race and gender specific • New calculator includes global CV disease outcomes (nonfatal MI, CHD death, fatal/nonfatal stroke) vs CHD death and nonfatal MI • Use every 4-6 years in ages 40-79 without established ASCVD Stone N J, Robins on J, Lichtens tein AH, et al. 2013 ACC/ AHA G uideline on the Treatment of Blood Choles terol to Reduce Atheros clerotic Cardiovas cular Ris k in Adults : A Report of the American College of Cardiology/American Heart As s ociation Task Force on Practice G uidelines . Circulation 2013.

New Pooled Cohort Equations CV Risk Calculator • Calculates 10 year risk of MI or stroke • Males, females Caucasian, AA, 40-79 years with or without DM • May underestimate risk for 20-59 year olds

Pooled Cohort Equations CV Risk Calculator • http://my.americanheart.org/cvriskca lculator (spreadsheet) • Many available for free download for Apple and for Android products

Stone N J, Robins on J, Lichtens tein AH, et al. 2013 ACC/ AHA G uideline on the Treatment of Blood Choles terol to Reduce Atheros clerotic Cardiovas cular Ris k in Adults : A Report of the American College of Cardiology/American Heart As s ociation Task Force on Practice G uidelines . Circulation 2013.

Pooled Cohort Equations CV Risk Calculator • Big CRITICISM of risk calculator is that it OVER/UNDERESTIMATES patient risks (compared to Framingham)

• May overestimate risk for >75 year olds

One more thing: Pooled Cohort Equations CV Risk Calculator • Not intended for use with statin-treated cholesterol (use pre-treatment cholesterol value) • If pre-treatment cholesterol unknown, shoot for LDL < 100 mg/dL

Stone N J, Robins on JG , Lichtens tein AH, et al. Treatment of blood choles terol to reduce atherosclerotic cardiovas cular dis eas e risk in adults : s ynops is of the 2013 American College of Cardiology/American Heart As s ociation choles terol guideline. Ann Intern Med 2014;160:339-43.

Don’t like the “new” Risk Calculator? Risk Calculator

Web Access

Basic Descriptors

Framingham Coronary Heart Disease 10-year Risk

http://www.framinghamheartstudy.org/ Calculates 10 yr risk of CHD risk-functions/coronary-heartWhites 30-74 without CHD disease/10-year-risk.php Can use in AA, Hispanic females

Framingham General Cardiovascular Disease 10-year Risk

http://www.framinghamheartstudy.org/ Calculates 10 yr risk CVD risk-functions/cardiovascularWhites 30-74 years without CVD disease/10-year-risk.php at baseline Separate calculators for men and women

Reynolds Risk score

http://www.reynoldsriskscore.org

American Diabetes Association’s Diabetes My Health Advisor risk assessment tool

http://www.diabetes.org/living-withdiabetes/complications/diabetes-phd/

Calculates 10 yr risk of major CV event For healthy patients without DM 45-80 y/o Separate calculators for men and women Based on WHI, Physician’s health study II Calculates 10 yr risk of MI or stroke; 8 yr risk of DM, complications

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4 Steps to Understanding the New Guidelines

Calculator Apps for Smartphones Calculate (http://www.qxmd.com/specialty/medicine/cardiologymedical-apps-iphone-blackberry-android) includes Framingham and Reynolds for iPhone, iPod Touch, iPad, Blackberry, and Android (free)

The ACC/AHA 2013 GUIDELINES

• • • •

New Risk Calculator Who profits from taking a statin? What number? What statin? “Other” issues

The ACC/AHA 2013 GUIDELINES

4 Groups Benefit from a Statin

4 Groups Benefit from a Statin

1. History of CHD or stroke (secondary prevention of ASCVD) 2. Patients with LDL >190 mg/dL

3. DM (no evidence of ASCVD), 40-75 years old with LDL 70-189 mg/dL 4. Patients (without evidence of ASCVD or DM) with LDL 70-189 mg/dL PLUS estimated 10 year risk of ASCVD > 7.5%

“High Risk Groups”

“Moderate Risk Groups”

ASCVD=atherosclerotic cardiovascular disease Stone N J, Robins on J, Lichtens tein AH, et al. 2013 ACC/ AHA G uideline on the Treatment of Blood Choles terol to Reduce Atheros clerotic Cardiovas cular Ris k in Adults : A Report of the American College of Cardiology/American Heart As s ociation Tas k Force on Practice G uidelines . Circulation 2013.

Case 1: Mr. Boudreaux 40 year old white male, non-smoker, no DM, systolic BP =120 Father died of AMI 45 years old Total Cholesterol: 310 mg/dL HDL: 50 mg/dL LDL: 180 mg/dL

Calculated 10 yr risk = 2.4%

Circulation. 2013 N ovStone N J, Robins on J, Lichtens tein AH, et al. 2013 ACC/AHA G uideline on the Treatment of Blood Choles terol to Reduce Atheros clerotic Cardiovas cular Ris k in Adults : A Report of the American College of Cardiology/ American Heart As s ociation Tas k Force on Practice Guidelines . Circulation 2013.

What if your patient doesn’t fit into one of these 4 groups? 40 year old white male, nonsmoker, no DM, systolic BP =120 Father died of AMI 45 years old Total Cholesterol: 310 mg/dL HDL: 50 mg/dL LDL: 180 mg/dL Calculated 10 yr risk = 2.4%

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What if your patient doesn’t fit into this group? “Additional factors can be taken into consideration” • • • • • • •

LDL > 160 mg/dL or genetic hyperlipidemia ASCVD in male FDR prior to age 55 years ASCVD in female FDR prior to 65 years hsCRP > 2 mg/dL ABI < 0.9 Elevated lifetime risk of ASCVD Elevated calcium score

Guidelines Controversy

Abandonment of the LDL Targets (Goals: LDL < 100 mg/dL LDL < 70 mg/dL)

• Randomized, controlled clinical trials demonstrated benefit using specific statin doses---NOT achieving LDL targets • Recommendation: Continue to measure LDL levels but don’t target specific numbers

“High Risk” Groups

Profit from 50% or > reduction in LDL with statin

1. Secondary prevention in adults < 75 years 2. Primary prevention in adults with LDL > 190 mg/dL 3. Primary prevention in adults 40-75 years with LDL 70-189 mg/dL PLUS estimated ASCVS risk of > 7.5% 4. Primary prevention in DM 40-75 years of age with LDL 70-189 mg/dL PLUS estimated ASCVD risk of > 7.5% (Level C)

4 Steps to Understanding the New Guidelines • • • •

New Risk Calculator Who profits from taking a statin? What number? What statin? “Other” issues

What Drug Class to Reduce Risks? • Statins are FIRST choice! • Statins are ONLY class to demonstrate reductions in mortality in primary and secondary prevention • Non-statins?

Statins for “High Risk” Groups Recommendation: Need LDL reduction of 50% or greater, use: Statin Atorvastatin Rosuvastatin

Dosage in mg 40* , 80 20, 40

Generic Yes No

* 40 mg if 80 mg not tolerated

Level C=cons ens us or expert opinion

Stone N J, Robins on J, Lichtens tein AH, et al. 2013 ACC/ AHA G uideline on the Treatment of Blood Choles terol to Reduce Atheros clerotic Cardiovas cular Ris k in Adults : A Report of the American College of Cardiology/American Heart As s ociation Task Force on Practice G uidelines . Circulation 2013.

Stone N J, Robins on J, Lichtens tein AH, et al. 2013 ACC/ AHA G uideline on the Treatment of Blood Choles terol to Reduce Atheros clerotic Cardiovas cular Ris k in Adults : A Report of the American College of Cardiology/American Heart As s ociation Task Force on Practice G uidelines . Circulation 2013.

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Statin CYP 450 Effect LDL Decrease

Atorvastatin

Rosuvastatin

50-60% 40-80mg

50-63% 20-40 mg

CYP 450 Effect 3A4 enzymes

Not significantly metabolized by CYP 450

“Moderate Risk” Groups Profit from 30-49% reduction in LDL with statin

1. Secondary prevention in adults > 75 years old 2. Primary prevention in adults 40-75 years with LDL 70-189 mg/dL PLUS estimated ASCVS risk of > 7.5% (could use high dose) 3. Primary prevention in DM 40-75 years of age with LDL 70-189 mg/dL PLUS estimated ASCVD risk of < 7.5% (Level A)

Level A=High quality RCT, high quality meta-analysis

Stone N J, Robins on J, Lichtens tein AH, et al. 2013 ACC/ AHA G uideline on the Treatment of Blood Choles terol to Reduce Atheros clerotic Cardiovas cular Ris k in Adults : A Report of the American College of Cardiology/American Heart As s ociation Task Force on Practice G uidelines . Circulation 2013.

“Moderate Risk” Groups Profit from 30-49% reduction in LDL with statin Statin Atorvastatin Fluvastatin Lovastatin Pitavastatin Pravastatin Rosuvastatin Simvastatin

Dosage in mg 10, 20 40 BID; 80 daily 40 2, 4 40, 80 5, 10 20, 40

Generic Yes Yes Yes No Yes No Yes

Circulation. 2013 Nov.

ACC/AHA Guidelines Statin Name

% LDL lowering

Level of Intensity

Atorvastatin

35-60%

HIGH (> 50% LDL

Rosuvastatin

45-63%

HIGH

Simvastatin

26-41%

Moderate (30-49% LDL

Pitavastatin

29-45%

Moderate

Pravastatin

22-37%

Moderate

Lovastatin

21-42%

Moderate

lowering capacity)

lowering capacity)

If a patient is intolerant of a moderate or high dose of a statin,

If a patient is intolerant of a moderate or high dose of a statin,

OK to use a low dose statin.

OK to use a low dose statin.

Take Home Point: Get the patient on a statin!

What if they are diabetic?

Stone N J, Robins on J, Lichtens tein AH, et al. 2013 ACC/ AHA G uideline on the Treatment of Blood Choles terol to Reduce Atheros clerotic Cardiovas cular Ris k in Adults : A Report of the American College of Cardiology/American Heart As s ociation Tas k Force on Practice G uidelines . Circulation 2013.

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4 Steps to Understanding the New Guidelines

2016 ADA Section 8 Consider adding ezetimibe to a moderate intensity statin to provide additional CV benefits for patients with diabetes who have had recent acute coronary syndrome with LDL > 50 mg/dl or who cannot tolerate high intensity statin therapy.

• • • •

New Risk Calculator Who profits from taking a statin? What number? What statin? Amelie’s “Other” issues

Evidence Level: A

American Diabetes As s ociation. Clas s ification and diagnos is of diabetes . S ec. 8. In Standards of Medical Care in Diabetes -2016. Diabetes Care 2016;39(Suppl. 1).

We KNOW that they work!!!!

Statin Efficacy

“Other Issues” with Statins

Statin Name

• • • • • •

Efficacy vs Cost Drug Interactions: CYP 450 Hepatotoxicity Tolerability New onset Diabetes Statin Alternatives

Statin Cost v. Efficacy Statin Name

% LDL lowering

Cost

Atorvastatin

35-60%

10 mg: $7.08 (generic)/ $10.17 (generic)

Rosuvastatin

45-63%

Simvastatin

26-41%

5 mg: $171.33/$10.45 (generic-Canada) Generic in 2016 20 mg: $ rhabdo • Myalgias can occur WITHOUT elevations is serum creatine kinase • Rhabdo UNCOMMON! (75-80 years Use of meds/food that increase statin levels • Personal or family history of statin or myopathy • Multiple disease states or polypharmacy • • • • • • • •

Stroes ES, Thomps on PD, Cors ini A, et al. Statin as sociated muscle symptoms : impact on s tatin therapy-European Atheros cleros is Society cons ensus panel s tatement of ass ess ment etiology and management. Eur Heart J 2015;36:1012-22.

Before Starting a Statin Ask about any pre-existing muscle symptoms PRIOR to starting statin so not discontinued unnecessarily! 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.

Before Starting a Statin • Set patient expectations if myalgias occur

Stroes ES, Thomps on PD, Cors ini A, et al. Statin as s ociated mus cle s ymptoms : impact on s tatin therapy-European Atheros cleros is Society cons ens us panel s tatement of as s es s ment etiology and management. Eur Heart J 2015;36:1012-22.

Before Starting a Statin

Consider

• Screen for drug interactions • Ensure that dose is appropriate for renal function

• CK prior to starting ONLY IF RISK FACTORS PRESENT! • Exercise can elevate CK

Stone N J, Robins on J, Lichtens tein AH, et al. 2013 ACC/ AHA G uideline on the Treatment of Blood Choles terol to Reduce Atheros clerotic Cardiovas cular Ris k in Adults : A Report of the American College of Cardiology/ American Heart As s ociation Tas k Force on Practice G uidelines . Circulation 2013.

Stroes ES, Thomps on PD, Cors ini A, et al. Statin as s ociated mus cle s ymptoms : impact on s tatin therapy-European Atheros cleros is Society cons ens us panel s tatement of as s es s ment etiology and management. Eur Heart J 2015;36:1012-22.

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ACC/AHA guidelines, NLA panel, and European consensus panel

If muscle pain occurs…what next? Stroes ES, Thomps on PD, Cors ini A, et al. Statin as s ociated mus cle s ymptoms : impact on s tatin therapy-European Atheros cleros is Society cons ens us panel s tatement of as s es s ment etiology and management. Eur Heart J 2015;36:1012-22.

General Muscle Complaints

Hold statin: • For 2-4 weeks if intolerable symptoms, weakness, or CK > 3 times ULN (upper limits of normal) • Evaluate strength by physical exam

General Complaints • Consider other illnesses/conditions: hypothyroidism, vitamin D deficiency, rheumatologic or musculoskeletal disease, exercise, steroid myopathy, antipsychotics, immunosuppressants, bisphosphonates, EtOH or drug abuse, drug or food interactions (fibrates, macrolides, protease inhibitors, etc.) • If illness found to be the cause, treat, restart the statin at the same dose

Consider Rhabdo if…. Rhabdo 30 Journal of American College of Cardiology, Jan. 2013

Type 2 Diabetes No increased risk of NOD in patients with low risk of DM

What if you can’t reach % reduction with statin? • Reinforce lifestyle changes • Look for a secondary cause

Journal of American College of Cardiology, Jan. 2013

“Other Issues” with Statins • • • • •

Efficacy vs Cost Drug Interactions: CYP 450/Hepatotoxicity Tolerability New onset Diabetes Statin Alternatives

What if you can’t reach % reduction with statin? Non-Statins??? “Don’t routinely use non-statins” No proof that non-statins improve CV outcomes when added to a statin. Sto n e NJ, R o b i n so n J, Li ch ten stei n AH, et al . 2 0 1 3 AC C /AHA Gu i d el i n e o n th e Treatmen t o f B l o o d C h o l estero l to R ed u ce Ath ero scl ero ti c C ard i o vascu l ar R i sk i n Ad u l ts: A R ep o rt o f th e Ameri can C o l l ege o f C ard i o l o gy/Ameri can Heart Asso ci ati o n Task Fo rce o n P racti ce Gu i d el i n es. C i rcu l ati o n 2013.

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Non-Statins??? Consider in high risk patients who don’t get percent LDL lowering from statin alone

No proof that non-statins improve CV outcomes when added to a statin.

The Newest Drug Class: PCSK9 Inhibitors

• Proprotein • Convertase • Subtilisin • Kexin type 9 • Monoclonal antibody

Cros s ey, E. Amar, M.J, Samps on, M. Peabody, J. Schiller, JT, Chackerian, B. Remaley, A.T. (2015). Vaccine. A choles terol lowering VLP vaccine that targets PCSK9. Oct 26;33(43):5747-55. doi: 10.1016/ j.vaccine. Vaccine.2015.09.044. Epub 2015 Sep 26.

PCSK9: Background

• PCSK9 is an enzyme in the liver, some people make A LOT! • Causes degradation of LDL receptors • Without LDL receptors, LDL “roams” the blood stream

PCSK9 Inhibitors • PCSK9 Inhibitors PREVENT the enzyme from binding to the LDL receptors • And….they wreck your receptor sites! • If the enzyme can’t bind, then there are lots of LDL receptors to bind LDL and keep it out of the blood stream! Cros s ey, E. Amar, M.J, Samps on, M. Peabody, J. Schiller, JT, Chackerian, B. Remaley, A.T. (2015). Vaccine. A choles terol lowering VLP vaccine that targets PCSK9. Oct 26;33(43):5747-55. doi: 10.1016/ j.vaccine. Vaccine.2015.09.044. Epub 2015 Sep 26.

PCSK9 Inhibitors • Praluent (alirocumab) • Repatha (evolocumab) • $10,000-$14,000/year • Subq injection every 2 weeks Cros s ey, E. Amar, M.J, Samps on, M. Peabody, J. Schiller, JT, Chackerian, B. Remaley, A.T. (2015). Vaccine. A choles terol lowering VLP vaccine that targets PCSK9. Oct 26;33(43):5747-55. doi: 10.1016/ j.vaccine. Vaccine.2015.09.044. Epub 2015 Sep 26.

PCSK9 Inhibitors: For Whom? • Familial hypercholesterolemia ) 1 in 200 people) • Reduce LDL 60% • Statins remain first line • Could be a statin “add on” • Myalgia rates: 3-5% (Statins: up to 30%) Cros s ey, E. Amar, M.J, Samps on, M. Peabody, J. Schiller, JT, Chackerian, B. Remaley, A.T. (2015). Vaccine. A choles terol lowering VLP vaccine that targets PCSK9. Oct 26;33(43):5747-55. doi: 10.1016/ j.vaccine. Vaccine.2015.09.044. Epub 2015 Sep 26.

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Ezetimibe (Zetia)

Ezetimibe

Cholesterol absorption inhibitors

ENHANCE Trial

• Can be combined with a statin • ENHANCE trial: Reductions in LDL and increases in HDL, BUT……..

• Simvastatin plus ezetimibe vs. simvastatin • No change in primary outcome (carotid intima-media thickness)

IMPROVE-IT Trial IMProved Reduction of Outcomes: Vytorin Efficacy International Trial 18,000 subjects with MI or chest pain given either statin alone or statin + ezetimibe At 6 years: 34.7% with statin alone had MI, stroke, hospitalization or revascularization compared to 32.7% with statin + ezetimibe Cannon CP, et al.; IMPROVE-IT Investigators. IMPROVE-IT trial: a comparison of ezetimibe/simvastatin versus simvastatin monotherapy on cardiovascular outcomes after acute coronary syndromes. Presented at: American Heart Association Conference; November 15-19, 2014; Chicago, IL. LBCT-02.

IMPROVE-IT Trial Very specific population (Post MI, chest pain) Small population (18,000 subjects) 6 years (long time to realize benefit) (50 treated to prevent MI, stroke at 6 years; 70 treated at 5 years)

IMPROVE-IT Trial IMProved Reduction of Outcomes: Vytorin Efficacy International Trial Ezetimibe (Zetia) Ezetimibe + simavastatin (Vytorin) • 2% absolute difference • Argument: lower LDL is better; non-statin was beneficial Cannon CP, et al.; IMPROVE-IT Investigators. IMPROVE-IT trial: a comparison of ezetimibe/simvastatin versus simvastatin monotherapy on cardiovascular outcomes after acute coronary syndromes. Presented at: American Heart Association Conference; November 15-19, 2014; Chicago, IL. LBCT-02.

Cost of Ezetimibe • $7 per day simvastatin plus ezetimibe • .25 generic statin • Ezetimibe generic in 2016

Cannon CP, et al.; IMPROVE-IT Investigators. IMPROVE-IT trial: a comparison of ezetimibe/simvastatin versus simvastatin monotherapy on cardiovascular outcomes after acute coronary syndromes. Presented at: American Heart Association Conference; November 15-19, 2014; Chicago, IL. LBCT-02.

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2016 ADA Section 8

Fatty Fish

Consider adding ezetimibe to a moderate intensity statin to provide additional CV benefits for patients with diabetes who have had recent acute coronary syndrome with LDL > 50 mg/dl or who cannot tolerate high intensity statin therapy.

• 3-4 weekly meals increased the size of HDL particles • Larger particles = more CV protection • Large HDL particles more efficient at removing extra cholesterol from artery walls

Evidence Level: A

American Diabetes As s ociation. Clas s ification and diagnos is of diabetes . S ec. 8. In Standards of Medical Care in Diabetes -2016. Diabetes Care 2016;39(Suppl. 1).

Rx Strength Fish Oil Prescription strength Omega-3s (Lovaza® formerly Omacor®)

• US FDA limited approval to treatment of severe hypertriglyceridemia (>500 mg/dL); will increase LDL-C levels • 1g provides 465 mg EPA, 375 mg DHA • 4g per day PO div once or twice • Linear response to dose

Hypertriglyceridemia How about the lipids? Lab

Results

Normal Range

A1C BUN, Cr, eGFR Potassium

7.9% 21, 1.6, 72 72 ml/min 4.3 mEq/L

4.8-5.6% 8-25 meq/L, 0.5-1.5 meq/L >60 ml/min 3.5-5.1 meq/L

Total Cholesterol

210 mg/dL

40 mg/dL

Glucose

165 mg/dL

70-99 mg/dL

Triglycerides PSA

423 mg/dL 1.6 ng/dL

< 150 mg/dL < 2.5 ng/dL

Rx Strength Fish Oil Secondary effects Omega-3 ethyl esters: • Increase HDLs 9.1% • Raise LDLs up to 44.5% • Safe for use with a statin • Lowers the proportion of small dense LDLs (sdLDL)

Hypertriglyceridemia Associated with: • Low levels of HDL • Presence of small, dense LDL particles • Insulin resistance (A1C =5.9%) • Increases in coaguability and viscosity of blood

Circulation 1999 Jun 8;99(22):2901-7.

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Low HDL: Insulin Resistance

Insulin Resistance

• Low HDL may be a component of insulin resistance

• There is “discordance” between LDL cholesterol and LDL particle concentration/apolipoprotein B in patients with Insulin Resistance!

Example: Insulin Resistance

Example: Insulin Resistance

• LDL particles REMODEL as insulin resistance worsens • LDL cholesterol levels do not reflect the number of LDL particles in a patient with insulin resistance

• T2DM: LDL < 100 mg/dL, 66% have excess LDL particles • T2DM: LDL < 70 mg/dL, 41% have excess LDL particles • We can measure particle concentration!

Is LDL < 100 mg/dL good enough goal for a diabetic?

Hypertriglyceridemia

Hypertriglyceridemia

When Trigs > 500 mg/dL

Management

• Goal is to prevent pancreatitis

• Trigs 150-199: Weight reduction, increased physical activity • Trigs 200-499: Attack LDL first, then trigs

by lowering trigs • Once trigs < 500 mg/dL, address LDL goal! • Reduction of cardiovascular risks!

• Trigs >500: prevent pancreatitis first with non-pharm plus meds. When below 500, address LDL!

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Lifestyle Changes • Maximize Non-pharm Management

What Diseases? Associated with Hypertriglyceridemia

Diabetes, metabolic syndrome, nephrotic syndrome, Cushing’s, hypothyroidism, cirrhosis, alcoholism

• Weight loss in obese patients • Aerobic exercise • Avoidance of concentrated sugars • Strict glycemic control in diabetics (first line) • Avoidance of alcohol

Hypertriglyceridemia

What Medications? Associated with Hypertriglyceridemia

Estrogen (probably not transdermal), tamoxifen, high dose beta blockers, steroids, retinoid therapy, HIV regimens

Fibric Acids • Gemfibrozil • Fenofibrate

April 18, 2016 FDA withdraws indications for: • Niacin ER tabs • Fenofibric acid delayed release caps For co-administration with statins

April 18, 2016 • • • •

Meds Effected Niaspan Trilipix Advicor Simcor

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What about Niacin?

Is Niacin Dead???

Niacin = B3 = nicotinic acid • Increases HDL-C • Substantially decreases triglycerides • Modestly decreases LDL-C • Causes lots of flushing!!!!

2014: HPS2-Thrive Study (Heart Protection Study 2, Treatment of HDL to reduce vascular events) • 25,000 adults aged 50-80 years • All had some clinical manifestation of CV disease (CAD, MI, PAD,DM plus CVD) • All got a statin, some also got niacin, some got placebo • Niacin plus statin had better lipid profiles

The HPS2-THRIVE Collaborative Group. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med. 2014;371:203-212.

The HPS2-THRIVE Collaborative Group. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med. 2014;371:203-212.

What’s Hot?

Is Niacin Dead???

Lipid Lowering Agent

HPS2-Thrive Study: BUT

Statins PCSK9 inhibitors Ezetimibe Niacin Fibrates Fish Oil

• No reduction in major CV events • More myopathy, bleeding (GI bleeding, intracranial bleeding, other sites) • More new onset diabetes • ??? Serious infections The HPS2-THRIVE Collaborative Group. Effects of extended-release niacin with laropiprant in high-risk patients. N Engl J Med. 2014;371:203-212.

Thank you!

References • • • • • • • • • •

To Reach me: Amelie Hollier, DNP, FNP-BC, FAANP Advanced Practice Education Associates Lafayette, LA [email protected]

Hot? Yes! Probably Warm No No No

Sto n e NJ, R o b i n so n J, Li ch ten stei n AH, et al . 2 01 3 A C C /AHA G u i del i n e o n the Treatmen t o f B l o o d C h o lestero l to R ed u ce Ath ero scl ero ti c C ard i o vascu l ar R i sk i n Ad u l ts: A R ep o rt of th e Ameri can C o l l ege o f C ard i o l o gy/Ameri can Heart Asso ci ati o n Task Fo rce o n P ractice Gu i d el i n es. C i rcu l ati o n 2 0 1 3 . Navarese, EP . K o l o d zi ejczak, M ., Sch u l ze, V., et al . Effects o f P ro p ro tei n C o nvertase Su b ti l i si n /K exi n Typ e 9 An ti b o d i es i n Ad u lts wi th Hyp erch o l estero l emi a: A Systemati c R evi ew an d M eta-an al ysi s. An n In tern M ed 2 0 1 5 ; 1 63 :40 . An d erso n TJ, Grego i re J, Hegel e R A, et al . 2 0 1 2 u p date o f th e C an ad i an C ard i o vascu l ar So ci ety gu i d el i n es fo r th e d i agn o si s an d treatmen t o f d ysl i p i d emi a fo r th e p reven ti o n o f card i o vascu l ar d i sease i n th e ad u l t. C an J C ard i o l 2 01 3 ; 2 9 1 : 5 1. B o ekh o l d t SM , Arsen au l t B J, M o ra S, et al . Asso ci ati o n o f LDL ch o l estero l , n o n-HDL ch o l estero l , an d ap o il p o pro tei n B l evel s wi th ri sk o f card i o vascul ar even ts amo n g p ati en ts treated wi th stati n : a meta-an al ysi s. JAM A 2 0 1 2 ; 30 7 :13 02 . M i l l s EJ, O’R egan C , Eyawo O, et al . In ten si ve stati n th erap y co mp ared wi th mo d erate d o si n g fo r p reven ti o n o f card i o vascu l ar even ts: a meta-an al ysi s o f >4 0 ,0 0 0 p ati en ts. Eu r Heart J 2 0 1 1 ; 32 :14 0 9. Stro es E, C o l q u h o u n D, Su l l i van D, et al . An ti -P CSK 9 an ti bo d y effecti vel y l o wers ch o l estero l i n p ati en ts wi th stati n i n to l eran ce. J Am C o l l C ard i o l 2 0 1 4 ;6 3 :2 5 41 -8 .

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FDA. FDA ad vi so ry co mmi ttee b ri efi n g d o cu men t P ra l u en t. Ju n e 9 , 2 0 15 . h ttp ://www.fd a.go v/d o wn l o ad s/Ad vi so ryC o mmi ttees/C o mmi tteesM e eti n gM ate ri al s/ Dru gs/En d o cri n o l o gi can d M etab o l i cDru gsAd vi so ryC o mmi ttee/UC M 4 4 9 8 6 7 .p d f. (Accessed Ju l y 1 0 , 2 0 1 5 ).

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Navarese SP , K o l o d zi ejczak M , Sch u l ze V, et al . Effects o f p ro p ro tei n co n vertase su b ti l i si n /kexi n typ e 9 an ti b o d i es i n ad u l ts wi th h yp erch o l estero l emi a. An n In tern M ed 2 0 1 5;1 63 :4 0-5 1.

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B l o m DJ, Hal a T, B o l o gn ese M , et al . A 5 2 -week p l aceb o -co n tro l l ed tri al o f evo l o cu mab i n h yp erl i p i d emi a. N En g l J M ed 2 01 4;3 7 0:1 80 9 -19 .

•

FDA. FDA B ri efi n g d o cu men t R ep a th a . Ju n e 1 0 , 2 0 15 . http ://www.fd a.go v/d o wn l o ad s/Ad vi so ryC o mmi ttees/C o mmi tteesM eeti n gM ateri al s/ Dru gs/En d o cri n o l o gi can d M etab o l i cDru gsAd vi so ryC o mmi ttee/UC M 4 5 0 0 7 2 .p d f. (Accessed Ju l y 1 0 , 2 0 1 5 ).

•

R o b i n so n JG, Farn i er M , K remp f M , et al . Effi cacy an d safety o f al i ro cu mab i n red u ci n g l i p i d s an d card i o vascu l ar even ts. N En g l J M ed 2 0 1 5;3 72 :148999.

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