Complicated Dyslipidemia: Beyond First Line Therapy · Managing the Complicated Dyslipidemia Patient: Beyond First-Line Therapy Patrick Curtin, ... Civeira et al. J Clin Lipidol

1

Managing the Complicated

Dyslipidemia Patient:

Beyond First-Line Therapy

Patrick Curtin, PharmD, BCPS

Clinical Coordinator Overlook Medical Center

Summit, NJ

Faculty Information

Presenter:


Clinical Coordinator

Overlook Medical Center

Summit, NJ

Moderator:

David Heckard

Senior Director of Education

Pharmacy Times Office of CPE

Plainsboro, NJ

Disclosures

Patrick Curtin, PharmD, BCPS, has no financial relationships with commercial interests to disclose.

Pharmacy Times Office of Continuing Professional Education Planning Staff—Judy V. Lum, MPA, Elena Beyzarov, PharmD, David Heckard, and Donna W. Fausak—have no financial relationships with commercial interests to disclose.

PTOCPE uses an anonymous peer reviewer as part of content validation and conflict resolution. The peer reviewer has no relevant financial relationships with commercial interests to disclose.

The contents of this webinar may include information regarding the use of products that may be inconsistent with or outside the approved labeling for these products in the United States. Pharmacists should note that the use of these products outside current approved labeling is considered experimental and are advised to consult prescribing information for these products.

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concerning this webinar to:

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Learning Objectives

Review current national guidelines on management of dyslipidemia and discuss emerging lipid goals

Describe the complicated dyslipidemia patient, focusing on refractory familial hyperlipidemia and statin intolerance

Examine strategies for achieving goal lipid levels in patients with familial hyperlipidemia

Discuss clinical aspects and mechanisms of statin-associated adverse effects and strategies for managing statin intolerance

Outline counseling strategies to optimize patient outcomes in management of dyslipidemia

Managing the Complicated

Dyslipidemia Patient:

Beyond First-Line Therapy


Clinical Coordinator Overlook Medical Center

Summit, NJ

2

Initial Goals for CHD Risk Reduction

Identify Cardiovascular Risk

Patient Risk Factors

Smoking

Hypertension

HDL<40 mg/dL

Family history of premature CHD (1st-degree relative with CHD in male <55 y or female <65 y),

Age (male ≥45 y, female ≥55 y)

Define cholesterol goals

Optimize non-drug therapy/modify risk factors

Physical activity

Diet

Smoking cessation

Jellinger et al. Endocr Pract. 2012;18(suppl 1):1-78

Patient Counseling Point

Counsel patient on risk (Framingham Heart Score, Reynolds Score)

35-year-old male smoker, TC 230 mg/dL,

HDL 45 mg/dL with no other comorbidities

Framingham Score: 10% 1% (if quit smoking)

55-year-old male smoker, TC 220 mg/dL,

HDL 40 mg/dL with HTN (SBP 150/95)

Framingham Score: 26% 9% if patient quits smoking, controls blood pressure, and lowers TC to 190 mg/dL

http://hp2010.nhlbihin.net/atpiii/calculator.asp

American Academy of Clinical

Endocrinologists (AACE): 2012 LDL-C Goals

(mg/dL)

HDL-C Classifications

(mg/dL)

Triglycerides

(mg/dL)

High-risk: Established CVD or DM

+ 1 risk factor:

<100 or 70 (optional)

High-risk:

<40 (men)

<50 (women)

High-risk:

200-499*(high)

≥ 500 (very high)

Moderately high-risk: ≥2 risk

factors and 10-year risk >20% or

CHD equivalent

<100

Borderline:

40-59 (men)

50-59 (women)

Borderline:

150-199

Moderately high-risk: ≥2 risk

factors and 10-year risk ≤20%:

<130

Optimal:

≥ 60 (negative risk

factor)

Optimal:

<150

Low-risk: ≤1 risk factors:

<160

Jellinger et al. Endocr Pract. 2012;18(suppl 1):1-78

*Patients with triglycerides of 200-499 mg/dL should have a non-HDL goal 30 mg/dL higher than the LDL goal.

Cornerstone of Drug

Therapy

STATINS

Number Needed to

Treat 24 42 91 63 95

Mean baseline LDL (mg/dL) 150 192 134 118 108

10.9%

7.9%

3.0%

4.6%

2.8%

6.8% 5.5%

1.9% 3.0%

1.6%

0%

2%

4%

6%

8%

10%

12%

Percentage of Major

CHD Events

Placebo Statin

Efficacy of Statins for Primary Prevention

JAMA. 1998;279:1615-1622.

N Engl J Med. 1995;333:1301-1307.

Lancet. 2003;361:1149-1158.

Lancet. 2004;364:685-696.

N Engl J Med. 2008;359:2195-2207.

28.0%

13.2%

15.9%

11.8%

19.4%

10.2% 12.3%

8.7%

0%

5%

10%

15%

20%

25%

30%

4S Care Lipid HPS

Percentage of Major

CHD Events

Placebo Statin

Number Needed to

Treat 11 33 28 32

Mean Baseline LDL (mg/dL) 190 139 150 129

Efficacy of Statins for Secondary

Prevention

Lancet. 1994;344:1383-1389.

N Engl J Med. 1996;335:1001-1009.

N Engl J Med. 1998;339:1349-1357.

Lancet. 2002;360:7-22.

3

Intensive LDL Lowering in Secondary

Prevention

Treatment

Regimens

Atorva 80 mg

Prava 40 mg

Simva 80 mg

Simva 20 mg

Atorva 80 mg

Atorva 20 mg

Atorva 80 mg

Atorva 10 mg

Mean LDL achieved

(mg/dL) 62 vs 95 66 vs 81 80 vs 100 77 vs 101

26.3%

16.7%

10.4% 10.9%

22.4%

14.4%

9.3% 8.7%

0%

5%

10%

15%

20%

25%

30%

PROVE-IT A to Z IDEAL TNT

Percentage of Major CHD

Events

Low Dose Statin

High Dose Statin

P=0.14

P=0.07

N Engl J Med. 2004;350:1495-504.

JAMA. 2004;292:1307-1316.

JAMA. 2005;294:2437-2445.

N Engl J Med. 2005;352.

LDL Reduction with Statins

Statin LDL-C Reduction

Rosuvastatin 45%-55%

Atorvastatin 37%-51%

Simvastatin 28%-46%

Lovastatin 29%-48%

Pravastatin 20%-30%

Fluvastatin 17%-23%

Jones et al. Am J Cardiol. 2003;92(2):152-160.

What do we do after statins?

ASSESS COMPLIANCE!

Unique Challenges in

Hyperlipidemia

Patients intolerant to statins

Familial hyperlipidemia

Familial Hyperlipidemia (FH) Generally results in LDL >190 mg/dL

Risk of premature CHD is elevated 20-fold without treatment

Mostly caused from mutations in LDL receptor (LDLR) genes (chromosome 19) Results in loss of LDLR function, or loss of LDLRs

85%-90% of all FH

Hopkins et al. J Clin Lipidol. 2011;5(3 suppl):S9-S17.

Five Key Disorders of Familial Dyslipidemia

Disorder Prevalence

Polygenic hypercholesterolemia 1/20

Familial combined hyperlipidemia 1/100

Heterozygous familial

hypercholesterolemia

1/500

Familial defective apolipoprotein B-100 1/1000

Homozygous familial


1/1,000,000

Circulation. 2002;106(25):3143-3421

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Diagnosis of Familial

Hypercholesterolemia

Consider diagnosis for all adults (≥20 y) with LDL cholesterol ≥190 mg/dL

Collect family history of high cholesterol and heart disease in 1st-degree relatives in these patients

No gene mutation in 20% of clinically definite FH patients

Hopkins et al. J Clin Lipidol. 2011;5(3 suppl):S9-S17.

WHO Diagnostic Criteria for Familial

Hypercholesterolemia

Criteria Score

1st-degree relative with premature

CAD or LDL >95th percentile

1

1st-degree relative with tendon

xanthanoma with LDL-C >95th

percentile

2

Patient has premature CAD 2

Peripheral vascular disease 1

Tendon xanthanoma 6

Arcus cornealis <45 years 4

LDL >330 mg/dL 8

LDL 250-329 mg/dL 5

LDL 190-249 mg/dl 3

LDL 155-189 mg/dL 1

>8: Definite FH 6-8: Probable FH 3-5: Possible

WHO/HGN/FH/Cons/99.2. Geneva: WHO; 1999

Treatment Goals in FH

Patients diagnosed with FH should initiate therapy to reduce LDL ≥50%

ASAP Trial Atorvastatin 80 mg vs simvastatin 40 mg

54% LDL reduction vs 42% LDL reduction

Carotid intimal medial thickness (IMT) decreased in atorvastatin group vs increasing in simvastatin group

After switching simvastatin patients to atorvastatin, IMT arrested after 2 years of treatment

Further LDL lowering may be required to reach LDL-C goals

Robinson et al. J Clin Lipidol. 2011;5(suppl 3):S18-S29.

Patient Case

Ms. Graff is 21-year-old female presents to a local primary care

clinic for follow-up regarding family history of hyperlipidemia

LABS: WNL, except LDL: 360 mg/dL, HDL: 32 mg/dL

Medications: None

Smoking Habit: 1 pack/day

Family History:

Mother with heavily oxidized LDL >400 mg/dL, negative CAD

Father with MI at age 50

Brother without CAD, but recent LDL ~350 mg/dL

Uncle with severe hyperlipidemia and several MI’s

RX: Lovastatin 20 mg, ↑ to 80 mg

She presents 6 months later with LDL 220 mg/dL

Patient Case: Assessing the

Risk

Risk Factors: smoking, family history of CAD,

low HDL

Reynolds Score 8% risk

LDL goal: <130 mg/dL

Caveat: Many risk predictions scores are not

specific to familial hyperlipidemia. Risk of CHD

can be up to 20-fold in patients with FH.

Average LDL-C Decreases Required in FH

Baseline LDL-C

levels

190

mg/dL

220

mg/dL

250

mg/dL

280

mg/dL

310

mg/dL

To reach LDL-C <100 -32% -41% -48% -54% -58%

Civeira et al. J Clin Lipidol. 2011;5:59-517.

LDL Targets in FH

5

Non-Statin Options to reduce LDL-C

LDL-C HDL-C Triglycerides Comments

Statins

↓ 21%-55% ↑ 2%-10% ↓ 6%-30%

Fibrates ↓ 20%-25% ↑ 6%-18% ↓ 20%-35% Gemfibrozil

may increase

LDL 10%-15%

Bile Acid

Sequestrants

↓ 15%-25% No effect May increase Colesevelam ↓

HbA1c ~0.5%

Cholesterol

Absorption

Inhibitors

↓ 10%-25% No effect ↓ 2%

Niacin ↓ 10%-25% ↑ 10%-35% ↓ 20%-30%

Jellinger et al. Endocr Pract. 2012;18(suppl 1):1-78.

Ezetimibe (Zetia®)

Ezetimibe Metabolic Effects

Reduces LDL-C by 10%-25%

Results in additional LDL-C reductions of

23%-30% when added to statin therapy

Reduces LDL-C by an additional 20%-22%

when combined with fibrates

No morbidity/mortality data as monotherapy

Very well tolerated

Bays et al. Clin Ther. 2001;23:1209-1230.

Dujovne et al. Am J Cardiol. 2002;90:1084-1091.

Ezetimibe Combination Therapy

ENHANCE TRIAL

Pts with FH with an LDL

≥210 mg/dL

Simvastatin 80 mg plus

placebo or ezetimibe10 mg

Followed for 24 months

Primary Outcome;

Change in carotid artery

intimal medial thickness

Results: No difference with

addition of ezetimibe

N Engl J Med. 2008;358:1431-1443.

Limitations to ENHANCE

80% of participants had received long-term statin therapy prior to the trial

Did not address actual clinical outcomes

Ongoing trial, IMPROVE-IT, plans to be completed in 2013 to address clinical outcomes of ezetimibe added to simvastatin therapy

Toth et al. J Clin Lipidol. 2010;5:655-684.

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SEAS Trial

Patients with aortic stenosis Simvastatin 40 mg plus

ezetimibe 10 mg or placebo

Excluded patients with CAD or DM

Mean LDL at baseline 140 mg/dL

LDL reduction ~50% in simvastatin/ezetimibe group

Rossebo et al. N Engl J Med. 2008;359:1343-1356.

0%5%

10%15%20%25%30%35%40%45%

CV Eve

nts

Ischem

ic Eve

nts

Cancer

Placebo

Simvastatin/Ezetimibe

SHARP TRIAL

Lancet. 2011;377:2181-2192.

Patients with chronic kidney disease

Simvastatin 20 mg plus ezetimibe 10 mg or placebo

Excluded patients with CAD or DM

Mean LDL at baseline 108 mg/dL

LDL reduction ~30% in simvastatin/ezetimibe group

No difference in cancer

Fibric Acid Derivatives

“Fibrates”

Fibrate Metabolic Effects

Fenofibrate, fenofibric Acid, and gemfibrozil

↑ HDL 6%-18%, ↓ TG 20%-35%,

↓ LDL 20%-25%

Gemfibrozil

May not change or even increase LDL in severe hypertriglyceridemia

Not indicated for FH, unless severely hypertriglyceridemic (FCH)

Cardiovascular benefit as monotherapy (VA-HIT, BIP, Helsinki Heart trials)


Fibrate Combination Therapy

ACCORD Study

5518 patients with type 2 diabetes on simvastatin

Given fenofibrate or placebo

Mean LDL ~100 mg/dL

No difference in CV events

Subgroup analysis of patients with triglycerides

>204 mg/dL and HDL ≤ 34 mg/dL showed

reduction in CV events

N Engl J Med. 2010; 362:1563-1574.

Fibrate Adverse Effects and

Drug Interactions

Adverse Effects

Dyspepsia, upper GI complaints, gallstones, and

myopathy

Contraindicated in severe renal disease

Drug Interactions

Gemfibrozil ↑ concentration

Statins

Repaglinide, thiazolidinediones, and sulfonylureas

Warfarin (displaces protein-bound warfarin)

Fenofibrate safer with statins

7

Niacin

Niacin Metabolic Effects

Mortality benefit with monotherapy

↓ LDL 10%-25%, ↓ TG 20%-30%, ↑ HDL 10%-35%

Increases Blood Glucose Usually returns to baseline at 14-32 weeks

NOT a contraindication in diabetes

Flushing (up to 88% may experience) Diminishes with continued use

Discontinuation in clinical trials (~6%)

Less with extended-release niacin

Can pretreat with aspirin 325 mg


Elam et al. JAMA. 2000;284:1263-1270. Grundy et al. Arch Intern Med. 2002;162:1568-1576.

Vittone et al. J Clin Lipidol. 2007;1:203-210. Canner et al. J Am Coll Cardiol. 1986;8:1245-1255.

Niacin Combination Therapy

HATS Study Simvastatin plus niacin in patients with CAD

Decreased LDL by 42% decreased CV events

Mean LDL 113 mg/dL

FATS Study Niacin + colestipol

Decreased LDL 32%, and decreased rates of CV events

HATS/FATS were small trials

HPS-2 THRIVE Ongoing Expected results 2013

Brown et al. N Engl J Med. 2001;345:1583–159.2 Am Heart J. 2011;161:538-543.

Niacin Combination Therapy

AIM-HIGH Trial

Niacin 1500-2000 mg/day or placebo in

addition to simvastatin 40-80 mg in patients

with CHD

LDL reduced from 74 mg/dL 62 mg/dL

No difference in CV events between groups HPS-2 THRIVE

Ongoing Expected results 2013

NEJM 2011; 365:2255-2267

Bile Acid Sequestrants

(BAS)

BAS Metabolic Effects

Demonstrated reduction in coronary events as monotherapy

Cholestyramine/colestipol/colesevelam

↓ LDL-C by 15%-25%, ↑ HDL by 4%-8%.

May increase triglycerides

Poorly tolerated GI side effects (~40% discontinuation rate) Colesevelam may be better tolerated


Andrade et al. N Engl J Med. 1995;332:1125-1131. Prosbstfield and Rifkind. Eur J Clin Pharmacol. 1991;40:S69-S75.

8

Bile Acid Sequestrants

GLOWS Study

Colesevelam ↓ glucose (↓ HbA1c 0.5%)

January 2008FDA approval as an adjunct glucose-

lowering therapy for type 2 diabetes

FATS Study

Lovastatin + colestipol ↓ LDL 46%

Niacin + colestipol ↓ LDL 32%

Both groups had less arthrosclerosis progression

Both groups had lower rates of death, MI, or

revascularization

SMALL Study

Zieve et al. Clin Ther. 2007;29:74-83. Zhao et al. Am J Cardiol. 2009;104:1457-1464.

BAS Dosing and Adverse

Effects

Dosing Colesevelam: 1.875 g (3 tabs) BID or 3.75 g daily

Cholestyramine: 4 g 1-2x/day, increase monthly up to 16-24 g, as tolerated.

Colestipol: 2 g 1-2x/day, increase monthly by 2-4 g per day as tolerated to maximum 16 g

Adverse Effects Constipation, abdominal pain, bloating, nausea,

flatulence

Administer with food

BAS Drug Interactions

Drug Interactions: ↓absorption of many meds

Cholestyramine: Take other medications at least

1 hour prior and 4-6 hours after cholestyramine

Colesevelam:

Cyclosporine, glimepiride, glipizide, glyburide,

levothyroxine, olmesartan, OC’s should be taken at

least 4 hours prior to colesevelam

These are only known drug interactions; use caution

with all meds

Question

Ms. Graff presents on 80mg of Simvastatin

and an LDL of 220 mg/dl (goal 130mg/dl).

What should be the next step?

A. Access Diet

B. Change to higher potency statin

C. Add additional therapy.

D. All of the above

Patient Case

LDL 220 mg/dL on 80 mg lovastatin

Patient changed diet to vegetarian and quit

smoking

Atorvastatin 80 mg added along with

cholestyramine (titrated to 12 g BID)

LDL after 12 months116 mg/dL

Patient Case

Ms. Graff doing well; however, after 2 years

patient stops taking cholestyramine

secondary to poor palatability

LDL-C now 150 mg/dL (HDL 30 mg/dL)

What is our next step?

9

Question

What alternative for cholestyramine would be

best for Ms. Graff?

A. Colesevelam

B. Ezetimibe

C. Niacin

D. Gemfibrozil

Statin-Associated

Adverse Effects

Myopathy

Definitions

Myalgia: symptoms without creatine kinase (CK) elevations

Myositis: symptoms with CK elevations

Rhabdomyolysis: symptoms w/ CK elevations >10x normal

Rare: ~1/3400 pts will experience creatinine kinase elevations >10x or rhabdomyolysis

“Real-world” experience with higher incidence

PRIMO database muscle symptoms ~10% of patients

Can occur at any dose

More common with lipophilic statins (simvastatin/lovastatin)

Silva et al. Clin Ther. 2006;28:26-35.

Bruckert et al. Cardiovasc Drugs Ther. 2005;19:403-414.

Mechanisms of Myopathy

No one really knows

Coenzyme Q-10 deficiency

↓ mitochondrial respiratory function

Induced myocyte death through decrease

in isoprenoid production

Genetic variants on chromosome 12 that

affect statin blood levels

Arca et al. Diabetes Metab Syndr Obes. 2011;4:155-16.6

Liver Toxicity

AST/ALT elevations Transaminitis

Dose-related

Usually resolves within 4 weeks after discontinuation

More common with less lipophilic statins (pravastatin, rosuvastatin, atorvastatin, fluvastatin)

February 2012: FDA recommended removal of routine liver function test monitoring for all statins

Arca et al. Diabetes Metab Syndr Obes 2011; 4: 155-166

Dale et al. Am J Med. 2007; 120: 706-712

Management of Statin

Intolorance

Myositis and Transaminitis

10

Assess Possible Confounders

Statin-Induced Myopathy Hepatic Toxicity

High physical activity Acute viral disease

(hepatitis)

Heavy alcohol consumption Alcoholic liver disease

Drugs affecting statin

concentrations

- gemfibrozil, cyclosporine,

amiodarone, macrolides,

verapamil, fluconazole, HIV

medications

Grapefruit juice

Hypothyroidism

Major surgery

Arca et al. Diabetes Metab Syndr Obes. 2011;4:155-166.

Switching Statins

Hansen et al.

37 patients with statin-induced myositis changed statin

43% tolerated a new statin

Glueck et al.

61 patients with statin intolerance secondary to myalgias

Given rosuvastatin 5 mg or 10 mg per day

All patients except one tolerated therapy,

with LDL reductions ~40%.

Hansen et al. Arch Intern Med. 2005;165:2671-2676.

Glueck et al. Clin Ther. 2006;28:933-942.

Alternate-Day Statin Dosing

Trialed with several statin therapies

Most efficacious for statins with long half-life

Atorvastatin

T1/2:14 hr2 metabolites (T1/2 20-30 hr)

Metabolites contribute to 70% of activity

Rosuvastatin

T1/2: 19 hr


Alternate-Day Dosing Trials

Regimen LDL-C Effect

Atorvastatin 10 mg QOD ↓ 30% after 8 weeks

Atorvastatin 20 mg/day

Atorvastatin 20 mg QOD

↓ 41 % after 3 months

↓ 36% at 1 month, ↓ 46% at 3 months

Atorvastatin 10 mg/day, then

10 mg QOD for 12 weeks

↓ 39% on daily regimen

↓ 23% after switching to QOD dosing

Rosuvastatin 5 mg M-W-F

Rosuvastatin 2.5 mg M-W-F

↓ 38% after 6 weeks

↓ 20% after 6 weeks

Rosuvastatin 2.5 mg to 20 mg once

weekly

↓ 23% after 4 months

Ezetimibe 10 mg/day, then add

atorvastatin 10 mg twice weekly

9% of patients achieved LDL goal on

ezetimibe alone vs 84% with the

combination

Piamsomboon et al. J Med Assoc Thai. 2002;85:297-300.

Keles et al. Anadolu Kardiyol Derg .2008;8:407-412.

Ferrer-Garcia et al. Acta Diabetol. 2006;43:75-78.

Mackie et al. Am J Cardiol. 2007;99:291.

Ruisinger et al. Am J Cardiol. 2009;103:393-394.

Management of Myalgias

Tolerable muscle pains and CK <5x ULN

Continue or reduce dosage

CK >5x ULN or intolerable

muscle pains

Discontinue statin. Restart when symptoms disappear at

lower dosage or different statin

If symptoms recur with multiple statins at low doses, start non-statin

lipid-lowering agents.

If symptoms recur, consider: - Rosuvastatin 2.5-5 mg daily

- Rosuvastatin 5-10 mg - Atorvastatin 10-20 mg every other day

Rhabdomyolysis

Consider risk-benefit of statin therapy


Management of Transaminitis

AST/ALT <3x ULN

Continue statin, recheck in 6 months

Consider other causes (alcohol)

AST/ALT >3x ULN

Hold statin therapy

Consider other causes (viral, alcohol, other drugs)

Rechallenge when enzymes decrease.

Consider lower-dose statin or changing to another statin (simvastatin/lovastatin)


11

Dietary Manipulation

Jenkins study showed specific dietary portfolio was equivalent to lovastatin 20 mg

<7% calories from saturated fat, < 200 mg cholesterol

Provided the following per 1000 kcal 1 g of plant sterol (enriched margerine)

9.8 g of viscous fibers (eggplant and okra)

21.4 g of soy protein (soy milk)

14 g of almonds

Both groups ↓ LDL ~30%

Jenkins et al. JAMA. 2003;290:502-510.

Dietary Recommendations:

2500 Kcal Diet

<7% of calories from saturated fat175 kcal (17g)

Transfat <1%25 kcal (1 g)

Cholesterol <200 mg/day

Total fat ~25%-35% of calories(75 g)

Soluble fiber 10-25 g per day Oat bran, oatmeal, beans, peas, rice bran, barley, citrus fruits,

strawberries

Plant stanols 2 g/day (inhibit cholesterol absorption) Nuts, legumes

Margarine spreads Smart Balance with Heart Right®, Promise Activ® light spread

Nutraceuticals

Red yeast rice

Natural monacolin Inhibits HMG-CoA reductase

LDL 13%-25%

1800-2400 mg BID

Others

Phytostanols, berberine

Questionable cardiovascular benefit

4th-line approaches


Coenzyme Q-10

100 mg/day shown in one study to decrease pain severity by 40%

Studied in small populations (<20 patients)

Mostly anecdotal reports

Not supported by current guidelines

Caso et al. Am J Cardiol. 2007;99:1409-1412.

Other Statin Concerns

Memory loss/dementia

Some evidence statins improve dementia

Case reports of acute memory loss or feeling

“cloudy,” with reversibility upon stopping

Diabetes

Patients with risk factors for diabetes may be at

increased risk

Cardiovascular benefit likely outweighs any risk of

developing diabetes

http://www.fda.gov/Drugs/DrugSafety/ucm293101.htm

Ridker et al. Lancet. 2012;380:565-571.

ATP IV: Coming in 2013?

Fixed-dose statin? Forget about LDL?

Combination therapy

To achieve LDL <70 mg/dL?

Raising HDL

HPS-2 and IMPROVE-IT trials (awaiting results)

High-sensitivity C-reactive protein (hsCRP)

Other targets of lipid therapy

Apolipoprotein B level

12

Newly Approved Therapy:

Juxtapid® (Lomitapide)

FDA approval in December 2012 for

homozygous familial hypercholesterolemia

Microsomal triglyceride transport protein

inhibitor ↓ secretion of Apo-B lipoproteins

Studied in 29 patients on statin therapy, and

in most cases ezetimibe

LDL 339167 mg/dL

Available through REMS only (1-85Juxtapid)

Cuchel et al. Lancet. 2013;381:40-46.

Newly Approved Therapy:

Kynamro® (Mipomersen)

FDA approved for homozygous familial


Inhibits Apo-B production

200 mg SQ weekly

Decreases LDL ~25%

Available through special distribution

Patients must be monitored for hepatotoxicity

Thank You!

Documents

Complicated Dyslipidemia: Beyond First Line Therapy · Managing the Complicated Dyslipidemia Patient: Beyond First-Line Therapy Patrick Curtin, ... Civeira et al. J Clin Lipidol