Treatment of

hypertriglyceridemia:

Lovaza vs. Nicotinic acid

Melissa Johnson, PA-S

Shenandoah University PA Studies

December 10, 2008

Introduction1,2

Hypertriglyceridemia has a large impact on

healthcare today.

Hypertriglyceridemia is a major cause of

atherosclerosis which is a risk factor for

CAD, CVA, PVD, acute pancreatitis and is a

factor in metabolic syndrome.

Hypertriglyceridemia is exacerbated by

uncontrolled DM, obesity, tobacco

smoking, high fat diets and sedentary

lifestyle.

Impact on healthcare3-7

Hypertriglyceridemia accounts for 1-4% of hospitalized acute pancreatitis cases per year.

Prevalence of metabolic syndrome is 22% in US.

Heart disease is the 1st leading cause of death and CVA’s are the 3rd in US today accounting for more than 35% of deaths in the US.

The economic impact on US healthcare is estimated to be $448 billion dollars for the year 2008.

Background1,4,8,9

Two classification systems for

hypertriglyceridemia: Fredrickson and clinical.

Fredrickson is not used as much, but will still

be found in literature today.

Both classifications help to clarify the many

terms used today to describe derangements

in the lipid panel.

Background

Hyperlipoproteinemia according to Fredrickson classificationa

Fredrickson

classification

Clinical

classification

terminology

Subset of clinical

classificationEtiology Laboratory findings

Type I

Triglyceride

dominant lipid

disorder

Familial

hyperchylomicronemiaDecreased LPL

Elevated chylomicrons

and

triglycerides

Type IIaLDL-dominant

lipid disorderFamilial hypercholesterolemia LDL receptor deficiency Elevated LDL only

Type IIbMixed lipid

disorder

Familial combined

hyperlipidemia

Decreased LDL receptor and

increased ApoB protein

Elevated LDL, VLDL, and

triglycerides

Type IIILDL-dominant

lipid disorder

Familial

dysbetalipoproteinemia

Defect in ApoE protein

synthesisIncreased IDL and LDL

Type IV

Triglyceride

dominant lipid

disorder

Endogenous hyperlipemia and

atherogenic dyslipidemia

Increased VLDL production

and decreased elimination

Increased VLDL and

Triglycerides and low

HDL

Type V

Triglyceride

dominant

disorder

Familial and severe

hypertriglyceridemia

Increased VLDL

production and decreased

LPL

Increased VLDL,

chylomicrons, and

triglycerides

aYuan, Al-Shali, Hegele and Eaton

Background6-14

Diagnosis:

Triglycerides:

<150: normal

150-199: borderline high

200-499: high

>/= 500: SEVERE

Clinical presentation:

Most often asymptomatic

Can present with acute

pancreatitis, eruptive

cutaneous xanthomas,

lipemia retinalis

Current First Line Therapy4-8,16

Current first line therapy recommended by

the NCEP-ATPIII guidelines are the use of

fibrates and nicotinic acid for the treatment of

elevated triglycerides.

Clinicians must also ensure that goal LDL has

been reached first in patients with elevated

triglycerides.

Purpose

To evaluate the treatment of severe

hypertriglyceridemia (triglycerides >/= 500mg/dl)

with Lovaza vs. Nicotinic Acid.

To evaluate which medication as a

monotherapy is more effective and with less

side effects for all patients including those

with comorbidities.

Literature Review/Methods

Databases available through Shenandoah University Library searched included: Cochran, PUBMED, and Medline.

Inclusion Criteria: Clinical overviews, RCT, open label trials, systemic

reviews and prospective studies.

Studies must have utilized Lovaza or Nicotinic Acid and include measurements of triglycerides.

Exclusion Criteria: Lipid derangements not including elevated

triglycerides.

Studies before 1997.

Studies using Lovaza or Nicotinic acid to treat elevated triglycerides induced by medications.

Study 1 Harris WS, et al. (1997). Safety and efficacy of omacor in

severe hypertriglyceridemia. Journal of Cardiovascular

Risk.1997;4(5/6), 385-391.

■ Objective: Evaluate the efficacy and safety of Omacor (now known as Lovaza) in patients with severe hypertriglyceridemia.

Methods: Randomized, double-blind, prospective, parallel-group study comparing Omacor to placebo in 42 patients with triglycerides between 500-2000mg/dl. Patients received 4g of Omacor once daily or placebo for four months.

Results: mean baseline triglycerides: 919mg/dl +/-381. Mean end triglycerides: 505mg/dl +/- 304.

Side effects: 7 patients reported GI problem: 3 of which were in placebo group. Most common was burping a fishy taste.

Study 2 Capuzzi DM, et al. Efficacy and safety of an extended-

release Niacin (Niaspan): a long term study. The American Journal

of Cardiology. 1998; 82(12A), 74U-81U

Objective: Evaluate long term safety and efficacy of Niaspan once nightly in patients with primary hypercholesterolemia. Secondary goal to evaluate effects on triglycerides.

Methods: Open-label extension trial evaluating Niacin doses of 1000-3000mg nightly. 723 patients at 27 sites were followed for 24 months.

Results: Triglycerides were lowered by 28% after 96 weeks of therapy.

Side effects: flushing, HA, abdominal pain, diarrhea, dyspepsia, N/V, rhinitis, pruritus and rash.

75 patients did experience serious & unexpected AE’s warranting hospitalization. 3 considered directly related to Niaspan, 64 were

considered not related and 8 were considered remotely related to Niaspan.

Results

Summary of results

Study 1a Study 2b

Sample size 42 723

Date of publication 1997 1998

Study design RCT-prospective Open label extension

Intervention 4g Omacor daily 1-3g Niaspan daily

Outcome Triglyceride level

1 LDL, apo B

2 triglycerides, total cholesterol,

HDL, lipoprotein (a)

Results Triglycerides down by 45% Triglycerides down by 28%

Conclusion Omacor reduces triglycerides Niaspan reduces triglycerides

Level of evidence 1b 1c

aHarris, Ginsberg, Arunakul, Shachter, Windsor, Adams, Berglund, OsmundsenbCapuzzi, Gyton, Morgan, Goldberg, Kreisberg, Brusco, Brody

Discussion

Study #1: Level of evidence 1b

Prospective randomized controlled study

Patients treated with Lovaza 4g or placebo

Study #2: Level of evidence 1c

Open label extension trial

All patients treated with Niaspan 1-3g

No placebo group

Strengths and limitations

Strengths:

Beneficial for primary care providers looking for an

appropriate, safe, and effective treatment for patients

with severe hypertriglyceridemia.

Limitations:

Limited to patients with triglyceride levels between 500-

2000mg/dl or at elevated triglycerides as a secondary

goal.

Limited by English language, available databases and

head to head study between Lovaza and Niaspan.

Conclusion

Lovaza yields higher results at lowering

triglycerides than Niaspan.

Lovaza has fewer side effects and adverse

events than Niaspan.

Lovaza is better tolerated than Niaspan.

Acknowledgements

Raymond Eifel, MS, PA-C

Advisor for scholarly project

Associate Professor Shenandoah University

Physician Assistant Studies

References

1. Pejic R, Lee DT. Hypertriglyceridemia. Journal of the American board of family medicine. 2006:19(3):310-316.

2. Citkowitz E. Hypertriglyceridemia. Emedince: The medscape Journal [serial online]. July 12, 2008. www.emedicine.com/med/TOPIC2921.HTM. Accessed June 23, 2008.

3. Ferrannini E. Metabolic syndrome: a solution in search of a problem. Journal of Endocrinology Metabolism. 2007;92:39-401.

4. Yuan G, Al-Shali K, Hegele R. Hypertriglyceridemia: its etiology, effects and treatment. Canadian Medical Association Journal. 2007;176:1113-1120.

5. National Health and Nutrition Examination Survey [webpage]. Center for disease control website. http://www.cdc.gov/nchs/nhanes.htm. Accessed July 10, 2008.

6. Grundy M, Becker D, Clark L, Cooper R, et al. National Cholesterol Education Program Expert Panel on detection, evaluation and treatment of high blood cholesterol in adults (adult treatment panel III). NIH publication No. 02-5215. September 2002.

7. Grundy SM, Cleeman JI, Merz NB, et al. Third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation and treatment of high blood cholesterol in adults (Adult Treatment Panel III). Implications of recent clinical trials for the national cholesterol education program adult treatment panel III guidelines. 2004. National Heart, Lung and Blood Institute: NIH. http://www.nhlbi.nih.gov/guidelines/cholesterol/atp3upd04.htm. Assessed March 23, 2008

8. Eaton C. Hyperlipidemia. Primary care: clinics in office practice. 2005;32(4):1027-1055.

References Cont’

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17. Harris WS, et al. Safety and efficacy of Omacor in severe hypertriglyceridemia. Journal of Cardiovascular Risk. 1997;4(5/6):385-391.

18. Capuzzi DM, et al. Efficacy and safety of extended-release Niacin (Niaspan): a long term study. The American Journal of Cardiology. 1998;82(12A):74U-81U.