Transcript Slide 1

Health benefits and safety
profile of omega-3 fatty acids in
heart failure and CHD
Jodi N. Sparkman PharmD, BCPS, NCPS
LCDR USPHS
Clinical Pharmacist
Claremore Indian Hospital, Inpatient Pharmacy Director
May 26, 2010
1
Objectives
 Identify doses at which omega-3 fatty
acids provide cardiovascular benefit
 Describe the health benefits on omega-3
fatty acids
 Describe the adverse effects related to
treatment with omega-3 fatty acids
2
What are Omega-3 Polyunsaturated
Fatty Acids (PUFAs) and How Do They
differ from other Essential Fatty Acids?
 Essential fatty acids cannot be made in the body
because the desaurase enzymes required for
adding double bonds on the CH3 end of these
molecules are not present in mammals
 For the most part, EPA and DHA must be
ingested from external sources: arachidonic acid
is easily made from linoleic acid
3
Essential Fatty Acid Families
ω-3 family
ω-6 family
H3C
C18:2 ω-6
COOH
Linoleic
• Corn Oil
• Safflower Oil
• Sunflower Oil
H3C
H3C
C18:3 ω-3
H3C
COOH
C20:4 ω-6 Arachidonic
COOH
-Linolenic
• Flaxseed Oil
• Canola Oil
• Soybean Oil
COOH
C20:5 ω-3 Eicosapentaenoic
(EPA)
H3C
COOH
C22:6 ω-3 Docosahexaenoic
(DHA)
More thrombotic
and inflammatory
metabolites
Less thrombotic
• Oily Fish
and inflammatory • Fish Oil Capsules
metabolites
4
Sources of EPA and DHA
Fish
Amount (g) in Serving amount
3 oz serving required to provide
1 g of EPA/DHA
Mackerel
0.34-1.57
2-8.5
Herring
1.71-1.81
1.5-2.0
Salmon
0.68-1.83
1.5-4.5
Trout
0.84-0.98
3.0-3.5
Catfish
0.1-2.0
15-20
Flounder/Sole 0.42
7
Cod
0.1-0.24
12.5-23
Tuna, fresh
0.24-1.28
Kris-Etherton, et al. Circulation. 2002;106:2747-2757.
2.5-12
5
Sources of EPA and DHA
Supplements Amount (g) in
1 gram
capsule
Cod Liver Oil
0.19
Fish Body Oil
0.30
Omega-3
concentrate
0.5
Rx omega-3
FA
concentrate
0.85
Kris-Etherton, et al. Circulation. 2002;106:2747-2757.
Capsules required
to provide 1 g of
EPA/DHA
5.0
3.0
2.0
1
6
The Potential Cardiovascular
Benefits of EPA and DHA
 Antilipid
 Antiarrhythmia
 Antiatherogenic
 Antithrombotic
 Anti-inflammatory
 Antihypertensive
7
GISSI-HF omega-3 fatty acid study:
Primary and secondary outcomes
End point
Omega-3 fatty
acids, n=3494(%)
Placebo
n=3481 (%)
Adjusted hazard
ratio (95% CI)
Mortality
27.3
29.1
0.91 (0.833–0.998)
All-cause mortality or
hospitalization for
cardiovascular causes
56.7
59.0
0.92 (0.849–0.999)
Death from cardiovascular
causes
20.4
22.0
0.90 (0.81–0.99)
Sudden cardiac death
8.8
9.3
0.93 (0.79–1.08)
Patients admitted for
cardiovascular causes
46.8
48.5
0.93 (0.87–0.99)
Patients with fatal and
nonfatal MI
3.1
3.7
0.82 (0.63–1.06)
Patients with fatal and
nonfatal stroke
3.5
3.0
1.16 (0.91–1.53)
Primary end points
Secondary end points
GISSI-HF investigators. Lancet 2008; available at: http://www.thelancet.com.
8
GISSI-HF : More outcomes
 Number needed to treat
– All cause mortality = 56
– All cause mortality or hospitalization for
cardiovascular cause = 44
 When 1,000 patients were treated with
omega-3 FA for ~4 years, 18 lives were
saved and 17 cardiovascular
hospitalizations were prevented
GISSI-HF investigators. Lancet 2008; available at: http://www.thelancet.com.
9
10
GISSI-Prevenzione Trial:
Endpoint Results
Endpoint
All-cause
mortality
CV death
Cardiac
Death
Sudden
Death
Non-fatal
CV events
Control Omega- Risk
P-value
(%)
3 FA (%) Reduction(%)
10.4
8.3
20
0.0064
6.8
4.8
30
<0.001
5.3
3.5
35
<0.01
3.5
1.9
45
0.0006
5.1
4.9
4
NS
GISSI Prevenzione Investigators. Lancet. 1999;354:447-455.
11
Relative Risk of a Clinical Endpoint with
Supplemental Omega-3 FA: Meta Analysis
 9 studies, randomized, controlled, N= 13,168
 Dose range= EPA 0.3 to 6.0 g/day and DHA 0.6
to 3.7 g/day
 Included pts with and without CHD
 Mean Duration 20 months
Nonfatal MI
Sudden Death Overall
Mortality
0.8 (0.55 to 1.2) 0.7 (0.6 to 0.9)
Bucher et al. Am J Med. 2002;112:298-304.
0.8 (0.7 to 0.9)
12
Possible Benefits
 Treatment with n-3 fatty acids may be
associated with reductions in plasma levels
of tumor necrosis factor-α and interleukin1β in healthy subjects
 Disadvantages with studies
Large doses
Small sample size
G.E. Caughey, E. Mantzioris, R.A. Gibson, L.G. Cleland and M.J. James, The effect on human tumor necrosis factor α
and interleukin1 β production of diets enriched in n-3 fatty acids from vegetable oil or fish oil, Am J Clin Nutr . 1996;
63:116–122.
S. Endres, R. Ghorbani, V.E. Kelley, K. Georgilis, G. Lonnemann, J.W. van der Meer, J.G. Cannon, T.S. Rogers, M.S.
Klempner, P.C. Weber, E.J. Schaefer, S.M. Wolff and C.A. Dinarello, The effect of dietary supplementation with n-3
polyunsaturated fatty acids on the synthesis of interleukin-1 and tumor necrosis factor by mononuclear cells, N Engl J
Med. 1989; 320:265–271.
13
Possible Benefits
 Weight Loss
Obese people had blood levels of omega-3 fatty acids
almost 1% less than those at a healthy weight
 Higher plasma levels of total n-3 PUFA are
associated with a healthier BMI, waist
circumference and hip circumference.
M Micallef, I Munro, M Phang, M Garg. Plasma n-3 poluunsaturate fatty acids are negatively associated with obesity.
Br Jof Nutr .2009; 102:1370-1374.
14
15
16
17
18
Risk for Primary Cardiac Arrest and
Red Blood Cell EPA+DHA Level
1.0
90%
reduction
in risk
Odds Ratio
0.8
0.6
*p<0.05
vs Q1
0.4
0.2
0.0
3.3%
4.3%
5.0%
6.5%
Mean RBC EPA+DHA by Quartile
Adapted from Siscovick DS et al. JAMA 1995;274:1363-1367.
19
Summary of AHA
Recommendations for Omega-3 FA
 Patients without CHD
Eat a variety of fish at least
twice a week
 Patients with CHD
1 Gram of EPA/DHA per day,
preferably from fatty fish;
supplements only under
physician’s care
 Patients who need to
lower triglycerides
2 to 4 grams of EPA/DHA per
day under a physician’s
care
20
Kris-Etherton PM, et al. Circulation. 2002;106:2747-2757.
Summary of NCEP ATP III
Recommendations for Omega-3 FA
 Patients with elevated
triglycerides
 Patients with CHD
An alternative to fibrates
or niacin at doses of 3 to
12 g/day
A therapeutic option in
secondary prevention in
doses 1 to 2 g/day
(moderate evidence)
Expert Panel on Detection, Evaluation, and Treatment of High Blood
Cholesterol in Adults. Circulation. 2004;110: 227-230.
21
Research in Progress
 VITAL Study
– Vitamin D and Omega-3 trial
– 20,000 patients
– Women >65 and men >60
– Follow-up 5 years
– At least 25% African American
– primary end point is a composite of nonfatal
MI, nonfatal stroke, or vascular death
22
Implications for Research
 Further trials with prespecified cardiovascular
endpoints including sudden cardiac death, and
blinding of participants and health providers are
needed to test for any protective effect of omega
3 fats for those at increased cardiovascular risk,
to run for long enough to assess long term
events (ideally beyond four years), and to report
any adverse effects associated with treatment
(including cancer diagnosis, different types of
stroke, and neurological status).
23
Implications for Research
 At present almost no RCT data exist on
health outcomes in healthy populations,
hopefully the VITAL study will provide
answers in this population.
 The association between exposure to fat
soluble toxins from fish and risk of MI or
CHD should also be examined.
24
Implications for Research
 Trials assessing higher doses of omega-3
fatty acids. Many studies use around 1
gram/day. Trials with >3 grams daily are
warranted.
25