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Health benefits and safety profile of omega-3 fatty acids in heart failure and CHD

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. Objectives.

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Health benefits and safety profile of omega-3 fatty acids in heart failure and CHD

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  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

  2. 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

  3. 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

  4. H3C H3C COOH COOH Essential Fatty Acid Families ω-3 family ω-6 family C18:3 ω-3 • -Linolenic • Flaxseed Oil • Canola Oil • Soybean Oil C18:2 ω-6 Linoleic • Corn Oil • Safflower Oil • Sunflower Oil H3C COOH H3C C20:5 ω-3 Eicosapentaenoic (EPA) COOH C20:4 ω-6 Arachidonic H3C COOH C22:6 ω-3 Docosahexaenoic (DHA) Less thrombotic and inflammatory metabolites More thrombotic and inflammatory metabolites • Oily Fish • Fish Oil Capsules

  5. Sources of EPA and DHA Kris-Etherton, et al. Circulation. 2002;106:2747-2757.

  6. Sources of EPA and DHA Kris-Etherton, et al. Circulation. 2002;106:2747-2757.

  7. The Potential Cardiovascular Benefits of EPA and DHA • Antilipid • Antiarrhythmia • Antiatherogenic • Antithrombotic • Anti-inflammatory • Antihypertensive

  8. GISSI-HF omega-3 fatty acid study: Primary and secondary outcomes GISSI-HF investigators. Lancet 2008; available at: http://www.thelancet.com.

  9. 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.

  10. GISSI-Prevenzione Trial:Endpoint Results GISSI Prevenzione Investigators. Lancet. 1999;354:447-455.

  11. 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 Relative Risk of a Clinical Endpoint with Supplemental Omega-3 FA: Meta Analysis Bucher et al. Am J Med. 2002;112:298-304.

  12. Possible Benefits • Treatment with n-3 fatty acids may be associated with reductions in plasma levels of tumor necrosis factor-α and interleukin-1β 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. Risk for Primary Cardiac Arrest and Red Blood Cell EPA+DHA Level 90%reductionin risk *p<0.05 vs Q1 Odds Ratio 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.

  15. Patients without CHD Patients with CHD Patients who need to lower triglycerides Summary of AHA Recommendations for Omega-3 FA Eat a variety of fish at least twice a week 1 Gram of EPA/DHA per day, preferably from fatty fish; supplements only under physician’s care 2 to 4 grams of EPA/DHA per day under a physician’s care Kris-Etherton PM, et al. Circulation. 2002;106:2747-2757.

  16. Patients with elevated triglycerides Patients with CHD Summary of NCEP ATP III Recommendations for Omega-3 FA 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.

  17. 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

  18. 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).

  19. 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.

  20. 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.

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