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The Big Ones That Got Away: Omega-3 Meta-analysis Flawed by Excluding the Biggest Fish Oil Trials—Reply

The Big Ones That Got Away: Omega-3 Meta-analysis Flawed by Excluding the Biggest Fish Oil... In reply We appreciate the letter of DiNicolantonio et al in response to our report1 in the Archives. We acknowledge that several methodologic issues raised by DiNicolantonio et al are important for our main conclusions. First, regarding the small sample size and short follow-up period, we stated in the limitations of the “Comment” section1(p693) that Fifth, most trials included in the present meta-analysis had a small sample size of 59 to 500 participants and a short duration of treatment of less than 2 to 3 years. Further larger trials are needed. However, although we included trials with a small sample size of participants, the number of total participants in the meta-analysis was more than 20 000, which is regarded as having enough power to detect a difference in cardiovascular outcomes. Second, regarding the exclusion of the 5 trials with the use of olive oil as a control group, when we performed a subgroup meta-analysis with excluding those 5 trials, no preventive effect of omega-3 fatty acid supplementation on overall cardiovascular events was observed (relative risk [RR], 0.94; 95% CI, 0.83-1.07). Also, when we performed a meta-analysis without the trial by Kromhout et al2 that used margarine spread, there was no preventive effect (RR, 0.98; 95% CI, 0.86-1.11). Third, the Diet and Reinfarction Trial (DART)3 that DiNicolantonio et al mentioned is not a relevant trial for our meta-analysis because it used only advice on an increase in fatty fish intake, not omega-3 fatty acid supplementation. Last, regarding the exclusion of the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (GISSI)-Prevenzione4 and Japan Eicosapentaenoic Acid Lipid Intervention Study (JELIS)5 in our analysis, we already addressed in the “Comment” section. Again, the main reason that we excluded those 2 large randomized controlled trials is that they used an open-label design without using placebos, which is liable to performance bias. For the readers who have the same question, in our article1(p691) we already mentioned that When we performed a meta-analysis with the GISSI-Prevenzione trial[4] and the JELIS[5] in addition to the 14 trials included in the present study, a preventive effect of omega-3 fatty acid supplementation was not observed (RR, 0.95; 95% CI, 0.87-1.03; I2=35.5%) (data not shown). In conclusion, despite some methodologic issues and limitations, our meta-analysis indicates that there is a lack of sufficient evidence of the secondary preventive effects of omega-3 supplementation on cardiovascular disease. Further larger randomized, double-blind, placebo-controlled trials are needed to confirm our findings. Back to top Article Information Correspondence: Dr Myung, Carcinogenesis Branch, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi 410-769, Republic of Korea (msk@ncc.re.kr). Financial Disclosure: None reported. References 1. Kwak SM, Myung SK, Lee YJ, Seo HG.Korean Meta-analysis Study Group. Efficacy of omega-3 fatty acid supplements (eicosapentaenoic acid and docosahexaenoic acid) in the secondary prevention of cardiovascular disease: a meta-analysis of randomized, double-blind, placebo-controlled trials. Arch Intern Med. 2012;172(9):686-69422493407PubMedGoogle Scholar 2. Kromhout D, Giltay EJ, Geleijnse JM.Alpha Omega Trial Group. n-3 fatty acids and cardiovascular events after myocardial infarction. N Engl J Med. 2010;363(21):2015-202620929341PubMedGoogle ScholarCrossref 3. Burr ML, Fehily AM, Gilbert JF, et al. Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART). Lancet. 1989;2(8666):757-7612571009PubMedGoogle Scholar 4. Marchioli R, Schweiger C, Tavazzi L, Valagussa F.Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico. Efficacy of n-3 polyunsaturated fatty acids after myocardial infarction: results of GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico. Lipids. 2001;36:(suppl) S119-S12611837985PubMedGoogle Scholar 5. Yokoyama M, Origasa H, Matsuzaki M, et al; Japan EPA lipid intervention study (JELIS) Investigators. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet. 2007;369(9567):1090-109817398308PubMedGoogle Scholar http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Archives of Internal Medicine American Medical Association

The Big Ones That Got Away: Omega-3 Meta-analysis Flawed by Excluding the Biggest Fish Oil Trials—Reply

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References (6)

Publisher
American Medical Association
Copyright
Copyright © 2012 American Medical Association. All Rights Reserved.
ISSN
0003-9926
eISSN
1538-3679
DOI
10.1001/archinternmed.2012.4300
Publisher site
See Article on Publisher Site

Abstract

In reply We appreciate the letter of DiNicolantonio et al in response to our report1 in the Archives. We acknowledge that several methodologic issues raised by DiNicolantonio et al are important for our main conclusions. First, regarding the small sample size and short follow-up period, we stated in the limitations of the “Comment” section1(p693) that Fifth, most trials included in the present meta-analysis had a small sample size of 59 to 500 participants and a short duration of treatment of less than 2 to 3 years. Further larger trials are needed. However, although we included trials with a small sample size of participants, the number of total participants in the meta-analysis was more than 20 000, which is regarded as having enough power to detect a difference in cardiovascular outcomes. Second, regarding the exclusion of the 5 trials with the use of olive oil as a control group, when we performed a subgroup meta-analysis with excluding those 5 trials, no preventive effect of omega-3 fatty acid supplementation on overall cardiovascular events was observed (relative risk [RR], 0.94; 95% CI, 0.83-1.07). Also, when we performed a meta-analysis without the trial by Kromhout et al2 that used margarine spread, there was no preventive effect (RR, 0.98; 95% CI, 0.86-1.11). Third, the Diet and Reinfarction Trial (DART)3 that DiNicolantonio et al mentioned is not a relevant trial for our meta-analysis because it used only advice on an increase in fatty fish intake, not omega-3 fatty acid supplementation. Last, regarding the exclusion of the Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico (GISSI)-Prevenzione4 and Japan Eicosapentaenoic Acid Lipid Intervention Study (JELIS)5 in our analysis, we already addressed in the “Comment” section. Again, the main reason that we excluded those 2 large randomized controlled trials is that they used an open-label design without using placebos, which is liable to performance bias. For the readers who have the same question, in our article1(p691) we already mentioned that When we performed a meta-analysis with the GISSI-Prevenzione trial[4] and the JELIS[5] in addition to the 14 trials included in the present study, a preventive effect of omega-3 fatty acid supplementation was not observed (RR, 0.95; 95% CI, 0.87-1.03; I2=35.5%) (data not shown). In conclusion, despite some methodologic issues and limitations, our meta-analysis indicates that there is a lack of sufficient evidence of the secondary preventive effects of omega-3 supplementation on cardiovascular disease. Further larger randomized, double-blind, placebo-controlled trials are needed to confirm our findings. Back to top Article Information Correspondence: Dr Myung, Carcinogenesis Branch, National Cancer Center, 323 Ilsan-ro, Ilsandong-gu, Goyang, Gyeonggi 410-769, Republic of Korea (msk@ncc.re.kr). Financial Disclosure: None reported. References 1. Kwak SM, Myung SK, Lee YJ, Seo HG.Korean Meta-analysis Study Group. Efficacy of omega-3 fatty acid supplements (eicosapentaenoic acid and docosahexaenoic acid) in the secondary prevention of cardiovascular disease: a meta-analysis of randomized, double-blind, placebo-controlled trials. Arch Intern Med. 2012;172(9):686-69422493407PubMedGoogle Scholar 2. Kromhout D, Giltay EJ, Geleijnse JM.Alpha Omega Trial Group. n-3 fatty acids and cardiovascular events after myocardial infarction. N Engl J Med. 2010;363(21):2015-202620929341PubMedGoogle ScholarCrossref 3. Burr ML, Fehily AM, Gilbert JF, et al. Effects of changes in fat, fish, and fibre intakes on death and myocardial reinfarction: diet and reinfarction trial (DART). Lancet. 1989;2(8666):757-7612571009PubMedGoogle Scholar 4. Marchioli R, Schweiger C, Tavazzi L, Valagussa F.Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico. Efficacy of n-3 polyunsaturated fatty acids after myocardial infarction: results of GISSI-Prevenzione trial. Gruppo Italiano per lo Studio della Sopravvivenza nell’Infarto Miocardico. Lipids. 2001;36:(suppl) S119-S12611837985PubMedGoogle Scholar 5. Yokoyama M, Origasa H, Matsuzaki M, et al; Japan EPA lipid intervention study (JELIS) Investigators. Effects of eicosapentaenoic acid on major coronary events in hypercholesterolaemic patients (JELIS): a randomised open-label, blinded endpoint analysis. Lancet. 2007;369(9567):1090-109817398308PubMedGoogle Scholar

Journal

Archives of Internal MedicineAmerican Medical Association

Published: Oct 8, 2012

Keywords: omega-3 fatty acids,fish oils

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