Unraveling the discrepancies between REDUCE-IT and STRENGTH trials with omega-3 fatty acids: new analytical approaches

Two large-scale, randomized, double-blind, placebo-controlled trials—REDUCE-IT and STRENGTH—have garnered significant attention in cardiovascular medicine. Both trials aimed to evaluate the effects of prolonged administration of nutritional lipids, specifically omega-3 fatty acids, on major adverse...

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Main Authors: Weiguo Zhang, Dan Gan, Shaofeng Huo, Peng Chen
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-12-01
Series:Frontiers in Nutrition
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Online Access:https://www.frontiersin.org/articles/10.3389/fnut.2024.1490953/full
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author Weiguo Zhang
Dan Gan
Shaofeng Huo
Peng Chen
author_facet Weiguo Zhang
Dan Gan
Shaofeng Huo
Peng Chen
author_sort Weiguo Zhang
collection DOAJ
description Two large-scale, randomized, double-blind, placebo-controlled trials—REDUCE-IT and STRENGTH—have garnered significant attention in cardiovascular medicine. Both trials aimed to evaluate the effects of prolonged administration of nutritional lipids, specifically omega-3 fatty acids, on major adverse cardiovascular events (MACEs) in high-risk patients undergoing statin therapy. REDUCE-IT used eicosapentaenoic acid (EPA) ethyl ester with mineral oil as a control, while STRENGTH utilized a carboxylic acid formulation of both EPA and docosahexaenoic acid (DHA) with corn oil as a control. Notably, REDUCE-IT demonstrated a reduction in MACE risk with EPA, whereas STRENGTH showed no such benefit with the combination of EPA and DHA. Despite extensive and insightful discussions following the publication of these trials, the underlying reasons for this discrepancy remain elusive. We posit that further investigation into resting heart rate (RHR), heart rate variability (HRV), and ethnic subgroup data—collected but not fully explored—is critical to unraveling the divergent outcomes of the REDUCE-IT and STRENGTH trials. These additional analyses could provide pivotal insights into the mechanisms driving the differential effects of omega-3 fatty acids in high-risk cardiovascular patients. Given that previous discussions have not fully addressed these potential variables, exploring them may illuminate unexplored pathways and offer a deeper understanding of the mechanistic and clinical roles of omega-3 s in cardiovascular health. We hypothesize that by delving into these under-analyzed factors, we can not only clarify the discrepancies between the trials but also advance our broader understanding of cardiovascular nutrition and medicine.
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spelling doaj-art-a8f029f3c2eb4267a02debec5f4f9f982025-08-20T02:34:49ZengFrontiers Media S.A.Frontiers in Nutrition2296-861X2024-12-011110.3389/fnut.2024.14909531490953Unraveling the discrepancies between REDUCE-IT and STRENGTH trials with omega-3 fatty acids: new analytical approachesWeiguo Zhang0Dan Gan1Shaofeng Huo2Peng Chen3Las Colinas Institutes, Irving, TX, United StatesR&D, Sirio Life Technology Co., Ltd, Shanghai, ChinaR&D, Sirio Life Technology Co., Ltd, Shanghai, ChinaR&D, Sirio Pharma Co., Ltd, Shantou, Guangdong, ChinaTwo large-scale, randomized, double-blind, placebo-controlled trials—REDUCE-IT and STRENGTH—have garnered significant attention in cardiovascular medicine. Both trials aimed to evaluate the effects of prolonged administration of nutritional lipids, specifically omega-3 fatty acids, on major adverse cardiovascular events (MACEs) in high-risk patients undergoing statin therapy. REDUCE-IT used eicosapentaenoic acid (EPA) ethyl ester with mineral oil as a control, while STRENGTH utilized a carboxylic acid formulation of both EPA and docosahexaenoic acid (DHA) with corn oil as a control. Notably, REDUCE-IT demonstrated a reduction in MACE risk with EPA, whereas STRENGTH showed no such benefit with the combination of EPA and DHA. Despite extensive and insightful discussions following the publication of these trials, the underlying reasons for this discrepancy remain elusive. We posit that further investigation into resting heart rate (RHR), heart rate variability (HRV), and ethnic subgroup data—collected but not fully explored—is critical to unraveling the divergent outcomes of the REDUCE-IT and STRENGTH trials. These additional analyses could provide pivotal insights into the mechanisms driving the differential effects of omega-3 fatty acids in high-risk cardiovascular patients. Given that previous discussions have not fully addressed these potential variables, exploring them may illuminate unexplored pathways and offer a deeper understanding of the mechanistic and clinical roles of omega-3 s in cardiovascular health. We hypothesize that by delving into these under-analyzed factors, we can not only clarify the discrepancies between the trials but also advance our broader understanding of cardiovascular nutrition and medicine.https://www.frontiersin.org/articles/10.3389/fnut.2024.1490953/fullmajor adverse cardiovascular events (MACEs)residual cardiovascular risk (RCR)eicosapentaenoic acid (EPA)docosahexaenoic acid (DHA)resting heart rate (RHR)heart rate variability (HRV)
spellingShingle Weiguo Zhang
Dan Gan
Shaofeng Huo
Peng Chen
Unraveling the discrepancies between REDUCE-IT and STRENGTH trials with omega-3 fatty acids: new analytical approaches
Frontiers in Nutrition
major adverse cardiovascular events (MACEs)
residual cardiovascular risk (RCR)
eicosapentaenoic acid (EPA)
docosahexaenoic acid (DHA)
resting heart rate (RHR)
heart rate variability (HRV)
title Unraveling the discrepancies between REDUCE-IT and STRENGTH trials with omega-3 fatty acids: new analytical approaches
title_full Unraveling the discrepancies between REDUCE-IT and STRENGTH trials with omega-3 fatty acids: new analytical approaches
title_fullStr Unraveling the discrepancies between REDUCE-IT and STRENGTH trials with omega-3 fatty acids: new analytical approaches
title_full_unstemmed Unraveling the discrepancies between REDUCE-IT and STRENGTH trials with omega-3 fatty acids: new analytical approaches
title_short Unraveling the discrepancies between REDUCE-IT and STRENGTH trials with omega-3 fatty acids: new analytical approaches
title_sort unraveling the discrepancies between reduce it and strength trials with omega 3 fatty acids new analytical approaches
topic major adverse cardiovascular events (MACEs)
residual cardiovascular risk (RCR)
eicosapentaenoic acid (EPA)
docosahexaenoic acid (DHA)
resting heart rate (RHR)
heart rate variability (HRV)
url https://www.frontiersin.org/articles/10.3389/fnut.2024.1490953/full
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