Zhang Weiguo, Gan Dan, Huo Shaofeng, Chen Peng
Las Colinas Institutes, Irving, TX, United States.
R&D, Sirio Life Technology Co., Ltd, Shanghai, China.
Front Nutr. 2024 Dec 19;11:1490953. doi: 10.3389/fnut.2024.1490953. eCollection 2024.
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.
两项大规模、随机、双盲、安慰剂对照试验——REDUCE - IT和STRENGTH——在心血管医学领域引起了广泛关注。这两项试验均旨在评估长期给予营养性脂质，特别是ω-3脂肪酸，对接受他汀类药物治疗的高危患者主要不良心血管事件（MACE）的影响。REDUCE - IT使用二十碳五烯酸（EPA）乙酯并以矿物油作为对照，而STRENGTH使用EPA和二十二碳六烯酸（DHA）的羧酸制剂并以玉米油作为对照。值得注意的是，REDUCE - IT证明EPA可降低MACE风险，而STRENGTH显示EPA与DHA联合使用并无此益处。尽管在这些试验发表后进行了广泛且有深度的讨论，但这种差异的根本原因仍不清楚。我们认为，对静息心率（RHR）、心率变异性（HRV）以及收集但未充分探索的种族亚组数据进行进一步研究，对于阐明REDUCE - IT和STRENGTH试验结果的差异至关重要。这些额外的分析可能为驱动ω-3脂肪酸在高危心血管患者中产生不同作用的机制提供关键见解。鉴于之前的讨论尚未充分涉及这些潜在变量，对其进行探索可能会揭示未被探索的途径，并更深入地理解ω-3脂肪酸在心血管健康中的机制和临床作用。我们假设，通过深入研究这些分析不足的因素，我们不仅可以澄清试验之间的差异，还能推进我们对心血管营养和医学的更广泛理解。
