Kastelein John J P, Maki Kevin C, Susekov Andrey, Ezhov Marat, Nordestgaard Borge G, Machielse Ben N, Kling Douglas, Davidson Michael H
Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, 1105 AZ, Amsterdam, The Netherlands.
Biofortis Clinical Research, Addison, IL, USA.
J Clin Lipidol. 2014 Jan-Feb;8(1):94-106. doi: 10.1016/j.jacl.2013.10.003. Epub 2013 Oct 14.
Omega-3 fatty acids in free fatty acid form have enhanced bioavailability, and plasma levels are less influenced by food than for ethyl ester forms.
The aim was to evaluate the safety and lipid-altering efficacy in subjects with severe hypertriglyceridemia of an investigational pharmaceutical omega-3 free fatty acid (OM3-FFA) containing eicosapentaenoic acid and docosahexaenoic acid.
This was a multinational, double-blind, randomized, out-patient study. Men and women with triglycerides (TGs) ≥ 500 mg/dL, but <2000 mg/dL, took control (olive oil [OO] 4 g/d; n = 99), OM3-FFA 2 g/d (plus OO 2 g/d; n = 100), OM3-FFA 3 g/d (plus OO 1 g/d; n = 101), or OM3-FFA 4 g/d (n = 99) capsules for 12 weeks in combination with the National Cholesterol Education Program Therapeutic Lifestyle Changes diet.
Fasting serum TGs changed from baseline by -25.9% (P < .01 vs OO), -25.5% (P < .01 vs OO), and -30.9% (P < .001 vs OO) with 2, 3, and 4 g/d OM3-FFA, respectively, compared with -4.3% with OO. Non-high-density lipoprotein cholesterol (non-HDL-C), total cholesterol-to-HDL-C ratio, very low-density lipoprotein cholesterol, remnant-like particle cholesterol, apolipoprotein CIII, lipoprotein-associated phospholipase A2, and arachidonic acid were significantly lowered (P < .05 at each OM3-FFA dosage vs OO); and plasma eicosapentaenoic acid and docosahexaenoic acid were significantly elevated (P < .001 at each OM3-FFA dosage vs OO). With OM3-FFA 2 and 4 g/d (but not 3 g/d), low-density lipoprotein cholesterol was significantly increased compared with OO (P < .05 vs OO). High-sensitivity C-reactive protein responses with OM3-FFA did not differ significantly from the OO response at any dosage. Fewer subjects reported any adverse event with OO vs OM3-FFA, but frequencies across dosage groups were similar. Discontinuation due to adverse event, primarily gastrointestinal, ranged from 5% to 7% across OM3-FFA dosage groups vs 0% for OO.
OM3-FFA achieved the primary end point for TG lowering and secondary end point of non-HDL-C lowering at 2, 3, and 4 g/d in persons with severe hypertriglyceridemia. This trial was registered at www.clinicaltrials.gov as NCT01242527.
游离脂肪酸形式的ω-3脂肪酸具有更高的生物利用度，与乙酯形式相比，其血浆水平受食物的影响较小。
评估一种含有二十碳五烯酸和二十二碳六烯酸的研究用ω-3游离脂肪酸（OM3-FFA）对重度高甘油三酯血症患者的安全性和血脂改变疗效。
这是一项多国、双盲、随机、门诊研究。甘油三酯（TGs）≥500mg/dL但<2000mg/dL的男性和女性，服用对照物（橄榄油[OO]4g/d；n = 99）、OM3-FFA 2g/d（加OO 2g/d；n = 100）、OM3-FFA 3g/d（加OO 1g/d；n = 101）或OM3-FFA 4g/d（n = 99）胶囊，为期12周，并结合美国国家胆固醇教育计划治疗性生活方式改变饮食。
空腹血清TGs与基线相比，服用2、3和4g/d OM3-FFA时分别变化了-25.9%（与OO相比P <.01）、-25.5%（与OO相比P <.01）和-30.9%（与OO相比P <.001）, 而服用OO时变化了-4.3%。非高密度脂蛋白胆固醇（non-HDL-C）、总胆固醇与HDL-C比值、极低密度脂蛋白胆固醇、残粒样颗粒胆固醇、载脂蛋白CIII、脂蛋白相关磷脂酶A2和花生四烯酸均显著降低（各OM3-FFA剂量组与OO相比P <.05）；血浆二十碳五烯酸和二十二碳六烯酸显著升高（各OM3-FFA剂量组与OO相比P <.001）。服用2g/d和4g/d（而非3g/d）OM3-FFA时，低密度脂蛋白胆固醇与OO相比显著升高（与OO相比P <.05）。各剂量的OM3-FFA组高敏C反应蛋白反应与OO组相比无显著差异。报告有任何不良事件的受试者，OO组比OM3-FFA组少，但各剂量组的频率相似。因不良事件（主要为胃肠道不良事件）停药的比例，OM3-FFA各剂量组为5%至7%，而OO组为0%。
重度高甘油三酯血症患者服用2、3和4g/d的OM3-FFA达到了降低TG的主要终点和降低non-HDL-C的次要终点。该试验在www.clinicaltrials.gov上注册，注册号为NCT01242527。
