In patients with severe hypertriglyceridemia (HTG), the use of ω-3 phospholipid/free fatty acid (PL/FFA)—a novel krill oil–derived ω-3 formulation—reduced triglyceride (TG) levels. Study results were published in JAMA Network Open.
The investigators sought to establish the efficacy and safety of a naturally derived krill oil in patients with severe HTG by measuring TG levels and other lipid parameters.
For the current study, researchers pooled the results of 2 identical randomized, double-blind, placebo-controlled, phase 3 trials—Study of CaPre in Lowering Very High Triglycerides (TRILOGY 1 [ClinicalTrials.gov identifier: NCT03398005] and TRILOGY 2 [ClinicalTrials.gov identifier: NCT03361501]). TRILOGY 1 enrolled participants from 71 US centers between January 23, 2018, and November 20, 2019. TRILOGY 2 enrolled participants from 93 US, Canadian, and Mexican centers between April 6, 2018, and January 9, 2020. Patients enrolled in the study had fasting TG levels between 500 and 1500 mg/dL, regardless of stable treatment with statins, fibrates, or other agents for lowering cholesterol levels.
The primary outcome was mean percentage of change in TG levels at 12 weeks; the main secondary outcome was persistence at 26 weeks. Other prespecified secondary outcomes included effects on non-high-density lipoprotein cholesterol (non-HDL-C), very-low-density lipoprotein cholesterol (VLDL-C), HDL-C, and low-density lipoprotein cholesterol (LDL-C) levels. A total of 520 participants were randomly assigned 2.5 to 1.0 to ω-3-PL/FFA (n=372) or placebo (n=148) for 26 weeks.
The mean participant age was 54.9±11.2 years. Overall, 65.2% of the patients were men and 34.8% were women. Mean body mass index (BMI) was 31.5. The baseline mean TG level was 701 mg/dL, with 32.3% of the participants having a TG level of greater than 750 mg/dL. A total of 256 patients were Hispanic or Latino,275 had diabetes, and 248 were being treated with statins.
Study results showed that at 12 weeks, TG levels decreased by 26.0% in the ω-3-PL/FFA group (95% CI, 20.5% to 31.5%) vs 15.1% in the placebo group (95% CI, 6.6% to 23.5%) (mean treatment difference, -10.9%; 95% CI, -20.4% to -1.5%; P=.02). This treatment difference persisted at 26 weeks, with TG levels decreased by 33.5% in the ω-3-PL/FFA group (95%% CI, 27.2% to 39.8%) compared with 20.8% in the placebo group (95% CI, 11.5% to 30.1%) (mean treatment difference, -12.7%; 95% CI, -23.1% to -2.4%; P=.02).
At 12 weeks, the use of ω-3-PL/FFA had no statistically significant effects compared with placebo on mean treatment differences in non-HDL-C, VLDL-C, HDL-C, or LDL-C levels. At 26 weeks, corresponding differences were as follows: non-HDL-C levels (-5.8%; 95% CI, -11.3% to -0.3%; P=.04); VLDL-C levels (-9.1%; 95% CI, -21.5% to 3.2%; P=.15); HDL-C levels (1.9%; 95% CI, -4.8% to 8.6%; P=.57); and LDL-C levels (6.3%; 95% CI, -12.4% to 25.0%; P=.51).
Although the effects on the primary endpoint did not differ significantly by sex, age, race and ethnicity, country, qualifying TG level, presence of diabetes, or fibrate use, the effect was larger among participants being treated with statins or cholesterol absorption inhibitors at baseline (mean treatment difference, -19.5%; 95% CI, -34.5% to -4.6%; P=.08 for interaction) and with lower baseline blood eicosapentaenoic acid plus docosahexaenoic acid levels (mean treatment difference, -19.5%; 95% CI, -33.8% to -5.3%; P=.08 for interaction).
The investigators noted that ω-3–PL/FFA “reduce[s] TG levels at 12 and 26 weeks and increase[s] the proportion of patients with TG levels of less than 500 mg/dL” among patients with severe hypertriglyceridemia. They also stated, “The treatment [is] safe and well tolerated.”
Disclosure: Some of the study authors have declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.
Mozaffarian D, Maki KC, Bays HE, et al. Effectiveness of a novel ω-3 krill oil agent in patients with severe hypertriglyceridemia: a randomized clinical trial. JAMA Netw Open. Published online January 6, 2022. doi:10.1001/jamanetworkopen.2021.41898