Omega-3 free fatty acids for the treatment of severe hypertriglyceridemia: The EpanoVa fOr Lowering Very high triglyceridEs (EVOLVE) trial
Open accessAbstract
Background 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.Objective 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.Methods 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.Results 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.Conclusions 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.
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- Findingown data§ Discussion
The regression-predicted triglyceride reductions of 32.8% and 38.4% were similar to the observed least-squares geometric mean reductions of 30.9% and 44.3%.
“These values are similar to the observed LSGM reductions of 30.9% and 44.3%, respectively.”
Quote in the paperNot a substantial claim- Rests on an assumption: Olive oil 4 g/d is an inert control that does not itself meaningfully alter triglycerides or non-HDL-C, so differences from olive oil can be attributed to OM3-FFA.
- Rests on an assumption: Subjects adhered to the TLC diet and maintained weight during the trial, so observed lipid changes are not due to diet or weight changes.
- Findingown data§ Results
OM3-FFA at 2, 3, and 4 g/d significantly reduced VLDL-C compared with olive oil.
“Non-HDL-C, total-Cto-HDL-C ratio, VLDL-C, RLP-C, and Apo CIII concentrations were also significantly reduced in each OM3-FFA treatment group compared with responses in the OO group.”
Quote in the paperSubstantial claim- Rests on an assumption: Olive oil 4 g/d is an inert control that does not itself meaningfully alter triglycerides or non-HDL-C, so differences from olive oil can be attributed to OM3-FFA.
- Rests on an assumption: Subjects adhered to the TLC diet and maintained weight during the trial, so observed lipid changes are not due to diet or weight changes.
- Findingown data§ Results
Plasma DHA and EPA increased significantly in all OM3-FFA groups compared with olive oil.
“plasma DHA and EPA concentrations increased significantly, and AA concentrations were reduced significantly in all OM3-FFA treatment groups compared with the OO group (all P , .001).”
Quote in the paperNot a substantial claim- Rests on an assumption: Olive oil 4 g/d is an inert control that does not itself meaningfully alter triglycerides or non-HDL-C, so differences from olive oil can be attributed to OM3-FFA.
- Rests on an assumption: Subjects adhered to the TLC diet and maintained weight during the trial, so observed lipid changes are not due to diet or weight changes.
- Findingown data§ Results
Apo AI increased more with olive oil than with OM3-FFA 2 or 4 g/d.
“Apo AI concentration was increased in the OO group compared with responses to the 2 and 4 g/d OM3-FFA groups (P ,.01).”
Quote in the paperNot a substantial claim- Rests on an assumption: Olive oil 4 g/d is an inert control that does not itself meaningfully alter triglycerides or non-HDL-C, so differences from olive oil can be attributed to OM3-FFA.
- Rests on an assumption: Subjects adhered to the TLC diet and maintained weight during the trial, so observed lipid changes are not due to diet or weight changes.
- Findingown data§ Results
Total-C was significantly reduced versus olive oil in the 2 and 4 g/d OM3-FFA groups.
“Total-C was reduced in all OM3-FFA treatment groups.Comparisons of the 2-and 4-g/d treatment groups vs OO showed statistical significance.”
Quote in the paperNot a substantial claim- Rests on an assumption: Olive oil 4 g/d is an inert control that does not itself meaningfully alter triglycerides or non-HDL-C, so differences from olive oil can be attributed to OM3-FFA.
- Rests on an assumption: Subjects adhered to the TLC diet and maintained weight during the trial, so observed lipid changes are not due to diet or weight changes.
- Findingown data§ Results
OM3-FFA did not significantly change HDL-C relative to olive oil at any tested dose.
“HDL-C increased slightly in all treatment groups, but no significant differences were found between the OO and OM3-FFA responses.”
- Also stated in: § Discussion · plain
“whereas HDL-C was not significantly changed vs OO with OM3-FFA at any dosage.”
Quote in the paperNot a substantial claim- Rests on an assumption: Olive oil 4 g/d is an inert control that does not itself meaningfully alter triglycerides or non-HDL-C, so differences from olive oil can be attributed to OM3-FFA.
- Rests on an assumption: Subjects adhered to the TLC diet and maintained weight during the trial, so observed lipid changes are not due to diet or weight changes.
- Also stated in: § Discussion · plain
- Findingown data§ Results
OM3-FFA at 2, 3, and 4 g/d significantly reduced Apo CIII compared with olive oil.
“Non-HDL-C, total-Cto-HDL-C ratio, VLDL-C, RLP-C, and Apo CIII concentrations were also significantly reduced in each OM3-FFA treatment group compared with responses in the OO group.”
Quote in the paperNot a substantial claim- Rests on an assumption: Olive oil 4 g/d is an inert control that does not itself meaningfully alter triglycerides or non-HDL-C, so differences from olive oil can be attributed to OM3-FFA.
- Rests on an assumption: Subjects adhered to the TLC diet and maintained weight during the trial, so observed lipid changes are not due to diet or weight changes.
- Findingown data§ Results
Plasma arachidonic acid decreased significantly in all OM3-FFA groups compared with olive oil.
“plasma DHA and EPA concentrations increased significantly, and AA concentrations were reduced significantly in all OM3-FFA treatment groups compared with the OO group (all P , .001).”
Quote in the paperNot a substantial claim- Rests on an assumption: Olive oil 4 g/d is an inert control that does not itself meaningfully alter triglycerides or non-HDL-C, so differences from olive oil can be attributed to OM3-FFA.
- Rests on an assumption: Subjects adhered to the TLC diet and maintained weight during the trial, so observed lipid changes are not due to diet or weight changes.
- Findingown data§ Results
Apo B did not differ significantly between any OM3-FFA dose and olive oil.
“Apo B responses in each of the OM3-FFA groups were not significantly different than the OO response”
Quote in the paperNot a substantial claim- Rests on an assumption: Olive oil 4 g/d is an inert control that does not itself meaningfully alter triglycerides or non-HDL-C, so differences from olive oil can be attributed to OM3-FFA.
- Rests on an assumption: Subjects adhered to the TLC diet and maintained weight during the trial, so observed lipid changes are not due to diet or weight changes.
- Findingown data§ Discussion
Serum Apo CIII was lowered by 11%, 12%, and 14% with OM3-FFA 2, 3, and 4 g/d, respectively, versus a 2% increase with olive oil.
“In the present trial, serum Apo CIII was lowered by 11%, 12%, and 14% with OM3-FFA dosages of 2, 3, and 4 g/d, respectively, compared with a 2% increase with OO.”
Quote in the paperNot a substantial claim- Rests on an assumption: Olive oil 4 g/d is an inert control that does not itself meaningfully alter triglycerides or non-HDL-C, so differences from olive oil can be attributed to OM3-FFA.
- Rests on an assumption: Subjects adhered to the TLC diet and maintained weight during the trial, so observed lipid changes are not due to diet or weight changes.
- Findingown data§ Results
hs-CRP did not differ significantly from olive oil at any OM3-FFA dose.
“hs-CRP responses with OM3-FFA did not differ significantly from the OO response at any dosage.”
Quote in the paperNot a substantial claim- Rests on an assumption: Olive oil 4 g/d is an inert control that does not itself meaningfully alter triglycerides or non-HDL-C, so differences from olive oil can be attributed to OM3-FFA.
- Rests on an assumption: Subjects adhered to the TLC diet and maintained weight during the trial, so observed lipid changes are not due to diet or weight changes.
- Findingown data§ Conclusions
In adults with severe hypertriglyceridemia, OM3-FFA at 2, 3, and 4 g/d lowered fasting serum triglycerides from baseline more than olive oil 4 g/d over 12 weeks.
“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.”
- Also stated in: § Discussion · plain
“OM3-FFA at 2-, 3-, and 4-g/d dosages significantly reduced TG levels from baseline by 25.9%, 25.5%, and 30.9%, respectively, compared with a 4.3% decline in subjects taking 4 g/d OO.”
Quote in the paperSubstantial claim- Rests on an assumption: Olive oil 4 g/d is an inert control that does not itself meaningfully alter triglycerides or non-HDL-C, so differences from olive oil can be attributed to OM3-FFA.
- Rests on an assumption: Subjects adhered to the TLC diet and maintained weight during the trial, so observed lipid changes are not due to diet or weight changes.
- Also stated in: § Discussion · plain
- Findingown data§ Results
Gastrointestinal adverse events were more frequent in OM3-FFA groups than in the olive oil group.
“Gastrointestinal events were reported with higher frequencies in the OM3-FFA groups (19.0%-27.3%)than in the OO group (7.1%).”
Quote in the paperNot a substantial claim - Findingown data§ Results
OM3-FFA at 2, 3, and 4 g/d significantly reduced RLP-C compared with olive oil.
“Non-HDL-C, total-Cto-HDL-C ratio, VLDL-C, RLP-C, and Apo CIII concentrations were also significantly reduced in each OM3-FFA treatment group compared with responses in the OO group.”
Quote in the paperNot a substantial claim- Rests on an assumption: Olive oil 4 g/d is an inert control that does not itself meaningfully alter triglycerides or non-HDL-C, so differences from olive oil can be attributed to OM3-FFA.
- Rests on an assumption: Subjects adhered to the TLC diet and maintained weight during the trial, so observed lipid changes are not due to diet or weight changes.
- Findingown data§ Results
Treatment-emergent adverse events occurred more often in OM3-FFA groups than in the olive oil group.
“The frequencies of 1 or more treatment-emergent AEs were OO (26.3%),OM3-FFA 2 g/d (40.0%),OM3-FFA 3 g/d (42.6%), and OM3-FFA 4 g/d (44.4%) (P 5 .036).”
Quote in the paperNot a substantial claim - Findingown data§ Results
The change in LDL-C-to-Apo B ratio was significantly greater with OM3-FFA 4 g/d than with olive oil.
“the change in LDL-C-to-Apo B ratio was significantly greater in the OM3-FFA 4 g/d group (17.8%) vs the OO group (4.1%) (P ,.01).”
Quote in the paperNot a substantial claim- Rests on an assumption: Olive oil 4 g/d is an inert control that does not itself meaningfully alter triglycerides or non-HDL-C, so differences from olive oil can be attributed to OM3-FFA.
- Rests on an assumption: Subjects adhered to the TLC diet and maintained weight during the trial, so observed lipid changes are not due to diet or weight changes.
- Findingown data§ Results
Discontinuation because of adverse events, mainly gastrointestinal, occurred in 5% to 7% of OM3-FFA groups and 0% of the olive oil group.
“Discontinuation due to AEs, primarily gastrointestinal, ranged from 5% to 7% across dosage groups vs 0% for the OO group.”
Quote in the paperNot a substantial claim - Findingown data§ Conclusions
In the same trial, OM3-FFA at 2, 3, and 4 g/d lowered non-HDL-C from baseline more than olive oil 4 g/d.
“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.”
- Also stated in: § Discussion · plain
“Non-HDL-C was also significantly lowered in each of the active treatment groups by 6.9% to 9.6%, compared with an increase of 2.5% in the OO group, whereas HDL-C was not significantly changed vs OO with OM3-FFA at any dosage.”
Quote in the paperNot a substantial claim- Rests on an assumption: Olive oil 4 g/d is an inert control that does not itself meaningfully alter triglycerides or non-HDL-C, so differences from olive oil can be attributed to OM3-FFA.
- Rests on an assumption: Subjects adhered to the TLC diet and maintained weight during the trial, so observed lipid changes are not due to diet or weight changes.
- Also stated in: § Discussion · plain
- Findingown data§ Results
OM3-FFA at 2, 3, and 4 g/d significantly reduced the total-C-to-HDL-C ratio compared with olive oil.
“Non-HDL-C, total-Cto-HDL-C ratio, VLDL-C, RLP-C, and Apo CIII concentrations were also significantly reduced in each OM3-FFA treatment group compared with responses in the OO group.”
Quote in the paperNot a substantial claim- Rests on an assumption: Olive oil 4 g/d is an inert control that does not itself meaningfully alter triglycerides or non-HDL-C, so differences from olive oil can be attributed to OM3-FFA.
- Rests on an assumption: Subjects adhered to the TLC diet and maintained weight during the trial, so observed lipid changes are not due to diet or weight changes.
- Findingown data§ Discussion
More than 90% of participants were non-Hispanic and white.
“Greater than 90% of the participants were non-Hispanic and white”
Quote in the paperNot a substantial claim - Findingown data§ Conclusions
The same new EPA and DHA free fatty acid formulation significantly lowered non-HDL cholesterol concentrations at 2, 3, and 4 g/d.
“a novel formulation that contained free fatty acid forms of both EPA and DHA produced significant lowering of TGs and non-HDL-C concentrations at 2-, 3-, and 4-g/d dosages.”
Quote in the paperSubstantial claim- Rests on an assumption: The olive oil control does not itself alter the lipid or inflammatory endpoints, so differences from olive oil can be attributed to omega-3 free fatty acids.
- Findingown data§ Discussion
Mild-to-moderate gastrointestinal events, including diarrhea, eructation, and nausea, were the most frequently reported adverse events with omega-3 free fatty acids.
“Mild-to-moderate gastrointestinal events (diarrhea, eructation, and nausea) were the most commonly reported AEs in association with OM3-FFA treatment”
Quote in the paperNot a substantial claim - Findingown data§ Discussion
High-sensitivity C-reactive protein did not decrease with omega-3 free fatty acids relative to the olive oil control.
“hs-CRP was not reduced with OM3-FFA compared with OO.”
Quote in the paperNot a substantial claim - Findingown data§ Discussion
Three percent of discontinuations in the omega-3 free fatty acid groups were due to gastrointestinal adverse events.
“(3% of discontinuations in the OM3-FFA groups were because of gastrointestinal AEs)”
Quote in the paperNot a substantial claim - Findingown data§ Conclusions
A new formulation with EPA and DHA in free fatty acid form significantly lowered triglyceride concentrations at 2, 3, and 4 g/d.
“a novel formulation that contained free fatty acid forms of both EPA and DHA produced significant lowering of TGs and non-HDL-C concentrations at 2-, 3-, and 4-g/d dosages.”
Quote in the paperSubstantial claim- Rests on an assumption: The olive oil control does not itself alter the lipid or inflammatory endpoints, so differences from olive oil can be attributed to omega-3 free fatty acids.
- Findingown data§ Discussion
The proportions reporting any adverse event were similar across the omega-3 free fatty acid dose groups (40%, 43%, and 44% for 2, 3, and 4 g/d).
“but the frequencies across the OM3-FFA dosage groups were similar (40%, 43%, and 44% of subjects in 2-, 3-, and 4-g/d dosage groups, respectively).”
Quote in the paperSubstantial claim - Premisecitation§ Discussion
Elevated Apo CIII associated with Apo B-containing particles is an independent predictor of cardiovascular disease event risk.
“an elevated level of Apo CIII associated with Apo B-containing particles is an independent predictor of cardiovascular disease event risk, 49”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [49] Sacks, 2000, VLDL, apolipoproteins B, CIII, and E, and risk of recurrent coronary events in the Cholesterol and Recurrent Events (CARE) trial, Circulation source
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- Premisecitation§ Discussion
Non-HDL-C is a superior predictor of cardiovascular disease event risk compared with LDL-C.
“Non-HDL-C has been shown to be a superior predictor of cardiovascular disease event risk [36][37][38] compared with LDL-C”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [36][37][38]
Not checked in the free run.
- Interpretationreasoning§ Discussion
The net effect of OM3-FFA was to reduce cholesterol carried by atherogenic particles, as measured by non-HDL-C.
“the net effect was to reduce the amount of cholesterol carried by such particles (non-HDL-C), which is consistent with results from studies of EPA 1 DHA-EE.”
Quote in the paperSubstantial claim0 of 3 sources checked- cites [13] Pownall, 1999, Correlation of serum triglyceride and its reduction by omega-3 fatty acids with lipid transfer activity and the neutral lipid compositions of high-density and low-density lipoproteins, Atherosclerosis source
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- cites [34] Davidson, 2009, Effects of prescription omega-3-acid ethyl esters on lipoprotein particle concentrations, apolipoproteins AI and CIII, and lipoprotein-associated phospholipase A2 mass in statin-treated subjects with hypertriglyceridemia, J Clin Lipidol source
Not checked in the free run.
- cites [35] Maki, 2011, Effects of prescription omega-3-acid ethyl esters, coadministered with atorvastatin, on circulating levels of lipoprotein particles, apolipoprotein CIII and lipoprotein-associated phospholipase A2 mass in men and women with mixed dyslipidemia, J Clin Lipidol source
Not checked in the free run.
- Rests on an assumption: Olive oil 4 g/d is an inert control that does not itself meaningfully alter triglycerides or non-HDL-C, so differences from olive oil can be attributed to OM3-FFA.
- Rests on an assumption: Subjects adhered to the TLC diet and maintained weight during the trial, so observed lipid changes are not due to diet or weight changes.
- Interpretationreasoning§ Discussion
The authors do not believe the LDL-C increase with OM3-FFA would be expected to adversely affect cardiovascular disease risk.
“we do not believe that the increase in LDL-C would be expected to result in an adverse effect on cardiovascular disease risk”
Quote in the paperSubstantial claim- Rests on an assumption: Olive oil 4 g/d is an inert control that does not itself meaningfully alter triglycerides or non-HDL-C, so differences from olive oil can be attributed to OM3-FFA.
- Rests on an assumption: Subjects adhered to the TLC diet and maintained weight during the trial, so observed lipid changes are not due to diet or weight changes.
- Interpretationcitation§ Discussion
The Apo CIII reduction with OM3-FFA is consistent with prior findings of reduced Apo CIII after EPA plus DHA ingestion.
“This is consistent with prior findings of reduced Apo CIII after ingestion of EPA 1 DHA.”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [34] Davidson, 2009, Effects of prescription omega-3-acid ethyl esters on lipoprotein particle concentrations, apolipoproteins AI and CIII, and lipoprotein-associated phospholipase A2 mass in statin-treated subjects with hypertriglyceridemia, J Clin Lipidol source
Not checked in the free run.
- cites [35] Maki, 2011, Effects of prescription omega-3-acid ethyl esters, coadministered with atorvastatin, on circulating levels of lipoprotein particles, apolipoprotein CIII and lipoprotein-associated phospholipase A2 mass in men and women with mixed dyslipidemia, J Clin Lipidol source
Not checked in the free run.
- cites [48] Olivieri, 2005, Apolipoprotein C-III, n-3 polyunsaturated fatty acids, and “insulin-resistant” T-455C APOC3 gene polymorphism in heart disease patients: example of gene-diet interaction, Clin Chem source
Not checked in the free run.
- Rests on an assumption: Olive oil 4 g/d is an inert control that does not itself meaningfully alter triglycerides or non-HDL-C, so differences from olive oil can be attributed to OM3-FFA.
- Rests on an assumption: Subjects adhered to the TLC diet and maintained weight during the trial, so observed lipid changes are not due to diet or weight changes.
- Premisecitation§ Discussion
When non-HDL-C and LDL-C are discordant, risk appears to follow non-HDL-C rather than LDL-C.
“when the 2 measures are discordant, risk appears to follow non-HDL-C rather than LDL-C.38”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [38] Boekholdt, 2012, Association of LDL cholesterol, non-HDL cholesterol, and apolipoprotein B levels with risk of cardiovascular events among patients treated with statins: a meta-analysis, JAMA source
Not checked in the free run.
- Study design and conductnone given§ Discussion
The study was not powered to define the dose-response curve.
“This study was not powered to define the dose-response curve”
Quote in the paperNot a substantial claim - Premisecitation§ Introduction
Free fatty acid forms of omega-3 have up to fivefold greater apparent bioavailability than ethyl ester forms in head-to-head pharmacokinetic trials.
“Two head-to-head pharmacokinetic clinical trials have reported that free fatty acid forms of OM3s have up to 5-fold greater apparent bioavailability than EE forms.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [3][4][5]
Not checked in the free run.
- Interpretationown data§ Discussion
The high proportion of non-Hispanic white participants may restrict generalization of the results to other demographic groups.
“which may limit the generalizability of these results to other demographic groups.”
Quote in the paperNot a substantial claim - Interpretationcitation§ Discussion
The present trial suggests that omega-3 free fatty acids are better tolerated in the gastrointestinal tract than earlier uncoated capsule formulations.
“The present study indicates an improved gastrointestinal tolerability profile for OM3-FFA compared with free fatty acid formulations in uncoated gelatin capsules.3”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [3] Davidson, 2012, A novel omega-3 free fatty acid formulation has dramatically improved bioavailability during a low-fat diet compared with omega-3-acid ethyl esters: The ECLIPSE (Epanova® compared to Lovaza® in a pharmacokinetic single-dose evaluation) study, J Clin Lipidol source
Not checked in the free run.
- Study design and conductown data§ Discussion
A limitation of the trial was the relatively uniform ethnicity and race of enrolled subjects.
“A limitation of the present trial was the relatively uniform ethnicity/race profile of the subjects enrolled.”
Quote in the paperNot a substantial claim - Premisecitation§ Discussion
Long-chain polyunsaturated fatty acids compete with omega-3 fatty acids for liver desaturase enzymes that convert short-chain polyunsaturated fatty acids into long-chain polyunsaturated fatty acids.
“Long chain polyunsaturated fatty acids compete with OM3 fatty acids for the desaturase enzymes in the liver that facilitate conversion of short chain polyunsaturated fatty acids to long chain polyunsaturated fatty acids.[56][57][58]”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [56][57][58]
Not checked in the free run.
- Premisecitation§ Discussion
Earlier trials of EPA and DHA ethyl esters generally found no change in high-sensitivity C-reactive protein.
“In general, prior studies of EPA 1 DHA-EE treatments have reported no change in hs-CRP.34,35”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [34] Davidson, 2009, Effects of prescription omega-3-acid ethyl esters on lipoprotein particle concentrations, apolipoproteins AI and CIII, and lipoprotein-associated phospholipase A2 mass in statin-treated subjects with hypertriglyceridemia, J Clin Lipidol source
Not checked in the free run.
- cites [35] Maki, 2011, Effects of prescription omega-3-acid ethyl esters, coadministered with atorvastatin, on circulating levels of lipoprotein particles, apolipoprotein CIII and lipoprotein-associated phospholipase A2 mass in men and women with mixed dyslipidemia, J Clin Lipidol source
Not checked in the free run.
- Study design and conductnone given§ Conclusions
The trial was the largest double-blind, randomized, controlled study of a lipid-altering drug in patients with severe hypertriglyceridemia.
“In this trial, the largest double-blind, randomized, controlled investigation of a lipid-altering drug in patients with severe hypertriglyceridemia”
Quote in the paperNot a substantial claim - Premisecitation§ Discussion
The effect of omega-3 therapy adds to the effect of statin treatment.
“the effect of OM3 therapy is additive to that of statin treatment.34,35”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [34] Davidson, 2009, Effects of prescription omega-3-acid ethyl esters on lipoprotein particle concentrations, apolipoproteins AI and CIII, and lipoprotein-associated phospholipase A2 mass in statin-treated subjects with hypertriglyceridemia, J Clin Lipidol source
Not checked in the free run.
- cites [35] Maki, 2011, Effects of prescription omega-3-acid ethyl esters, coadministered with atorvastatin, on circulating levels of lipoprotein particles, apolipoprotein CIII and lipoprotein-associated phospholipase A2 mass in men and women with mixed dyslipidemia, J Clin Lipidol source
Not checked in the free run.
- Interpretationreasoning§ Discussion
Omega-3 free fatty acids lower arachidonic acid formation.
“Accordingly, OM3-FFA reduces the formation of AA”
Quote in the paperNot a substantial claim- Rests on an assumption: The olive oil control does not itself alter the lipid or inflammatory endpoints, so differences from olive oil can be attributed to omega-3 free fatty acids.
- May combine two claims. 22
- The quote only partly states this claim. 2
- Classified as probably not a substantial claim. 18
May combine two claims. The quote only partly states this claim.
Findingown data§ DiscussionLp-PLA2 was significantly lowered in all OM3-FFA groups, by about 11% to 17%, compared with about 2% with olive oil.
“Lp-PLA 2 , an enzyme that participates in inflammation and that has been shown to be an independent predictor of cardiovascular disease risk, 6,[52][53][54] was significantly lowered in all OM3-FFA treatment groups (changes from 211% to 217%) compared with the OO control group (22%).”
Quote in the paperNot a substantial claim- Rests on an assumption: Olive oil 4 g/d is an inert control that does not itself meaningfully alter triglycerides or non-HDL-C, so differences from olive oil can be attributed to OM3-FFA.
- Rests on an assumption: Subjects adhered to the TLC diet and maintained weight during the trial, so observed lipid changes are not due to diet or weight changes.
May combine two claims.
Findingown data§ ResultsLDL-C was significantly increased versus olive oil in the 2 and 4 g/d OM3-FFA groups, with about 19% increases versus 3% for olive oil.
“LDL-C was significantly increased, compared with OO, in the 2-g/d and 4-g/d OM3-FFA groups (3% for OO vs 19% for both 2 g/d [P , .01] and 4 g/d [P , .001]).”
Quote in the paperNot a substantial claim- Rests on an assumption: Olive oil 4 g/d is an inert control that does not itself meaningfully alter triglycerides or non-HDL-C, so differences from olive oil can be attributed to OM3-FFA.
- Rests on an assumption: Subjects adhered to the TLC diet and maintained weight during the trial, so observed lipid changes are not due to diet or weight changes.
May combine two claims. The quote only partly states this claim.
Findingown data§ ResultsLp-PLA2 declined significantly versus olive oil in every OM3-FFA group, with reductions of about 11% to 17%.
“Lp-PLA 2 declined significantly vs OO in each OM3-FFA treatment group (P , .01);changes in the OM3-FFA groups ranged from 211% to 217%.”
Quote in the paperNot a substantial claim- Rests on an assumption: Olive oil 4 g/d is an inert control that does not itself meaningfully alter triglycerides or non-HDL-C, so differences from olive oil can be attributed to OM3-FFA.
- Rests on an assumption: Subjects adhered to the TLC diet and maintained weight during the trial, so observed lipid changes are not due to diet or weight changes.
May combine two claims.
Findingown data§ DiscussionAdverse events leading to study discontinuation occurred at similar overall rates across omega-3 free fatty acid doses (5% to 7%) and at 0% with olive oil.
“The overall frequencies of AEs, inclusive of all types of events, leading to study discontinuation were similar across OM3-FFA dosages (5% to 7%) vs 0% for OO.”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown data§ DiscussionOmega-3 free fatty acids were safe and generally well tolerated.
“OM3-FFA was safe and generally well tolerated.”
Quote in the paperSubstantial claimMay combine two claims.
Findingown data§ DiscussionArachidonic acid fell by 15.1%, 16.0%, and 23.2% with 2, 3, and 4 g/d omega-3 free fatty acids, respectively, while it rose by 2.2% with olive oil.
“AA was reduced by 15.1%, 16.0%, and 23.2%, respectively, with the 2-, 3-, and 4-g/d dosages of OM3-FFA, compared with a 2.2% increase with OO.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Findingown data§ ResultsThe randomized subjects were predominantly white (92%) and men (77%), with mean age 51.5 years and BMI 31.2 kg/m2.
“The subjects were predominantly white (92%) and men (77%) with an average age of 51.5 years and body mass index of 31.2 kg/m 2 .”
Quote in the paperNot a substantial claimMay combine two claims.
Findingown data§ DiscussionAny adverse event was reported by 26% of the olive oil group, a lower proportion than in the omega-3 free fatty acid groups.
“Fewer subjects reported any AE with OO (26%) than with OM3-FFA”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Study design and conductown data§ Statistical analysesEfficacy comparisons used analysis of covariance with baseline values as covariates and a stratification factor for users and nonusers of permitted lipid-altering drugs.
“Efficacy end points for each OM3-FFA arm were compared with OO with the use of analysis of covariance with baseline values as covariates and a stratification factor for users and nonusers of permitted lipid-altering drugs”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductown data§ ResultsMean compliance with study product was 97.3%, with no marked differences between groups.
“Overall mean 6 SD compliance with study product was 97.3% 6 9.0% of expected doses, and no marked differences were observed in compliance between treatment groups.”
Quote in the paperNot a substantial claimClassified as probably not a substantial claim.
Study design and conductown data§ Statistical analysesThe targeted sample size of 332 gave at least 80% power to detect a 20% triglyceride difference versus olive oil, assuming a 35% standard deviation, two-sided alpha 0.05 with Bonferroni adjustment, and 10% attrition.
“The targeted sample size of 332 subjects (83 per treatment arm) was expected to provide at least 80% power to detect a difference of at least 20% in TG percentage changes compared with OO, assuming a common standard deviation (SD) in percentage change of 35%, a 2-sided a 5 0.05 adjusted for 3 pairwise tests vs OO (Bonferroni method), and 10% attrition rate.”
Quote in the paperSubstantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductown data§ Statistical analysesEfficacy results are reported from the modified intent-to-treat sample because per-protocol results did not differ materially.
“Only the results from the modified intent-to-treat sample are described herein because those from the per protocol sample did not differ materially.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductreasoning§ Statistical analysesThe sample size also gave 80% power to detect about 10% differences from olive oil in non-HDL-C and HDL-C, assuming a 17% standard deviation.
“This sample size was also expected to provide 80% power to detect approximately 10% differences from OO in percentage changes of non-HDL-C and HDL-C, assuming a common SD of 17% in each variable”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ DiscussionApo B is more predictive of coronary heart disease risk than LDL-C.
“Apo B has also been shown to be more predictive of risk of coronary heart disease than LDL-C.39”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [39] Sondermeijer, 2013, Non-HDL cholesterol vs. Apo B for risk of coronary heart disease in healthy individuals: the EPIC-Norfolk prospective population study, Eur J Clin Invest source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductown data§ Study designThe trial was double-blind, randomized, parallel, four-arm, with eight clinic visits at 74 sites.
“This was a double-blind, randomized, parallel, 4-arm study with 8 clinic visits conducted at 74 clinical sites”
Quote in the paperNot a substantial claimMay combine two claims.
Premisecitation§ DiscussionIn severe hypertriglyceridemia, baseline LDL-C is typically below average because a larger fraction of total cholesterol is carried in VLDL particles, partly due to inefficient triglyceride hydrolysis and reduced VLDL-to-LDL conversion.
“In severe hypertriglyceridemia the baseline LDL-C level is typically below average because a larger-than-normal fraction of total-C is carried in VLDL particles, in part because of inefficient TG hydrolysis and reduced rate of conversion of VLDL to LDL.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [31][32][33]
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown data§ Study designRandomization was stratified to balance treatment groups for use of allowed lipid-altering medications.
“A stratified randomization scheme was used to ensure that treatment groups were balanced for the use of other allowed lipid-altering medications”
Quote in the paperNot a substantial claimMay combine two claims.
Premisecitation§ DiscussionApo CIII inhibits lipoprotein lipase, slowing triglyceride hydrolysis, and interferes with hepatic Apo B/E receptor interactions, slowing removal of triglyceride-rich lipoproteins.
“Apo CIII appears to play an important role in the pathogenesis of hypertriglyceridemia, particularly for inhibiting the action of lipoprotein lipase, thus slowing TG hydrolysis.47 Apo CIII also interferes with the interactions of TG-rich lipoproteins with hepatic Apo B/E receptors, slowing the removal of these particles from the circulation.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [47] Kawakami, 2009, Apolipoprotein CIII links dyslipidemia with atherosclerosis, J Atheroscler Thromb source
Not checked in the free run.
May combine two claims.
Interpretationreasoning§ DiscussionThe LDL-C increase with OM3-FFA was not accompanied by a significant Apo B increase, and non-HDL-C, VLDL-C, and RLP-C were reduced, so the LDL-C increase was not associated with more circulating atherogenic lipoprotein particles.
“Thus, the increase in LDL-C with OM3-FFA was not associated with an increase in the circulating concentration of atherogenic lipoprotein particles”
Quote in the paperSubstantial claim- Rests on an assumption: Olive oil 4 g/d is an inert control that does not itself meaningfully alter triglycerides or non-HDL-C, so differences from olive oil can be attributed to OM3-FFA.
- Rests on an assumption: Subjects adhered to the TLC diet and maintained weight during the trial, so observed lipid changes are not due to diet or weight changes.
May combine two claims.
Study design and conductown data§ ResultsOf 399 randomly assigned subjects, 364 completed, with no significant difference in discontinuation among groups.
“Of the 399 persons randomly assigned to treatment, 364 completed the study.No significant differences were found among treatment groups in the number who discontinued (P 5 .146).”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductown data§ Statistical analysesNormality was tested with the Shapiro-Wilk test, and if rejected, data were rank-transformed before analysis.
“Normality assumptions were investigated with the Shapiro-Wilk test on the residuals.If the normality assumption was rejected (P , .01),data for that variable were ranked before the final analysis.”
Quote in the paperNot a substantial claimMay combine two claims.
Interpretationown data§ DiscussionThe 4 g/d OM3-FFA triglyceride results in the overall sample and in subjects with baseline triglycerides above 885 mg/dL were close to predictions from a regression of 16 published trials of 4 g/d OM3 products.
“are close to the line of best fit determined from an unweighted regression analysis of the relationship between mean or median baseline TGs and TG response to 4 g/d of pharmaceutical OM3 products”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [10][11][12]
Not checked in the free run.
- Rests on an assumption: Olive oil 4 g/d is an inert control that does not itself meaningfully alter triglycerides or non-HDL-C, so differences from olive oil can be attributed to OM3-FFA.
- Rests on an assumption: Subjects adhered to the TLC diet and maintained weight during the trial, so observed lipid changes are not due to diet or weight changes.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Study design and conductown data§ Study designThe study was conducted according to Good Clinical Practice, the Declaration of Helsinki, and US regulations; the protocol and consent were approved by ethics committees; and informed consent was obtained.
“This study was conducted according to Good Clinical Practice Guidelines, the Declaration of Helsinki (2000), and the United States 21 Code of Federal Regulations.The study protocol and informed consent documents were approved by the local responsible institutional review boards/independent ethics committees in North America, Europe, and India before the study was initiated.A signed informed cons”
Quote in the paperNot a substantial claimMay combine two claims.
Premisecitation§ DiscussionOmega-3 fatty acid treatment lowers triglycerides by reducing hepatic triglyceride secretion and enhancing triglyceride clearance from circulation.
“OM3 fatty acid treatment lowers the TG level by both reducing the amount of hepatic TG secretion and by enhancing the rate of TG clearance from circulation.”
Quote in the paperSubstantial claim0 of 1 sources checked- cites 17,[40][41][42][43][44][45][46]
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.
Premisecitation§ DiscussionLp-PLA2 participates in inflammation and is an independent predictor of cardiovascular disease risk.
“Lp-PLA 2 , an enzyme that participates in inflammation and that has been shown to be an independent predictor of cardiovascular disease risk, 6,[52][53][54]”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites 6,[52][53][54]
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Study design and conductown data§ Laboratory and safety assessmentsInvestigators were blinded to triglyceride results unless values exceeded 2000 mg/dL.
“Investigators were blinded to the TG results, unless the values were .2000mg/dL.”
Quote in the paperNot a substantial claimProbably not a substantial claim: may not pass S3 (load-bearing).
Interpretationnone given§ DiscussionThe smaller triglyceride reduction in the 3 g/d group than in the 2 or 4 g/d groups could be explained by random variation.
“It is notable that the degree of TG reduction was smaller in the 3-g/d group than in the 2-or 4-g/d treatment groups.However, random variation cannot be excluded as an explanation for this unexpected pattern”
Quote in the paperNot a substantial claim- Rests on an assumption: Olive oil 4 g/d is an inert control that does not itself meaningfully alter triglycerides or non-HDL-C, so differences from olive oil can be attributed to OM3-FFA.
- Rests on an assumption: Subjects adhered to the TLC diet and maintained weight during the trial, so observed lipid changes are not due to diet or weight changes.
Probably not a substantial claim: may not pass S3 (load-bearing).
Interpretationreasoning§ DiscussionThe placebo-corrected hs-CRP decrease seen with EPA ethyl ester may be explained by a non-neutral mineral oil control, because the differences arose from rises in control groups rather than falls from baseline with EPA ethyl ester.
“a potential explanation for that effect could be a non-neutral effect of the mineral oil control on hs-CRP levels, because the significant differences in hs-CRP responses were attributable to increases in the control groups of these trials and not to reductions from baseline with EPA-EE.”
Quote in the paperNot a substantial claimMay combine two claims.
Premisecitation§ DiscussionIn earlier omega-3 free fatty acid studies, gastrointestinal disturbance was common, prompting development of a coated capsule that prevents free fatty acid release in the stomach.
“In past studies with OM3-FFA, the incidence of gastrointestinal disturbance was high, which led to the development of a capsule with a coating to prevent the release of the free fatty acids into the stomach.”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [3] Davidson, 2012, A novel omega-3 free fatty acid formulation has dramatically improved bioavailability during a low-fat diet compared with omega-3-acid ethyl esters: The ECLIPSE (Epanova® compared to Lovaza® in a pharmacokinetic single-dose evaluation) study, J Clin Lipidol source
Not checked in the free run.
May combine two claims.
Premisecitation§ DiscussionArachidonic acid is associated with greater platelet aggregation and with production of prostaglandins and leukotrienes that increase platelet activation and vasoconstriction.
“which is linked to increased platelet aggregation and production of prostaglandins and leukotrienes that enhance platelet activation and vasoconstriction.59”
Quote in the paperSubstantial claim0 of 1 sources checked- cites [59] DeCaterina, 1990, Vascular prostacyclins is increased in patients ingesting omega-3 polyunsaturated fatty acids before coronary artery bypass graft surgery, Circulation source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ DiscussionInvestigators have described ethnicity as a possible source of inconsistent findings in studies of omega-3 fatty acid intake and cardiovascular outcomes.
“Ethnicity has been described as a factor that may contribute to inconsistencies in results from studies of the effects of OM3 fatty acid consumption on cardiovascular disease outcomes.60”
Quote in the paperNot a substantial claim0 of 1 sources checked- cites [60] Patel, 2010, Omega-3 polyunsaturated acids and cardiovascular disease: notable ethnic differences of unfulfilled promise?, J Thromb Haemost source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ DiscussionEarlier studies of omega-3 ethyl esters found lower lipoprotein-associated phospholipase A2.
“Previous studies with OM3-EEs have also shown reduced Lp-PLA 2 ,”
Quote in the paperNot a substantial claim0 of 2 sources checked- cites [34] Davidson, 2009, Effects of prescription omega-3-acid ethyl esters on lipoprotein particle concentrations, apolipoproteins AI and CIII, and lipoprotein-associated phospholipase A2 mass in statin-treated subjects with hypertriglyceridemia, J Clin Lipidol source
Not checked in the free run.
- cites [35] Maki, 2011, Effects of prescription omega-3-acid ethyl esters, coadministered with atorvastatin, on circulating levels of lipoprotein particles, apolipoprotein CIII and lipoprotein-associated phospholipase A2 mass in men and women with mixed dyslipidemia, J Clin Lipidol source
Not checked in the free run.
Probably not a substantial claim: may not pass S3 (load-bearing).
Premisecitation§ DiscussionRecent EPA ethyl ester studies reported a placebo-corrected decrease in high-sensitivity C-reactive protein.
“Although recent investigations of EPA-EE have reported a placebo-corrected reduction on hs-CRP, 23,26,55”
Quote in the paperNot a substantial claim0 of 3 sources checked- cites [23] Ballantyne, 2012, Efficacy and safety of eicosapentaenoic acid ethyl ester (AMR101) therapy in statin-treated patients with persistent high triglycerides (from the ANCHOR study), Am J Cardiol source
Not checked in the free run.
- cites [26] Bays, 2011, Eicosapentaenoic acid ethyl ester (AMR101) therapy in patients with very high triglyceride levels (from the Multi-center, plAcebo-controlled, Randomized, double-blInd, 12-week study with an open-label Extension [MARINE] trial), Am J Cardiol source
Not checked in the free run.
- cites [55] Bays, 2013, Icosapent ethyl, a pure ethyl ester of eicosapentaenoic acid: effects on circulating markers of inflammation from the MARINE and ANCHOR studies, Am J Cardiovasc Drugs source
Not checked in the free run.
The paper relies on this without support.
Olive oil 4 g/d is an inert control that does not itself meaningfully alter triglycerides or non-HDL-C, so differences from olive oil can be attributed to OM3-FFA.
“control (olive oil [OO] 4 g/d)”
“compared with 24.3% with OO”
The paper relies on this without support.
Subjects adhered to the TLC diet and maintained weight during the trial, so observed lipid changes are not due to diet or weight changes.
“Subjects were instructed to follow the National Cholesterol Education Program Therapeutic Lifestyle Changes (TLC) diet”
“be willing to maintain their customary activity level, follow the TLC diet with weight maintenance”
The paper relies on this without support.
The olive oil control does not itself alter the lipid or inflammatory endpoints, so differences from olive oil can be attributed to omega-3 free fatty acids.
“hs-CRP was not reduced with OM3-FFA compared with OO.”
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Initial trials of omega-3 CA demonstrated dose-dependent lowering of plasma triglyceride levels up to 31%.
“Initial trials of omega-3 CAdemonstrateddose-dependentloweringofplasmatriglyceride levels up to 31%. 14,15”
From Effect of High-Dose Omega-3 Fatty Acids vs Corn Oil on Major Adverse Cardiovascular Events in Patients at High Cardiovascular Risk (2020) · cites this paper as [14]
The Discussion (page unavailable) reports triglyceride reductions of 25.9%, 25.5%, and 30.9% at 2, 3, and 4 g/day, supporting the approximately 31% maximum. It also notes that the 3-g/day reduction was smaller than the 2-g/day reduction and that the study was not powered to define a dose-response curve, so a dose-dependent effect was not demonstrated. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThis is the first dose-response meta-analysis of the relationship between omega-3 PUFA intake and non-HDL-C changes.
“To our best knowledge, this is the first dose–response meta‐analysis of the relationship between ω3 PUFA intake and non‐HDL‐C changes, an indicator of the cholesterol content of all atherogenic lipoproteins. 100 , 150 , 151”
From Association Between Omega-3 Fatty Acid Intake and Dyslipidemia: A Continuous Dose-Response Meta-Analysis of Randomized Controlled Trials (2023) · cites this paper as [151]
Treatment with OM3FAs decreases plasma apoCIII levels.
“Treatment with OM3FAs decreases plasma apoCIII levels [7, 44].”
The Helsinki Heart Study reported a significant reduction in cardiovascular disease outcomes with gemfibrozil.
“Although the HHS reported a significant reduction in CVD outcomes with gemfibrozil, neither the FIELD nor the ACCORD studies involving fenofibrate showed a reduction in total CVD outcomes.”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [310]
The effect of fibrates was most evident in people with elevated triglycerides and low HDL cholesterol.
“The effect was most evident in people with elevated TG/low HDL-C levels.”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [310]
The LEADER trial in men with lower-extremity arterial disease failed to show that bezafibrate produced a clinically important reduction in combined cardiovascular disease endpoints.
“The LEADER trial included male participants with lower-extremity arterial disease and failed to show that bezafibrate could lead to a clinically important reduction in CVD combined endpoints.”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [310]
Neither the FIELD nor the ACCORD studies with fenofibrate showed a reduction in total cardiovascular disease outcomes.
“Although the HHS reported a significant reduction in CVD outcomes with gemfibrozil, neither the FIELD nor the ACCORD studies involving fenofibrate showed a reduction in total CVD outcomes.”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [310]
Decreases in nonfatal myocardial infarction rates with fibrates were reported, often from post hoc analyses.
“Decreases in the rates of nonfatal MI were reported, although often as a result of post hoc analyses.”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [310]
Only the ACCORD study has analyzed the effect of a fibrate as an add-on treatment to a statin.
“Only one study, ACCORD, has analysed the effect of a fibrate as an add-on treatment to a statin.”
From 2019 ESC/EAS guidelines for the management of dyslipidaemias: lipid modification to reduce cardiovascular risk (2019) · cites this paper as [310]
In patients with severe hypertriglyceridemia (≥500 mg/dl), omega-3 PUFA carboxylic acids (Epanova) at 2 or 4 g once daily reduced triglycerides by 30.9%, total cholesterol by 7.5%, and increased HDL-C by 5.8% and LDL-C by 19.4% from baseline.
“| Omega-3 PUFA carboxylic | Adjunct to diet to reduce triglyceride levels in patients | 0.2 | 0.55 | 2 g once daily or | -30.9 | -7.5 þ5.8 þ19.4 | |”
From Cardiovascular Impact of Nutritional Supplementation With Omega-3 Fatty Acids (2021) · cites this paper as [94]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
Each contradiction between two passages listed here was confirmed by an independent check.
Gastrointestinal withdrawals use the wrong denominator
MinorThe discussion says gastrointestinal events accounted for 3% of discontinuations. Earlier, the paper reports three gastrointestinal withdrawals in each active-treatment group-3% of subjects in each group-while total AE-related discontinuations were 5% to 7% of subjects per group. Gastrointestinal events therefore accounted for substantially more than 3% of discontinuations.
“(3% of discontinuations in the OM3-FFA groups were because of gastrointestinal AEs).”
“Discontinuation due to AEs, primarily gastrointestinal, ranged from 5% to 7% across dosage groups vs 0% for the OO group.Nine subjects withdrew because of gastrointestinal events among the OM3-FFA groups, and they were evenly distributed across the dosage groups: 3 (3%) in OM3-FFA 2 g/d, 3 (3%) in OM3-FFA 3 g/d, and 3 (3%) in OM3-FFA 4 g/d.”
Cites
Grundy, S. M., Bilheimer, D. W., Chait, A., Clark, L. T., Denke, M. A., Havel, R. J., Hazzard, W. R., Hulley, S. B., Hunninghake, D. B., Kreisberg, R. A., et al. (1993) · JAMA · doi:10.1001/jama.269.23.3015 · Cited by 27,944 · see citing works
Detection, evaluation, and treatment of high blood cholesterol in adults (Adult Treatment Panel III)
Grundy, S. M., Becker, D. M., Clark, L. T., Cooper, R., Denke, M. A., Howard, J. L., Hunninghake, D. B., Illingworth, D. R., Luepker, R. V., McBride, P. E., et al. (2002) · Civil War Book Review · Cited by 12,198 · see citing works
European Guidelines on cardiovascular disease prevention in clinical practice (version 2012)
Authors/Task Force Members:, Perk, J., De Backer, G., Gohlke, H., Graham, I., Reiner, Ž., Verschuren, M., Albus, C., Benlian, P., Boysen, G., et al. (2012) · European Heart Journal · doi:10.1093/eurheartj/ehs092 · Cited by 8,490 · see citing works
European guidelines on cardiovascular disease prevention in clinical practice: executive summary
Graham, I., Atar, D., Borch‐Johnsen, K., Boysen, G., Burell, G. K., Cífková, R., Dallongeville, J., Backer, G. D., Ebrahim, S. B. J., Gjelsvik, B., et al. (2007) · European Heart Journal · doi:10.1093/eurheartj/ehm316 · Cited by 3,840 · see citing works
Triglycerides and Cardiovascular Disease: A Scientific Statement From the American Heart Association
Miller, M., Stone, N. J., Ballantyne, C., Bittner, V., Criqui, M. H., Ginsberg, H. N., Goldberg, A. C., Howard, W. J., Jacobson, M. S., Kris-Etherton, P. M., et al. (2011) · Circulation · doi:10.1161/cir.0b013e3182160726 · Cited by 1,871 · see citing works
Graham (2007) · doi:10.1097/01.hjr.0000277983.23934.c9 · Cited by 1,647 · see citing works
n-3 fatty acids and serum lipoproteins: human studies
Harris, W. (1997) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/65.5.1645s · Cited by 1,243 · see citing works
STRUCTURE, FUNCTION, AND DIETARY REGULATION OF Δ6, Δ5, AND Δ9 DESATURASES
Nakamura, M., & Nara, T. (2004) · Annual Review of Nutrition · doi:10.1146/annurev.nutr.24.121803.063211 · Cited by 1,074 · see citing works
Boekholdt, S. M., Arsenault, B. J., Mora, S., Pedersen, T. R., LaRosa, J. C., Nestel, P. J., Simes, R. J., Durrington, P., Hitman, G. A., Welch, K. M. A., et al. (2012) · JAMA · doi:10.1001/jama.2012.366 · Cited by 795 · see citing works
Self-citationPollin, T. I., Damcott, C. M., Shen, H., Ott, S. H., Shelton, J., Horenstein, R. B., Post, W., McLenithan, J. C., Bielak, L. F., Peyser, P. A., et al. (2008) · Science · doi:10.1126/science.1161524 · Cited by 688 · see citing works
Unique Lipoprotein Phenotype and Genotype Associated With Exceptional Longevity
Barzilai, N. (2003) · JAMA · doi:10.1001/jama.290.15.2030 · Cited by 576 · see citing works
Omega-3 fatty acids and coronary heart disease risk: clinical and mechanistic perspectives
Harris, W. S., Miller, M., Tighe, A. P., Davidson, M. H., & Schaefer, E. J. (2008) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2007.11.008 · Cited by 552 · see citing works
Self-citationLipid-Related Markers and Cardiovascular Disease Prediction
The Emerging Risk Factors Collaboration (2012) · JAMA · doi:10.1001/jama.2012.6571 · Cited by 539 · see citing works
Sacks, F. M., Alaupovic, P., Moye, L. A., Cole, T. G., Sussex, B., Stampfer, M. J., Pfeffer, M. A., & Braunwald, E. (2000) · Circulation · doi:10.1161/01.cir.102.16.1886 · Cited by 490 · see citing works
Fatty Acid Regulation of Hepatic Gene Transcription
Jump, D. Β., Botolin, D., Wang, Y., Xu, J., Christian, B., & Demeure, O. (2005) · Journal of Nutrition · doi:10.1093/jn/135.11.2503 · Cited by 477 · see citing works
Why do omega-3 fatty acids lower serum triglycerides?
Harris, W. S., & Bulchandani, D. (2006) · Current Opinion in Lipidology · doi:10.1097/01.mol.0000236363.63840.16 · Cited by 398 · see citing works
Authors/Task Force Members:, Perk, J., Backer, G. D., Gohlke, H., Graham, I. D., Reiner, Ž., Verschuren, W. M. M., Albus, C., Benlian, P., Boysen, G., et al. (2012) · European Heart Journal · doi:10.1093/eurheartj/ehs254 · Cited by 390 · see citing works
Davidson, M. H., Stein, E. A., Bays, H. E., Maki, K. C., Doyle, R. T., Shalwitz, R. A., Ballantyne, C. M., & Ginsberg, H. N. (2007) · Clinical Therapeutics · doi:10.1016/j.clinthera.2007.07.018 · Cited by 385 · see citing works
Self-citationMechanisms for the Hypotriglyceridemic Effect of Marine Omega-3 Fatty Acids
Davidson, M. H. (2006) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2005.12.024 · Cited by 375 · see citing works
Self-citationRobinson, J. G., Wang, S., Smith, B. J., & Jacobson, T. A. (2009) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2008.10.024 · Cited by 368 · see citing works
Yahagi, N., Shimano, H., Hasty, A. H., Amemiya-Kudo, M., Okazaki, H., Tamura, Y., Iizuka, Y., Shionoiri, F., Ohashi, K., Osuga, J.-I., et al. (1999) · Journal of Biological Chemistry · doi:10.1074/jbc.274.50.35840 · Cited by 364 · see citing works
Human absorption of fish oil fatty acids as triacylglycerols, free acids, or ethyl esters
Lawson, L. D., & Hughes, B. G. (1988) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(88)80718-6 · Cited by 359 · see citing works
Bays, H. E., Ballantyne, C. M., Kastelein, J. J., Isaacsohn, J. L., Braeckman, R. A., & Soni, P. N. (2011) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2011.04.015 · Cited by 358 · see citing works
Self-citationOmega-3 fatty acid supplementation accelerates chylomicron triglyceride clearance
Park, Y., & Harris, W. S. (2003) · Journal of Lipid Research · doi:10.1194/jlr.m200282-jlr200 · Cited by 348 · see citing works
Ballantyne, C. M., Bays, H. E., Kastelein, J. J., Stein, E., Isaacsohn, J. L., Braeckman, R. A., & Soni, P. N. (2012) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2012.05.031 · Cited by 342 · see citing works
Self-citationSafety and Efficacy of Omacor in Severe Hypertriglyceridemia
Harris, W. S., Ginsberg, H. N., Arunakul, N., Shachter, N. S., Windsor, S. L., Adams, M., Berglund, L., & Osmundsen, K. (1997) · European Journal of Cardiovascular Prevention & Rehabilitation · doi:10.1177/174182679700400511 · Cited by 306 · see citing works
Davidson, M. H., Ballantyne, C. M., Jacobson, T. A., Bittner, V. A., Braun, L. T., Brown, A. S., Brown, W. V., Cromwell, W. C., Goldberg, R. B., McKenney, J. M., et al. (2011) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2011.07.005 · Cited by 262 · see citing works
Self-citationSafety and efficacy of Omacor in severe hypertriglyceridemia
Harris, W. S., Ginsberg, H. N., Arunakul, N., Shachter, N. S., Windsor, S. L., Adams, M., Berglund, L., & Osmundsen, K. (1997) · Journal of Cardiovascular Risk · doi:10.1097/00043798-199710000-00011 · Cited by 252 · see citing works
Abe, Y., El-Masri, B., Kimball, K. T., Pownall, H. J., Reilly, C., Osmundsen, K., Smith, C. W., & Ballantyne, C. M. (1998) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.18.5.723 · Cited by 214 · see citing works
Davidson, M. H., Johnson, J., Rooney, M. W., Kyle, M. L., & Kling, D. F. (2012) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2012.01.002 · Cited by 191 · see citing works
Self-citationChan, D. C., Watts, G. F., Mori, T. A., Barrett, P. H. R., Redgrave, T. G., & Beilin, L. J. (2003) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/77.2.300 · Cited by 185 · see citing works
Pownall, H. J., Brauchi, D., Kilinç, C., Osmundsen, K., Pao, Q., Payton-Ross, C., Gotto, A. M., & Ballantyne, C. M. (1999) · Atherosclerosis · doi:10.1016/s0021-9150(98)00301-3 · Cited by 179 · see citing works
Chan, D. C., Watts, G. F., Barrett, P. H. R., Beilin, L. J., Redgrave, T. G., & Mori, T. A. (2002) · Diabetes · doi:10.2337/diabetes.51.8.2377 · Cited by 160 · see citing works
Khan, S., Minihane, A.-M., Talmud, P. J., Wright, J. W., Murphy, M. C., Williams, C. M., & Griffin, B. A. (2002) · Journal of Lipid Research · doi:10.1016/s0022-2275(20)30473-9 · Cited by 145 · see citing works
Lawson, L. D., & Hughes, B. G. (1988) · Biochemical and Biophysical Research Communications · doi:10.1016/s0006-291x(88)80937-9 · Cited by 141 · see citing works
Bays, H. E., Ballantyne, C. M., Braeckman, R. A., Stirtan, W. G., & Soni, P. N. (2013) · American Journal of Cardiovascular Drugs · doi:10.1007/s40256-012-0002-3 · Cited by 141 · see citing works
Tan, C., Forster, L. F., CASLAKE, M. J., Bedford, D. K., Watson, T. D. G., McConnell, M., Packard, C. J., & Shepherd, J. (1995) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/01.atv.15.11.1839 · Cited by 137 · see citing works
Influence of n-3 fatty acid supplementation on the endogenous activities of plasma lipases
Harris, W., Lu, G., Rambjør, G., Wõlen, A., Ontko, J., Cheng, Q., & Windsor, S. (1997) · The American Journal of Clinical Nutrition · doi:10.1093/ajcn/66.2.254 · Cited by 135 · see citing works
DeCaterina, R., Giannessi, D., Mazzone, A., Bernini, W., Lazzerini, G., Maffei, S., Cerri, M., Salvatore, L., & Weksler, B. (1990) · Circulation · doi:10.1161/01.cir.82.2.428 · Cited by 134 · see citing works
Nordøy, Bønaa, Nilsen, Berge, Hansen, & Ingebretsen (1998) · Journal of Internal Medicine · doi:10.1046/j.1365-2796.1998.00297.x · Cited by 103 · see citing works
Stalenhoef, A. F. H., Graaf, J. D., Wittekoek, M. E., Bredie, S. J. H., Demacker, P. N. M., & Kastelein, J. J. P. (2000) · Atherosclerosis · doi:10.1016/s0021-9150(00)00381-6 · Cited by 101 · see citing works
Self-citationApolipoprotein CIII links dyslipidemia with atherosclerosis
Kawakami, A., & Yoshida, M. (2009) · Journal of Atherosclerosis and Thrombosis · doi:10.5551/jat.e607 · Cited by 98 · see citing works
Prescription omega-3 fatty acids for the treatment of hypertriglyceridemia
McKenney, J. M., & Sica, D. A. (2007) · American Journal of Health-System Pharmacy · doi:10.2146/ajhp060164 · Cited by 94 · see citing works
Offman, E., Marenco, T., Ferber, S., Johnson, J., Kling, D., Curcio, D., & Davidson, M. (2013) · Vascular Health and Risk Management · doi:10.2147/vhrm.s50464 · Cited by 92 · see citing works
Self-citationAnderson, J. L. (2008) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2008.04.015 · Cited by 90 · see citing works
Maki, K. C., Bays, H. E., Dicklin, M. R., Johnson, S. L., & Shabbout, M. (2011) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2011.09.001 · Cited by 81 · see citing works
Self-citationMaki, K. C., McKenney, J. M., Reeves, M. S., Lubin, B. C., & Dicklin, M. R. (2008) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2008.03.078 · Cited by 81 · see citing works
Self-citationWestphal, S., Orth, M., Ambrosch, A., Osmundsen, K., & Luley, C. H. (2000) · American Journal of Clinical Nutrition · doi:10.1093/ajcn/71.4.914 · Cited by 79 · see citing works
Ridker, P. M., MacFadyen, J. G., Wolfert, R. L., & Köenig, W. (2012) · Clinical Chemistry · doi:10.1373/clinchem.2011.180281 · Cited by 79 · see citing works
Musa-Veloso, K., Binns, M. A., Kocenas, A. C., Poon, T., Elliot, J. A., Rice, H., Oppedal-Olsen, H., Lloyd, H., & Lemke, S. (2010) · Nutrition Reviews · doi:10.1111/j.1753-4887.2010.00272.x · Cited by 73 · see citing works
Davidson, M. H., Maki, K. C., Bays, H., Carter, R., & Ballantyne, C. M. (2009) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2009.08.001 · Cited by 71 · see citing works
Self-citationBays, H. E., McKenney, J., Maki, K. C., Doyle, R. T., Carter, R. N., & Stein, E. (2010) · Mayo Clinic Proceedings · doi:10.4065/mcp.2009.0397 · Cited by 54 · see citing works
Self-citationOlivieri, O., Martinelli, N., Sandri, M., Bassi, A., Guarini, P., Trabetti, E., Pizzolo, F., Girelli, D., Friso, S., Pignatti, P. F., et al. (2005) · Clinical Chemistry · doi:10.1373/clinchem.2004.040477 · Cited by 50 · see citing works
Signori, C., DuBrock, C., Richie, J. P., Prokopczyk, B., Demers, L. M., Hamilton, C., Hartman, T. J., Liao, J., El‐Bayoumy, K., & Manni, A. (2012) · European Journal of Clinical Nutrition · doi:10.1038/ejcn.2012.60 · Cited by 49 · see citing works
Tatsuno, I., Saito, Y., Kudou, K., & Ootake, J. (2013) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2013.01.006 · Cited by 42 · see citing works
Raatz, S. K., Young, L. R., Picklo, M. J., Sauter, E. R., Qin, W., & Kurzer, M. S. (2012) · Nutrition Research · doi:10.1016/j.nutres.2011.12.006 · Cited by 35 · see citing works
PATEL, J. V., TRACEY, I., HUGHES, E. A., & LIP, G. Y. (2010) · Journal of Thrombosis and Haemostasis · doi:10.1111/j.1538-7836.2010.03956.x · Cited by 32 · see citing works
Maki, K. C., Lawless, A. L., Kelley, K., Dicklin, M. R., Kaden, V. N., Schild, A. L., Rains, T. M., & Marshall, J. W. (2011) · Journal of Cardiovascular Pharmacology · doi:10.1097/fjc.0b013e318210fca5 · Cited by 31 · see citing works
Self-citationSondermeijer, B. M., Rana, J. S., Arsenault, B. J., Shah, P. K., Kastelein, J. J. P., Wareham, N. J., Boekholdt, S. M., & Khaw, K. (2013) · European Journal of Clinical Investigation · doi:10.1111/eci.12129 · Cited by 30 · see citing works
Self-citationToth, P. P., McCullough, P. A., Wegner, M. S., & Colley, K. J. (2010) · Expert Review of Cardiovascular Therapy · doi:10.1586/erc.10.18 · Cited by 29 · see citing works
Phenotypes of hypertriglyceridemia caused by excess very-low-density lipoprotein
Sniderman, A. D., Tremblay, A., Graaf, J. D., & Couture, P. (2012) · Journal of clinical lipidology · doi:10.1016/j.jacl.2012.04.081 · Cited by 23 · see citing works
Maki, K. C., Lawless, A. L., Kelley, K., Dicklin, M. R., Schild, A. L., & Rains, T. M. (2011) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2011.06.005 · Cited by 21 · see citing works
Self-citationIn vivo studies of VLDL metabolism and LDL heterogeneity.
Demant, T., & Packard, C. J. (1998) · PubMed · Cited by 21 · see citing works
Saito, E., Okada, T., Iwata, F., & Kitamura, Y. (2012) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2012.03.005 · Cited by 2 · see citing works
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Mach, F., Baigent, C., Catapano, A. L., Koskinas, K. C., Casula, M., Badimon, L., Chapman, M. J., De Backer, G. G., Delgado, V., Ference, B. A., et al. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehz455 · Cited by 8,961 · see citing works
Mach, F., Baigent, C., Catapano, A. L., Koskinas, K. C., Casula, M., Badimon, L., Chapman, M. J., De Backer, G. G., Delgado, V., Ference, B. A., et al. (2019) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2019.08.014 · Cited by 4,854 · see citing works
2016 ESC/EAS Guidelines for the Management of Dyslipidaemias
Catapano, A. L., Graham, I., De Backer, G., Wiklund, O., Chapman, M. J., Drexel, H., Hoes, A. W., Jennings, C. S., Landmesser, U., Pedersen, T. R., et al. (2016) · European Heart Journal · doi:10.1093/eurheartj/ehw272 · Cited by 3,162 · see citing works
2016 ESC/EAS Guidelines for the Management of Dyslipidaemias
Catapano, A. L., Graham, I., De Backer, G., Wiklund, O., Chapman, M. J., Drexel, H., Hoes, A. W., Jennings, C. S., Landmesser, U., Pedersen, T. R., et al. (2016) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2016.08.018 · Cited by 1,582 · see citing works
Nicholls, S. J., Lincoff, A. M., Garcia, M., Bash, D., Ballantyne, C. M., Barter, P. J., Davidson, M. H., Kastelein, J. J. P., Koenig, W., McGuire, D. K., et al. (2020) · JAMA · doi:10.1001/jama.2020.22258 · Cited by 1,028 · see citing works
Self-citationNational Lipid Association Recommendations for Patient-Centered Management of Dyslipidemia: Part 2
Jacobson, T. A., Maki, K. C., Orringer, C. E., Jones, P. H., Kris-Etherton, P., Sikand, G., La Forge, R., Daniels, S. R., Wilson, D. P., Morris, P. B., et al. (2015) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2015.09.002 · Cited by 784 · see citing works
Self-citationSandesara, P. B., Virani, S. S., Fazio, S., & Shapiro, M. D. (2019) · Endocrine Reviews · doi:10.1210/er.2018-00184 · Cited by 626 · see citing works
Skulas-Ray, A. C., Wilson, P. W. F., Harris, W. S., Brinton, E. A., Kris-Etherton, P. M., Richter, C. K., Jacobson, T. A., Engler, M. B., Miller, M., Robinson, J. G., et al. (2019) · Circulation · doi:10.1161/cir.0000000000000709 · Cited by 488 · see citing works
A Brief Review of Cardiovascular Diseases, Associated Risk Factors and Current Treatment Regimes
Flora, G. D., & Nayak, M. K. (2019) · Current Pharmaceutical Design · doi:10.2174/1381612825666190925163827 · Cited by 488 · see citing works
Current knowledge of hypertriglyceridemic pancreatitis
Valdivielso, P., Ramírez-Bueno, A., & Ewald, N. (2014) · European Journal of Internal Medicine · doi:10.1016/j.ejim.2014.08.008 · Cited by 439 · see citing works
Lipid management in patients with chronic kidney disease
Ferro, C. J., Mark, P. B., Kanbay, M., Sarafidis, P. A., Heine, G. H., Rossignol, P., Massy, Z. A., Mallamaci, F., Valdivielso, J. M., Małyszko, J., et al. (2018) · Nature Reviews Nephrology · doi:10.1038/s41581-018-0072-9 · Cited by 275 · see citing works
Genetics and causality of triglyceride-rich lipoproteins in atherosclerotic cardiovascular disease
Rosenson, R. S., Davidson, M. H., Hirsh, B. J., Kathiresan, S., & Gaudet, D. (2014) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2014.09.042 · Cited by 260 · see citing works
Self-citationPPAR Agonists and Metabolic Syndrome: An Established Role?
Botta, M., Audano, M., Sahebkar, A., Sirtori, C. R., Mitro, N., & Ruscica, M. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19041197 · Cited by 253 · see citing works
Coronary heart disease risk: Low-density lipoprotein and beyond
Shaya, G. E., Leucker, T. M., Jones, S. R., Martin, S. S., & Toth, P. P. (2021) · Trends in Cardiovascular Medicine · doi:10.1016/j.tcm.2021.04.002 · Cited by 243 · see citing works
Triglyceride-rich lipoproteins as a causal factor for cardiovascular disease
Toth, P. (2016) · Vascular Health and Risk Management · doi:10.2147/vhrm.s104369 · Cited by 237 · see citing works
Jepsen, A.-M. K., Langsted, A., Varbo, A., Bang, L. E., Kamstrup, P. R., & Nordestgaard, B. G. (2016) · Clinical Chemistry · doi:10.1373/clinchem.2015.253757 · Cited by 218 · see citing works
Self-citationUnmet Need for Adjunctive Dyslipidemia Therapy in Hypertriglyceridemia Management
Ganda, O. P., Bhatt, D. L., Mason, R. P., Miller, M., & Boden, W. E. (2018) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2018.04.061 · Cited by 195 · see citing works
The clinical relevance of omega-3 fatty acids in the management of hypertriglyceridemia
Backes, J., Anzalone, D., Hilleman, D., & Catini, J. (2016) · Lipids in Health and Disease · doi:10.1186/s12944-016-0286-4 · Cited by 195 · see citing works
Triglycerides and Triglyceride-Rich Lipoproteins in the Causal Pathway of Cardiovascular Disease
Budoff, M. J. (2016) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2016.04.004 · Cited by 186 · see citing works
Apolipoprotein C-III: from pathophysiology to pharmacology
Norata, G. D., Tsimikas, S., Pirillo, A., & Catapano, A. L. (2015) · Trends in Pharmacological Sciences · doi:10.1016/j.tips.2015.07.001 · Cited by 182 · see citing works
Nicholls, S. J., Lincoff, A. M., Bash, D., Ballantyne, C. M., Barter, P. J., Davidson, M. H., Kastelein, J. J. P., Koenig, W., McGuire, D. K., Mozaffarian, D., et al. (2018) · Clinical Cardiology · doi:10.1002/clc.23055 · Cited by 167 · see citing works
Self-citationRecent advances in pharmacotherapy for hypertriglyceridemia
Sahebkar, A., Chew, G. T., & Watts, G. F. (2014) · Progress in Lipid Research · doi:10.1016/j.plipres.2014.07.002 · Cited by 166 · see citing works
Oscarsson, J., & Hurt-Camejo, E. (2017) · Lipids in Health and Disease · doi:10.1186/s12944-017-0541-3 · Cited by 158 · see citing works
2017 Taiwan lipid guidelines for high risk patients
Li, Y., Ueng, K., Jeng, J., Charng, M., Lin, T., Chien, K., Wang, C., Chao, T., Liu, P., Su, C., et al. (2017) · Journal of the Formosan Medical Association · doi:10.1016/j.jfma.2016.11.013 · Cited by 165 · see citing works
Dama, A., Shpati, K., Daliu, P., Dümür, Ş., Gorica, E., & Santini, A. (2024) · Nutrients · doi:10.3390/nu16040507 · Cited by 122 · see citing works
Chang, C.-H., Tseng, P.-T., Chen, N.-Y., Lin, P.-C., Lin, P.-Y., Chang, J. P. C., Kuo, F.-Y., Lin, J., Wu, M.-C., & Su, K.-P. (2018) · Prostaglandins Leukotrienes and Essential Fatty Acids · doi:10.1016/j.plefa.2018.01.001 · Cited by 103 · see citing works
Yang, X., Lee, S.-R., Choi, Y.-S., Alexander, V. J., Digenio, A., Yang, Q., Miller, Y. I., Witztum, J. L., & Tsimikas, S. (2016) · Journal of Lipid Research · doi:10.1194/jlr.m066399 · Cited by 103 · see citing works
Hershman, D. L., Unger, J. M., Crew, K. D., Awad, D., Dakhil, S. R., Gralow, J. R., Greenlee, H., Lew, D. L., Minasian, L. M., Till, C., et al. (2015) · Journal of Clinical Oncology · doi:10.1200/jco.2014.59.5595 · Cited by 101 · see citing works
Lipids, blood pressure and kidney update 2014
Banach, M., Aronow, W. S., Șerban, M.-C., Sahabkar, A., Rysz, J., Voroneanu, L. E., & Covic, A. C. (2015) · Pharmacological Research · doi:10.1016/j.phrs.2015.03.009 · Cited by 92 · see citing works
Prescription omega-3 fatty acid products containing highly purified eicosapentaenoic acid (EPA)
Brinton, E. A., & Mason, R. P. (2017) · Lipids in Health and Disease · doi:10.1186/s12944-017-0415-8 · Cited by 83 · see citing works
Fialkow, J. (2016) · American Journal of Cardiovascular Drugs · doi:10.1007/s40256-016-0170-7 · Cited by 80 · see citing works
Potential benefits of eicosapentaenoic acid on atherosclerotic plaques
Nelson, J. R., Wani, O. R., May, H. T., & Budoff, M. J. (2017) · Vascular Pharmacology · doi:10.1016/j.vph.2017.02.004 · Cited by 81 · see citing works
Bae, J. H., Lim, H., & Lim, S. (2023) · Advances in Nutrition · doi:10.1016/j.advnut.2023.03.014 · Cited by 78 · see citing works
Wang, T., Zhang, X., Zhou, N., Shen, Y., Li, B., Chen, B. E., & Li, X. (2023) · Journal of the American Heart Association · doi:10.1161/jaha.123.029512 · Cited by 73 · see citing works
Overview of Prescription Omega-3 Fatty Acid Products for Hypertriglyceridemia
WEINTRAUB, H. S. (2014) · Postgraduate Medicine · doi:10.3810/pgm.2014.11.2828 · Cited by 74 · see citing works
Detopoulou, P., Demopoulos, C. A., & Antonopoulou, S. (2021) · Nutrients · doi:10.3390/nu13020462 · Cited by 74 · see citing works
Chang, J. P., Chang, S., Yang, H.-T., Chen, H.-T., Chien, Y.-C., Yang, B., Su, H., & Su, K. (2019) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2019.03.012 · Cited by 66 · see citing works
Ito, M. K. (2015) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2015.06.012 · Cited by 67 · see citing works
Ruscica, M., Penson, P. E., Ferri, N., Sirtori, C. R., Pirro, M., Mancini, G. B. J., Sattar, N. A., Toth, P. P., Sahebkar, A., Lavie, C. J., et al. (2021) · Progress in Cardiovascular Diseases · doi:10.1016/j.pcad.2021.06.010 · Cited by 64 · see citing works
Cardiovascular Impact of Nutritional Supplementation With Omega-3 Fatty Acids
Weinberg, R. L., Brook, R. D., Rubenfire, M., & Eagle, K. A. (2021) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2020.11.060 · Cited by 63 · see citing works
Lipoproteins in chronic kidney disease: from bench to bedside
Speer, T., Ridker, P. M., von Eckardstein, A., Schunk, S. J., & Fliser, D. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehaa1050 · Cited by 66 · see citing works
Lipid lowering therapy in cardiovascular disease: From myth to molecular reality
Mourikis, P., Zako, S., Dannenberg, L., Nia, A. M., Heinen, Y., Busch, L., Richter, H., Hohlfeld, T., Zeus, T., Kelm, M., et al. (2020) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2020.107592 · Cited by 60 · see citing works
Baumfeld, Y., Novack, L., Wiznitzer, A., Sheiner, E., Henkin, Y., Sherf, M., & Novack, V. (2015) · PLoS ONE · doi:10.1371/journal.pone.0139164 · Cited by 61 · see citing works
Alexopoulos, A., Qamar, A., Hutchins, K., Crowley, M. J., Batch, B. C., & Guyton, J. R. (2019) · Current Diabetes Reports · doi:10.1007/s11892-019-1136-3 · Cited by 60 · see citing works
Nutraceuticals and Bioactive Components from Fish for Dyslipidemia and Cardiovascular Risk Reduction
Chiesa, G., Busnelli, M., Manzini, S., & Parolini, C. (2016) · Marine Drugs · doi:10.3390/md14060113 · Cited by 59 · see citing works
Lipids, blood pressure and kidney update 2015
Banach, M., Aronow, W. S., Șerban, M.-C., Rysz, J., Voroneanu, L. E., & Covic, A. C. (2015) · Lipids in Health and Disease · doi:10.1186/s12944-015-0169-0 · Cited by 57 · see citing works
Remnant cholesterol and ischemic heart disease
Varbo, A., & Nordestgaard, B. G. (2014) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000093 · Cited by 56 · see citing works
Self-citationTriglycerides, Atherosclerosis, and Cardiovascular Outcome Studies: Focus on Omega-3 Fatty Acids
Handelsman, Y., & Shapiro, M. D. (2016) · Endocrine Practice · doi:10.4158/ep161445.ra · Cited by 53 · see citing works
Dunbar, R. L., Nicholls, S. J., Maki, K. C., Roth, E. M., Orloff, D. G., Curcio, D., Johnson, J., Kling, D., & Davidson, M. H. (2015) · Lipids in Health and Disease · doi:10.1186/s12944-015-0100-8 · Cited by 52 · see citing works
Self-citationBallantyne, C. M., Bays, H. E., Philip, S., Doyle, R. T., Braeckman, R. A., Stirtan, W. G., Soni, P. N., & Juliano, R. A. (2016) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2016.08.005 · Cited by 52 · see citing works
Enkhmaa, B., Surampudi, P. N., Anuurad, E., & Berglund, L. (2015) · Europe PMC (PubMed Central) · Cited by 50 · see citing works
Zwartjes, M. S. Z., Gerdes, V. E. A., & Nieuwdorp, M. (2021) · Metabolites · doi:10.3390/metabo11080531 · Cited by 50 · see citing works
Omega-3 Fatty Acids in Cardiovascular Disease and Diabetes: a Review of Recent Evidence
Bhat, S. Z., Sarkar, S., Zaffar, D., Dandona, P., & Kalyani, R. R. (2023) · Current Cardiology Reports · doi:10.1007/s11886-022-01831-0 · Cited by 50 · see citing works
A Comparative Overview of Prescription Omega-3 Fatty Acid Products.
Ito, M. K. (2015) · PubMed Central · Cited by 49 · see citing works
Darwesh, A. M., Sosnowski, D. K., Lee, T. Y., Keshavarz-Bahaghighat, H., & Seubert, J. M. (2019) · Chemico-Biological Interactions · doi:10.1016/j.cbi.2019.04.037 · Cited by 49 · see citing works
Sahebkar, A., Simental‐Mendía, L. E., Mikhailidis, D. P., Pirro, M., Banach, M., Sirtori, C. R., & Reiner, Ž. (2018) · Annals of Medicine · doi:10.1080/07853890.2018.1511919 · Cited by 47 · see citing works
Miller, M. J., Ballantyne, C. M., Bays, H. E., Granowitz, C. B., Doyle, R. T., Juliano, R. A., & Philip, S. (2019) · The American Journal of Cardiology · doi:10.1016/j.amjcard.2019.05.057 · Cited by 49 · see citing works
Ballantyne, C. M., Bays, H. E., Braeckman, R. A., Philip, S., Stirtan, W. G., Doyle, R. T., Soni, P. N., & Juliano, R. A. (2016) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2016.02.008 · Cited by 47 · see citing works
Lipoprotein Lipase: Is It a Magic Target for the Treatment of Hypertriglyceridemia
Moon, J. H., Kim, K., & Choi, S. H. (2022) · Endocrinology and Metabolism · doi:10.3803/enm.2022.402 · Cited by 49 · see citing works
Karalis, D. G. (2016) · Advances in Therapy · doi:10.1007/s12325-016-0462-y · Cited by 48 · see citing works
Novel therapeutics in hypertriglyceridemia
Gryn, S. E., & Hegele, R. A. (2015) · Current Opinion in Lipidology · doi:10.1097/mol.0000000000000231 · Cited by 44 · see citing works
Bays, H. E., Ballantyne, C. M., Doyle, R. T., Juliano, R. A., & Philip, S. (2016) · Prostaglandins & Other Lipid Mediators · doi:10.1016/j.prostaglandins.2016.07.007 · Cited by 43 · see citing works
Baumfeld, Y., Novack, L., Wiznitzer, A., Sheiner, E., Henkin, Y., Sherf, M., & Novack, V. (2015) · PLoS ONE · doi:10.1371/journal.pone.0142462 · Cited by 43 · see citing works
PROMETHEUS: an observational, cross-sectional, retrospective study of hypertriglyceridemia in Russia
IuA, K., & Владиславовна, Х. Ю. (2015) · Cardiovascular Diabetology · doi:10.1186/s12933-015-0268-2 · Cited by 42 · see citing works
2016 ESC/EAS Guidelines for the Management of Dyslipidaemias
Catapano, A. L., Graham, I. M., Backer, G. D., Wiklund, O., Chapman, M. J., Drexel, H., Hoes, A. W., Jennings, C. S., Landmesser, U., Pedersen, T. R., et al. (2016) · Kardiologia Polska · doi:10.5603/kp.2016.0157 · Cited by 41 · see citing works
Del-Rio-Navarro, B. E., Miranda‐Lora, A. L., Huang, F., Hall-Mondragon, M. S., & Leija-Martínez, J. J. (2019) · Journal of Pediatric Endocrinology and Metabolism · doi:10.1515/jpem-2018-0409 · Cited by 41 · see citing works
Severe hypertriglyceridemia: Existing and emerging therapies
Malick, W. A., Do, R., & Rosenson, R. S. (2023) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2023.108544 · Cited by 44 · see citing works
Peppone, L. J., Inglis, J. E., Mustian, K. M., Heckler, C. E., Padula, G. D. A., Mohile, S. G., Kamen, C. S., Culakova, E., Lin, P., Kerns, S. L., et al. (2019) · JNCI Cancer Spectrum · doi:10.1093/jncics/pkz005 · Cited by 40 · see citing works
Review of Cardiometabolic Effects of Prescription Omega-3 Fatty Acids
Burke, M. F., Burke, F. M., & Soffer, D. E. (2017) · Current Atherosclerosis Reports · doi:10.1007/s11883-017-0700-z · Cited by 39 · see citing works
Stroes, E. S. G., Susekov, A. V., de Bruin, T. W. A., Kvarnström, M., Yang, H., & Davidson, M. H. (2018) · Journal of Clinical Lipidology · doi:10.1016/j.jacl.2017.10.012 · Cited by 38 · see citing works
Self-citationOmega-3 fatty acids for cardiovascular event lowering
Kaur, G., Mason, R. P., Steg, P. G., & Bhatt, D. L. (2024) · European Journal of Preventive Cardiology · doi:10.1093/eurjpc/zwae003 · Cited by 40 · see citing works
Yuan, M., Zhang, Y., Hua, T., Liu, X.-L., Liu, T., Yuan, R., Li, G., Zhu, Y., & Zhang, X. (2020) · Clinical Nutrition · doi:10.1016/j.clnu.2020.05.034 · Cited by 35 · see citing works
Recommended Intake of Fish and Fish Oils Worldwide
Richter, C. K., Skulas‐Ray, A. C., & Kris‐Etherton, P. M. (2016) · Elsevier eBooks · doi:10.1016/b978-0-12-802844-5.00003-8 · Cited by 35 · see citing works
History and future of omega-3 fatty acids in cardiovascular disease
Sperling, L. S., & Nelson, J. R. (2016) · Current Medical Research and Opinion · doi:10.1185/03007995.2015.1120190 · Cited by 34 · see citing works
Gabani, M. H., Shapiro, M. D., & Toth, P. P. (2023) · European Cardiology Review · doi:10.15420/ecr.2023.16 · Cited by 38 · see citing works
Secondary hypertriglyceridemia in children and adolescents
Blackett, P. R., Wilson, D. P., & McNeal, C. J. (2015) · Journal of clinical lipidology · doi:10.1016/j.jacl.2015.04.006 · Cited by 35 · see citing works
Targeting ApoC-III to Reduce Coronary Disease Risk
Khetarpal, S. A., Qamar, A., Millar, J. S., & Rader, D. J. (2016) · Current Atherosclerosis Reports · doi:10.1007/s11883-016-0609-y · Cited by 34 · see citing works
Sepidarkish, M., Morvaridzadeh, M., Akbari‐Fakhrabadi, M., Almasi‐Hashiani, A., Rezaeinejad, M., & Heshmati, J. (2019) · Diabetes & Metabolic Syndrome Clinical Research & Reviews · doi:10.1016/j.dsx.2019.03.018 · Cited by 34 · see citing works
Recent advances in synthetic pharmacotherapies for dyslipidaemias
Sirtori, C. R., Yamashita, S., Greco, M. F., Corsini, A., Watts, G. F., & Ruscica, M. (2019) · European Journal of Preventive Cardiology · doi:10.1177/2047487319845314 · Cited by 34 · see citing works
Blair, H. A., & Dhillon, S. (2014) · American Journal of Cardiovascular Drugs · doi:10.1007/s40256-014-0090-3 · Cited by 34 · see citing works
Larsen, L. E., Stoekenbroek, R. M., Kastelein, J. J. P., & Holleboom, A. G. (2019) · Arteriosclerosis Thrombosis and Vascular Biology · doi:10.1161/atvbaha.118.312028 · Cited by 34 · see citing works
Self-citationBays, H. E., Hallén, J., Vige, R., Fraser, D. A., Zhou, R., Hustvedt, S. O., Orloff, D. G., & Kastelein, J. J. P. (2015) · Journal of clinical lipidology · doi:10.1016/j.jacl.2015.10.012 · Cited by 32 · see citing works
Self-citationIverson, C., Bacong, A., Liu, S., Baumgartner, S., Lundström, T., Oscarsson, J., & Miner, J. N. (2018) · Scientific Reports · doi:10.1038/s41598-018-19252-x · Cited by 32 · see citing works
Morton, A. M., Furtado, J. D., Lee, J., Amerine, W., Davidson, M. H., & Sacks, F. M. (2016) · Journal of clinical lipidology · doi:10.1016/j.jacl.2016.09.005 · Cited by 32 · see citing works
Self-citationLomitapide for the treatment of hypertriglyceridemia
Berberich, A. J., & Hegele, R. A. (2016) · Expert Opinion on Investigational Drugs · doi:10.1080/13543784.2016.1254187 · Cited by 29 · see citing works
López-Toledano, M. A., Thorsteinsson, T., Daak, A. A., Maki, K. C., Johns, C., Rabinowicz, A. L., & Sancilio, F. D. (2017) · Clinical Therapeutics · doi:10.1016/j.clinthera.2017.01.020 · Cited by 28 · see citing works
Self-citationRemnant cholesterol in atherosclerotic cardiovascular disease: A systematic review and meta-analysis
Delialis, D., Georgiopoulos, G. A., Aivalioti, E., Konstantaki, C., Oikonomou, E., Bampatsias, D., Mavraganis, G., Vardavas, C. I., Liberopoulos, E. N., Stellos, K., et al. (2023) · Hellenic Journal of Cardiology · doi:10.1016/j.hjc.2023.04.007 · Cited by 31 · see citing works
de Toro‐Martín, J., Guénard, F., Rudkowska, I., Lemieux, S., Couture, P., & Vohl, M. (2017) · Journal of clinical lipidology · doi:10.1016/j.jacl.2017.10.020 · Cited by 27 · see citing works
Prescription Omega-3 Fatty Acid Products and Dietary Supplements Are Not Interchangeable.
Hilleman, D. E., & Smer, A. M. (2016) · PubMed · Cited by 26 · see citing works
Chang, J. P., Chang, S., Chen, H., Chien, Y.-C., Yang, H., Huang, S., Tseng, P., Chang, C., Gałecki, P., & Su, K. (2023) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2023.06.008 · Cited by 26 · see citing works
López-Toledano, M. A., Thorsteinsson, T., Daak, A. A., Maki, K. C., Johns, C., Rabinowicz, A. L., & Sancilio, F. D. (2017) · Journal of clinical lipidology · doi:10.1016/j.jacl.2017.01.017 · Cited by 26 · see citing works
Self-citationJia, X., Gao, F., Pickett, J. K., Al Rifai, M., Birnbaum, Y., Nambi, V., Virani, S. S., & Ballantyne, C. M. (2021) · Cardiovascular Drugs and Therapy · doi:10.1007/s10557-021-07204-z · Cited by 27 · see citing works
Managing dyslipidemia in patients with Type 2 diabetes
Tomlinson, B., Patil, N. G., Fok, M., & Lam, C. W. K. (2021) · Expert Opinion on Pharmacotherapy · doi:10.1080/14656566.2021.1912734 · Cited by 25 · see citing works
Current Treatment of Dyslipidemia: Evolving Roles of Non-Statin and Newer Drugs
KONES, R. J., & Rumana, U. (2015) · Drugs · doi:10.1007/s40265-015-0429-3 · Cited by 24 · see citing works
Dyslipidemia Management in 2020: An Update on Diagnosis and Therapeutic Perspectives
Karantas, I. D., Okur, M. E., Okur, N. Ü., & Siafaka, P. I. (2020) · Endocrine Metabolic & Immune Disorders - Drug Targets · doi:10.2174/1871530320666200810144004 · Cited by 25 · see citing works
The Road to Approval: a Perspective on the Role of Icosapent Ethyl in Cardiovascular Risk Reduction
Wang, X., Verma, S., Mason, R. P., & Bhatt, D. L. (2020) · Current Diabetes Reports · doi:10.1007/s11892-020-01343-7 · Cited by 24 · see citing works
Hober, A., Edfors, F., Ryaboshapkina, M., Malmqvist, J., Rosengren, L., Percy, A. J., Lind, L., Forsström, B., Uhlén, M., Oscarsson, J., et al. (2019) · Molecular & Cellular Proteomics · doi:10.1074/mcp.ra119.001765 · Cited by 23 · see citing works
Bioavailability of long-chain n-3 fatty acids from enriched meals and from microencapsulated powder
Hinriksdóttir, H. H., Jónsdóttir, V. L., Sveinsdóttir, K., Martinsdóttir, E., & Ramel, A. (2014) · European Journal of Clinical Nutrition · doi:10.1038/ejcn.2014.250 · Cited by 24 · see citing works
Omega-3 free fatty acids inhibit tamoxifen-induced cell apoptosis
Wu, S.-F., Guo, Y., Wu, Y., Zhu, S., He, Z., & Chen, Y. Q. (2015) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2015.02.103 · Cited by 23 · see citing works
Alsayed, N., Almahmeed, W. A., Alnouri, F., Al-Waili, K., Sabbour, H. M., Sulaiman, K., Zubaid, M., Ray, K. K., & Al‐Rasadi, K. (2021) · Atherosclerosis · doi:10.1016/j.atherosclerosis.2021.11.022 · Cited by 23 · see citing works
- Authors
- Kastelein, J. J. P., Maki, K. C., Susekov, A., Ezhov, M., Nordestgaard, B. G., Machielse, B. N., Kling, D., & Davidson, M. H.
- Affiliations
- Amsterdam UMC Location University of Amsterdam (NL)
- BioFortis (United States) (US)
- Corresponding author
- Kastelein, John J.P.
- Venue
- Journal of Clinical Lipidology
- Publisher
- Elsevier BV
- Published
- 2014-01
- Volume
- 8
- Issue
- 1
- Pages
- 94-106
- ISSN
- 1876-4789 (ISSN-L)
- 1933-2874
- OpenAlex
- W2099767767
- Cited by
- 233
- References
- 67
- Citations by year
- 2026: 10 · 2025: 7 · 2024: 6 · 2023: 18 · 2022: 10 · 2021: 22 · 2020: 20 · 2019: 22 · 2018: 13 · 2017: 27 · 2016: 36 · 2015: 27 · 2014: 13 · 2013: 1
- FWCI
- 23.73
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of clinical lipidology (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Topics
- Health Sciences › Nursing › Nutrition and Dietetics › Fatty Acid Research and Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipid metabolism and disorders
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Keywords
- severe hypertriglyceridemia, eicosapentaenoic acid, docosahexaenoic acid, triglyceride lowering, olive oil, lipid-lowering efficacy, LDL cholesterol, non-HDL cholesterol, apolipoprotein C-III, lipoprotein-associated phospholipase A2, C-reactive protein
- MeSH terms
- Female, Humans, Male, Middle Aged, Triglycerides, Hypertriglyceridemia, Fatty Acids, Omega-3, Treatment Outcome, Endpoint Determination
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