Effects of Icosapent Ethyl on Total Ischemic Events

Bhatt, Deepak L.; Steg, Ph. Gabriel; Miller, Michael; Brinton, Eliot A.; Jacobson, Terry A.; Ketchum, Steven; Doyle, Ralph T.; Juliano, Rebecca A.; Jiao, Lixia; Granowitz, Craig; Tardif, Jean‐Claude; Gregson, John; Pocock, Stuart J.; Ballantyne, Christie M.; Investigators, Reduce-It

doi:10.1016/j.jacc.2019.02.032

Cited by 217 publications

(153 citation statements)

References 54 publications

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“…After a follow-up period of 4.9 years, icosapent ethyl was found to have a statistical benefit on reducing ischemic events in subjects with hypertriglyceridemia. 56 Was the apparent success of the REDUCE-IT trial due to increased dosing of the omega-3 polyunsaturated fatty acid derivative, study design or other factors? This question is difficult to answer because neither trial analyzed circulation levels of omega-3 polyunsaturated fatty acid or their metabolites before and after treatment.…”

Section: Discussionmentioning

confidence: 99%

<p>Progressive Loss of Corneal Nerve Fibers and Sensitivity in Rats Modeling Obesity and Type 2 Diabetes Is Reversible with Omega-3 Fatty Acid Intervention: Supporting Cornea Analyses as a Marker for Peripheral Neuropathy and Treatment</p>

Coppey¹,

Davidson²,

Shevalye³

et al. 2020

DMSO

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Purpose: To determine whether cornea nerve fiber density and/or corneal function are valid markers for early detection and treatment of peripheral neuropathy in rats modeling prediabetes and type 2 diabetes. Methods: High-fat feeding combined without or with low-dose streptozotocin was used to create rat models for prediabetes and type 2 diabetes that were longitudinally studied for loss of structure and function of sensory nerves in the cornea and skin as well as nerve conduction velocity and vascular reactivity of epineurial arterioles. There were three time points examined in each of the three conditions with 12 rats per group. The latest time point (24 weeks of high-fat diet with or without 16 weeks of hyperglycemia) was used to examine reversibility of neuro and vascular pathology following 16 weeks of treatment with menhaden oil, a natural source of long-chain omega-3 polyunsaturated fatty acids. The number of rats in the intervention study ranged from 6 to 17. Results: Our longitudinal study demonstrated that vascular and neural dysfunction associated with obesity or type 2 diabetes occur early and are progressive. Decrease in cornea nerve fiber length and function were valid markers of disease in both the pre-diabetic and diabetic rat models and were more sensitive than decrease in intraepidermal nerve fiber density of the skin and thermal nociception of the hindpaw. Late intervention with menhaden oil significantly reversed both vascular and peripheral nerve damage induced by chronic obesity or type 2 diabetes. Conclusion: These studies provide support for examination of corneal structure and function as an early marker of peripheral neuropathy in prediabetes and type 2 diabetes. Furthermore, we demonstrate that omega-3 polyunsaturated fatty acids derived from fish oil are an effective treatment for peripheral neuropathy that occurs with chronic obesity or type 2 diabetes.

show abstract

Section: Discussionmentioning

confidence: 99%

<p>Progressive Loss of Corneal Nerve Fibers and Sensitivity in Rats Modeling Obesity and Type 2 Diabetes Is Reversible with Omega-3 Fatty Acid Intervention: Supporting Cornea Analyses as a Marker for Peripheral Neuropathy and Treatment</p>

Coppey¹,

Davidson²,

Shevalye³

et al. 2020

DMSO

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show abstract

“…Lipolysis of TG-rich lipoproteins may release oxidized free-fatty acids (FFA) and lysolecithin, further stimulating endothelial cell inflammation and coagulation [38]. A post-hoc evaluation of the REDUCE-IT study [39] reports a significant reduction of CV events in patients with hypertriglyceridemia treated with high dose EPA, and indicates that even low levels of plasma TG, e.g. between 81 and 131 mg/dL can carry a CV risk [39].…”

Section: Lipid Mediated-inflammationmentioning

confidence: 99%

“…A post-hoc evaluation of the REDUCE-IT study [39] reports a significant reduction of CV events in patients with hypertriglyceridemia treated with high dose EPA, and indicates that even low levels of plasma TG, e.g. between 81 and 131 mg/dL can carry a CV risk [39].…”

Section: Lipid Mediated-inflammationmentioning

confidence: 99%

PCSK9 inhibition and inflammation: A narrative review

et al. 2019

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“…Specifically, first events fall by 25%, the second ones by 32%, the third ones by 31% and the fourth ones or more by 48%. 67 Interestingly, a secondary analysis based on baseline triglyceride tertiles showed that icosapent ethyl reduced ischaemic events regardless of triglyceride basal levels, that is, À21% (triglyceride levels !81 to 190 mg/dl), À20% (>190 to 250 mg/dL) and À32% (>250 to <1401 mg/dL). 68 Concerning safety, the rate of atrial fibrillation was higher in the icosapent ethyl group versus placebo (5.3% vs. 3.9%), as was the percentage of peripheral oedema (6.5% vs. 5.0%).…”

mentioning

confidence: 99%

Recent advances in synthetic pharmacotherapies for dyslipidaemias

Sirtori

Yamashita

Greco

et al. 2019

Eur J Prev Cardiolog

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Despite the demonstrated benefits of statins and injectable biologics, there is a need for new and safe oral agents for addressing classical lipid targets, low-density lipoprotein cholesterol (LDL-C), triglycerides and high-density lipoprotein cholesterol (HDL-C). LDL-C is unquestionably causal in the development of atherogenesis and atherosclerotic cardiovascular disease, but new options are required to address triglyceride-rich lipoproteins and lipoprotein(a). For hypercholesterolaemia, pitavastatin provides a very low dose and potent statin that does not adversely affect glucose metabolism; bempedoic acid acts at a biochemical step preceding hydroxymethylglutaryl-CoA reductase and is not associated with muscular side effects. For hypertriglyceridaemia, pemafibrate displays a unique and selective agonist activity on peroxisomal proliferator activated receptor-α that does not elevate homocysteine or creatinine. Although omega-3 fatty acids supplementation is not effective in secondary prevention, high dose eicosapentaenoic ethyl ester can lead to a remarkable fall in first and recurrent events in high risk patients with hypertriglyceridaemia/low HDL-C. Gemcabene, a dicarboxylic acid regulating apolipoprotein B-100, is effective in reducing both cholesterol and triglycerides. Among cholesteryl ester transfer protein antagonists that elevate HDL-C, only anacetrapib reduces cardiovascular events. Probucol stimulates reverse cholesteryl ester transport, lowers LDL-C stabilizing plaques and may lower incidence of cardiovascular events. These agents, which act through novel mechanisms, afford good and potentially safe treatment choices that may increase adherence and the attainment of therapeutic targets.

show abstract

Effects of Icosapent Ethyl on Total Ischemic Events

Cited by 217 publications

References 54 publications

<p>Progressive Loss of Corneal Nerve Fibers and Sensitivity in Rats Modeling Obesity and Type 2 Diabetes Is Reversible with Omega-3 Fatty Acid Intervention: Supporting Cornea Analyses as a Marker for Peripheral Neuropathy and Treatment</p>

<p>Progressive Loss of Corneal Nerve Fibers and Sensitivity in Rats Modeling Obesity and Type 2 Diabetes Is Reversible with Omega-3 Fatty Acid Intervention: Supporting Cornea Analyses as a Marker for Peripheral Neuropathy and Treatment</p>

PCSK9 inhibition and inflammation: A narrative review

Recent advances in synthetic pharmacotherapies for dyslipidaemias

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