National Lipid Association Scientific Statement on Icosapent Ethyl
- Orringer CE, Jacobson TA, Maki KC
- National Lipid Association Scientific Statement on the use of icosapent ethyl in statin-treated patients with elevated triglycerides and high or very-high ASCVD risk. J Clin Lipidol 2019 Nov 2:[Epub ahead of print].
The following are key points to remember about this statement from the National Lipid Association on use of icosapent ethyl (IPE):
- The National Lipid Association now makes a Class I recommendation for use of IPE (4 g/d) to reduce cardiovascular risk in patients
- ≥45 years of age with clinical atherosclerotic cardiovascular disease (ASCVD) or
- ≥50 years of age with diabetes mellitus requiring medication and ≥1 additional risk factor;
- already on high-intensity or maximally tolerated statin therapy;
- with fasting triglycerides 135-499 mg/dL; and
- with or without ezetimibe.
- Additional risk factors are defined as
- men ≥55 years of age or women ≥65 years of age;
- cigarette smoker or stopped within 3 months;
- treated or untreated hypertension;
- high-density lipoprotein cholesterol (HDL-C) ≤40 mg/dl in men or ≤50 mg/dl in women;
- high-sensitivity C-reactive protein (hs-CRP) >3.0 mg/dL;
- creatinine clearance <60 mL/min and >30 mL/min;
- microalbuminuria or macroalbuminuria; and
- ankle-brachial index <0.9 without symptoms of intermittent claudication.
- IPE now joins ezetimibe and PCSK9 inhibitors for use as an adjunct to statins for ASCVD risk reduction.
- REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial) Trial served as the main basis for review of IPE for ASCVD risk reduction by the National Lipid Association. REDUCE-IT results were published in the New England Journal of Medicine on January 3, 2019.
- REDUCE-IT was a randomized, double-blind, placebo-controlled trial of high-dose IPE in 8,179 select patients. Primary composite endpoint occurred in 17.2% of IPE-treated patients versus 22.0% of placebo-treated controls (hazard ratio 0.75; p < 0.001).
- The 39.9% median reduction in hs-CRP in REDUCE-IT suggests that an anti-inflammatory effect, in addition to changes in plasma lipids, may be a mechanism of benefit in cardiovascular risk reduction. Other potential mechanisms are also explored.
- The statement describes additional evidence supporting the new recommendation: observational studies, results from prior randomized controlled trials, JELIS (Japan EPA Lipid Intervention Study), epidemiologic and Mendelian randomization studies, and prior meta-analyses.
- The paper also discusses the central role of low-density lipoprotein cholesterol and non-HDL-C as a root cause of atherosclerosis and the identification of hypertriglyceridemia as a marker of increased residual ASCVD risk in statin-treated patients.
- The statement reviews endorsements regarding treatment with IPE from other professional organizations, including the American Diabetes Association, European Society of Cardiology, and European Atherosclerosis Society.
- Several ongoing trials (STRENGTH [Outcomes Study to Assess Statin Residual Risk Reduction With Epanova in High CV Risk Patients With Hypertriglyceridemia], EVAPORATE [Effect of Vascepa on Improving Coronary Atherosclerosis in People With High Triglycerides Taking Statin Therapy], OMEMI [Omega-3 Fatty Acids in Elderly Patients With Acute Myocardial Infarction], and PROMINENT [Pemafibrate to Reduce Cardiovascular Outcomes by Reducing Triglycerides in Patients With Diabetes]) may shed light on mechanisms of benefit from IPE and other therapies.
Keywords: Hypertriglyceridemia, Lipids, Cholesterol, HDL, Cholesterol, LDL, Eicosapentaenoic Acid, Dyslipidemias, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Primary Prevention, Triglycerides, Diabetes Mellitus
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