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|Objective:||To evaluate the effectiveness of AMR101 as an add-on to statin treatment in reducing major cardiovascular (CV) events in high-risk patients|
|Study design:||Multicentre, randomized, double-blind placebo-controlled, parallel group study|
8,000 men and women (³45 years) with residual elevated triglycerides (>150 mg/dL or 1.7 mmol/L) despite statin therapy for at least 4 weeks, with or at high risk of CV disease. Concomitant treatment with niacin >200 mg/day or fibrates; any omega-3 fatty acid medications; dietary supplements containing omega-3 fatty acids (e.g., flaxseed oil, fish oil, krill oil, or algal oil); or bile acid sequestrants was prohibited.
There is a growing body of evidence linking elevated triglycerides and risk for CV disease.(1) Indeed, the position statement from the R3i highlights that high triglycerides are commonly associated with low high-density lipoprotein (HDL) cholesterol, atherogenic dyslipidemia, which itself is associated with increased CV risk.(2) For example, in the Action to Control Cardiovascular Risk in Diabetes (ACCORD) Lipid study, simvastatin-treated type 2 diabetes patients with atherogenic dyslipidemia (triglycerides ≥204 mg/dL and HDL cholesterol ≤34 mg/dL) at baseline had a 70% increased risk of CV events compared with those without this dyslipidemic profile, even with LDL-C at or near goal. (3)
There is evidence from the Japan EPA Lipid Intervention Study (JELIS) that targeting elevated triglycerides in high-risk statin-treated patients with omega-3 fatty acids significantly reduced major coronary events (Fig).4 However, the dose used in this trial was less than that recommended by guidelines.(5,6) Moreover, with the current prescription formulation, there is also a risk of increased low-density lipoprotein (LDL) cholesterol levels, which may be attributed to the docosahexaenoic acid component.(7)
Fig: In JELIS, Supplementation with omega-3 fatty acids (1.8 g/day EPA) significantly reduced major coronary events.(4)
AMR101 differs from the current prescription formulation of omega-3 fatty acids in that it solely contains the ethyl ester of EPA. In Phase II trials,(8) AMR101 (4 g/day) significantly reduced median triglycerides (by 21.5%) without any increase in LDL cholesterol levels. Moreover, the reduction in triglycerides was greater in patients receiving high-intensity statin regimens (median reductions 20.2% with atorvastatin 40-80 mg, rosuvastatin 20-40 mg or simvastatin 80 mg) versus less intensive regimens.
Together, these data provide a rationale for testing the hypothesis that targeting elevated triglycerides, a component of atherogenic dyslipidemia, may offer the potential to reduce the residual risk of CV events in high-risk patients treated with statin therapy. Results from REDUCE-IT are anticipated in 2017.
1. Nordestgaard BG, Benn M, Schnohr P, Tybjærg-Hansen A. Nonfasting triglycerides and risk of myocardial infarction, ischemic heart disease, and death in men and women. JAMA 2007;298:299–308.
|Key words||atherogenic dyslipidemia, omega-3 fatty acids, residual cardiovascular risk, triglycerides|