Icosapent ethyl is a highly purified ethyl ester of the omega-3 fatty acid, eicosapentaenoic acid, derived from fish oil. It is indicated to reduce the risk of cardiovascular events in statin-treated adults at high cardiovascular risk with elevated triglycerides (≥1.7mmol/l) and established cardiovascular disease, or diabetes and at least one other cardiovascular risk factor.
The mechanism by which icosapent ethyl reduces cardiovascular risk is not completely understood. It is thought to be multifactorial, involving improved lipoprotein profile, anti-inflammatory and antioxidant effects, reduced macrophage accumulation, improved endothelial function, increased fibrous cap thickness/stability, and antiplatelet effects. Reduction of triglyceride levels appears to provide only a minor contribution.
The randomised, double-blind REDUCE-IT trial, involving patients with established cardiovascular disease or with diabetes and other risk factors, showed that those who were treated with icosapent ethyl had a significantly lower risk of ischaemic events than those who received placebo.
Participants, who were taking statins and had a fasting triglyceride level of 1.52–5.63mmol/l and an LDL-cholesterol level of 1.06–2.59mmol/l, were randomly assigned to receive 2g icosapent ethyl twice daily or placebo.
The primary endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularisation, or unstable angina. The key secondary endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, or nonfatal stroke.
A total of 8179 patients were enrolled (70.7% for secondary prevention of cardiovascular events) and were followed for a median of 4.9 years. A primary endpoint event occurred in 17.2% of patients in the icosapent ethyl group, compared with 22.0% of patients in the placebo group (hazard ratio 0.75; 95% CI 0.68–0.83; p<0.001); the corresponding rates of the key secondary endpoint were 11.2% and 14.8% (hazard ratio 0.74; 95% CI, 0.65–0.83; p<0.001).
A larger percentage of patients in the icosapent ethyl group than in the placebo group were hospitalised for atrial fibrillation or flutter (3.1% vs 2.1%, p=0.004). Serious bleeding events occurred in 2.7% of the patients in the icosapent ethyl group and 2.1% of those in the placebo group (p=0.06).
Patients taking icosapent ethyl should be monitored for clinical evidence of atrial fibrillation or atrial flutter, particularly if they have a history of these conditions. Patients taking concomitant antithrombotic agents, ie, antiplatelet agents and/or anticoagulants, may be at increased risk of bleeding and should be monitored periodically.