In patients on statin therapy with established cardiovascular disease (CVD) who also have elevated cholesterol and triglycerides, icosapent ethyl was associated with a 25% reduction in risk for cardiovascular events, according to the full results of the Reduction of Cardiovascular Events with Icosapent Ethyl–Intervention Trial (REDUCE-IT) presented at the American Heart Association 2018 Scientific Sessions in Chicago.
Researchers for the study, led by principal investigator Deepak L. Bhatt, MD, of Brigham and Women’s Hospital in Boston, evaluated whether high-dose icosapent ethyl lowered ischemic event rates in at-risk patients taking statins. The randomized, double-blind, placebo-controlled study included a total of 8,179 patients who were followed for a median of 4.9 years. Patients were randomized to either 2 grams icosapent ethyl twice daily (total daily dose of 4 grams) or placebo. The primary study endpoint was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina, with key secondary endpoints of composite cardiovascular death, nonfatal MI, infarction, or nonfatal stroke.
According to the study results, a primary endpoint event occurred in 17.2% of patients in the icosapent ethyl vs. 22.0% in the placebo group (HR=0.75; 95% CI, 0.68 to 0.83; P<0.001). The corresponding rates of the secondary endpoint were 11.2% and 14.8% (HR=0.74; 95% CI, 0.65 to 0.83; P<0.001), and the additional rates for the various ischemic endpoints were significantly lower as well in the icosapent ethyl group. A small but significant increase in atrial fibrillation/atrial flutter was observed (P=0.004), and a trend toward serious bleeding events was also reported in the icosapent ethyl group (P=0.06).
Dr. Bhatt noted in his presentation that the study limitations prevented it from commenting upon the mechanism of the benefit observed in the study (analyses of biomarkers and genetics are planned), nor on the cost-effectiveness, although a full cost-effectiveness analysis is also in the planning phases.
Discussant Carl E. Orringer, MD, associate professor at the University of Miami Miller School of Medicine, proposed several possible mechanisms of benefit seen with icosapent ethyl, including lipid/protein reductions, anti-thrombotic effects, anti-inflammatory effects, membrane stabilization, plaque stabilization and other possible effects exclusive to icosapent ethyl itself.
Read the full REDUCE-IT manuscript in the New England Journal of Medicine.