[99] The results from REDUCE-IT may not be generalizable to all patients represented in the spectrum of CV risk. Most of the study subjects were high-risk patients as evidenced by 70% of those enrolled having a history of CVD. Although patients without a history of atherosclerotic CVD were enrolled, primary prevention patients represented a minority of those studied. Further, a subgroup analysis of the primary prevention cohort did not find a difference in CV outcomes. Although beneficial effects in higher risk primary prevention populations might be demonstrated in contemporary studies not captured in this review or with future investigations, the Work Group determined the REDUCE-IT results alone are insufficient to suggest icosapent ethyl for CV risk reduction in patients without a history of CVD. The results from REDUCE-IT are applicable to many patients classified as high risk by virtue of a history of CVD. However, the inclusion criteria utilized limit its application to part of the secondary prevention population only. Subjects were restricted to those with elevated TG levels (median 216 mg/dL, 90% of patients >150 mg/dL), 90% of whom were on stable doses of moderate- to high-dose statins for at least four weeks before the intervention. As such, the reduction in CVD outcomes by 25% pertain to secondary prevention populations on statin therapy with hypertriglyceridemia. The composite outcome included coronary revascularization, which many deem as a less clinically valid outcome. For some, this might be a cause for concern that positive interpretations of the results are misleading and rendered by outcomes less important to patients. However, a statistically and clinically significant reduction was demonstrated in each of the component endpoints, including vascular death and other patient-important outcomes. 