The case for adding eicosapentaenoic acid (icosapent ethyl) to the ABCs of cardiovascular disease prevention.

The high-purity eicosapentaenoic acid (EPA) prescription fish oil-derived omega-3 fatty acid (omega-3), icosapent ethyl (IPE), was recently approved by the United States Food and Drug Administration (FDA) for cardiovascular disease (CVD) prevention in high-risk patients. This approval is based on the 25% CVD event risk reduction observed with IPE in the pre-specified primary composite endpoint (cardiovascular [CV] death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or hospitalization for unstable angina) in the landmark Reduction of Cardiovascular Events with Icosapent Ethyl-Intervention Trial (REDUCE-IT). Notably, this reduction in CVD event risk with IPE was an incremental benefit to well-controlled low-density lipoprotein cholesterol; patients in REDUCE-IT had elevated triglyceride (TG) levels (135-499 mg/dL) and either had a history of atherosclerotic CVD or diabetes with additional CV risk factors. Given the CVD event risk reduction in REDUCE-IT, within a year following trial results, several global medical societies added IPE to their clinical guidelines. IPE is a stable, highly purified, FDA-approved prescription EPA ethyl ester. In contrast, mixed omega-3 products (docosahexaenoic acid + EPA combinations) have limited or no evidence for CVD event risk reduction, and nonprescription fish oil dietary supplements are not regulated as medicine by the FDA. We offer our perspective and rationale for why this evidence-based EPA-only formulation, IPE, should be added to the 'E' in the ABCDEF methodology for CV prevention. We provide multiple lines of evidence regarding an unmet need for CVD prevention beyond statin therapy, IPE clinical trials, IPE cost-effectiveness analyses, and proposed pleiotropic (non-lipid) mechanisms of action of EPA, as well as other relevant clinical considerations. See Figure 1 for the graphical abstract.[Figure: see text].

Atrial fibrillation and mortality in African American patients with heart failure: results from the African American Heart Failure Trial (A-HeFT).

BACKGROUND: Atrial fibrillation (AF) is common in patients with heart failure (HF) and portends a worsened prognosis. Because of the low enrollment of African American subjects (AAs) in randomized HF trials, there are little data on AF in AAs with HF. This post hoc analysis reviews characteristics and outcomes of AA patients with AF in A-HeFT. METHODS AND RESULTS: A total of 1,050 AA patients with New York Heart Association class III/IV systolic HF, well treated with neurohormonal blockade (87% ß-blockers, 93% angiotensin-converting enzyme inhibitor and/or angiotensin receptor blocker), were randomized to an added fixed-dose combination of isosorbide dinitrate/hydralazine (FDC I/H) or placebo. Atrial fibrillation was confirmed in 174 (16.6%) patients at baseline and in an additional 9 patients who developed AF during the study, for a final cohort of 183 (17.4%). Comparison of patients with AF versus no AF revealed the following: mean age 61 ± 12 versus 56 ± 13 years (P < .001), systolic blood pressure (BP) 124 ± 18 versus 127 ± 18 mm Hg (P = .044), diastolic BP 74 ± 11 versus 77 ± 10 mm Hg (P = .002), creatinine level 1.4 ± 0.5 versus 1.2 ± 0.5 mg/dL (P < .001), and brain natriuretic peptide 431 ± 443 versus 283 ± 396 pg/mL (P < .001). No significant difference was observed in ejection fraction, left ventricular end-diastolic diameter, or quality-of-life scores. However, AF increased the risk of mortality significantly among AA patients (P = .018), and the use of FDC I/H reduced the risk of mortality in patients with AF (HR 0.21, P = .002). CONCLUSION: African Americans with HF and AF (vs no AF) were older, had lower BP, and had higher creatinine and brain natriuretic peptide levels. Mortality and morbidity were worse when AF was present, and these data suggest that there may be an enhanced survival benefit with the use of FDC I/H in AA patients with HF and AF.