PracticeUpdate Cardiology Best of 2018

CONFERENCE COVERAGE 25

American Heart Association Scientific Sessions 2018 10–12 NOVEMBER 2018 • CHICAGO, ILLINOIS, USA By the PracticeUpdate Editorial Team

© AHA/Scott Morgan 2018

Prescription Omega-3 Fatty Acids Reduce Risk of Major Adverse Cardiac Events Benefits were seen for both primary or secondary cardiovascular disease prevention. P atients given a proprietary fish oil omega-3 fatty acid blend (icosapent ethyl) are at reduced risk for major adverse cardiac events, according to the results of the REDUCE-IT trial. Deepak Bhatt, MD, of Harvard Medical School in Boston suggested that icosap- ent ethyl may have metabolic effects and other mechanisms of actions distinct from modulation of triglyceride levels.

“REDUCE-IT supports the position that icosapent ethyl is safe, well tolerated, and reduces the likelihood of cardiovascular events in stable, high-risk hypertriglycer- idemic patients taking evidence-based statin therapy,” said discussant Carl E. Orringer, MD, of the University of Miami, during a press conference, calling it a “very important, seminal trial.” Dr. Orringer suggested caution in broadly interpreting the results, however, noting that a “limitation of the study is that 90% of the patients were identified as white; thus, the potential benefits of icosapent ethyl in patients of other ethnicities remains unclear.” Patients included in the REDUCE-IT trial were either age ≥45 years with established cardiovascular disease (secondary preven- tion cohort) or age ≥50 years with one or more additional risk factors for cardiovas- cular disease (primary prevention cohort). All included patients were on stable statin therapy with or without ezetimibe for ≥4 weeks prior to inclusion. Of 19,212 patients screened, 8179 were randomized 1:1 to receive either icosap- ent ethyl (2 g twice daily) or placebo. The median trial follow-up duration was 4.9 years. In future work, Dr. Bhatt hopes to analyze the cost effectiveness of icosapent ethyl therapy; he predicts that this therapy will indeed be found to be cost effective, as the number needed to treat, 21, is quite low. The REDUCE-IT trial was sponsored by Amarin Pharma. www.practiceupdate.com/c/76134

The REDUCE-IT trial met its primary end- point objective, with icosapent ethyl significantly reducing risk of major adverse cardiac events (a composite measure that included cardiovascular death, non-fa- tal myocardial infarction, non-fatal stroke, coronary revascularization, and unstable angina) relative to placebo (HR 0.75; CI 0.68−0.83, P < .001). REDUCE-IT also met a key secondary end- point objective that consisted of harder cardiovascular outcome measures (car- diovascular death, non-fatal myocardial infarction, and non-fatal stroke), with icos- apent ethyl offering a significant advantage relative to placebo (11.2% vs 14.8%, HR 0.74; CI 0.65−0.83, P < .001). One striking result: Cardiovascular death alone was reduced by as much as 20% for patients taking icosapent ethyl rather than placebo (4.3% vs 5.2%, P = .03). Surprisingly, trial participants received ben- efit from icosapent ethyl regardless of their baseline triglyceride levels or triglyceride levels achieved at one year. During a presentation given to the press at AHA 2018, study principal investigator

Subgroups of patients who experienced particularly favorable outcomes during the REDUCE-IT trial included those with ele- vated baseline triglycerides, those who were <65 years old, those who were in secondary prevention, those who were not already taking ezetimibe, as well as those who were already on higher-intensity sta- tin therapy. Although the safety profile of isocapent ethyl was generally favorable, patients receiving icosapent ethyl were significantly more likely to be hospitalized for atrial fibril- lation or flutter than were patients receiving placebo (3.1% vs 2.1%, P = .004). There was also a clinically meaningful signal towards increased bleeding events for patients receiving icosapent ethyl rather than pla- cebo (2.7% vs 2.1%, P = .06). A result that could not easily be explained was the observation that LDL choles- terol levels were significantly elevated in the placebo group. Dr. Bhatt noted that it was unclear if this effect was due to the treatment or an artifact of the placebo, also noting that it would not explain the observed 25% relative risk reduction.

VOL. 3 • NO. 4 • 2018