REDUCE-IT shows 30% drop in total MACE with icosapent ethyl

NEW ORLEANS — A daily dose of icosapent ethyl is associated with a reduction in first and repeat major adverse cardiovascular events (MACE) for patients who remain at high risk despite taking a statin, a new analysis found.

The study, presented at the American College of Cardiology’s scientific sessions, suggests the purified eicosapentaenoic acid (EPA) product may be more protective than previously reported. The primary analysis of the REDUCE-IT trial was released in November and showed the medication was linked to a 25 percent reduction in a first MACE event when compared to a placebo. But the reduction is actually 30 percent when considering both initial and repeat events, including cardiovascular death, myocardial infarction, stroke, coronary revascularization or hospitalization for unstable angina.

“If we only look at the first event, that’s a traditional, statistical way of doing things and a conservative and appropriate approach, but then from a patient’s perspective or from a healthcare economics perspective, we lose this big part of the pie,” said Deepak L. Bhatt, MD, MPH, a professor of medicine at Harvard, director of interventional cardiovascular programs at Brigham and Women’s Hospital Heart & Vascular Center and lead author of the study.

REDUCE-IT randomized 8,179 statin-treated patients to either 4 mg per day of icosapent ethyl or a placebo. The patients had a median LDL cholesterol of 75 mg/dL at baseline, median triglycerides of 216 mg/dL and an additional risk factor of atherosclerosis (71 percent) or diabetes (29 percent).

Over a median follow-up of 4.9 years, 1,606 primary MACE events occurred and 1,303 subsequent events occurred—meaning 44.8 percent of the outcomes wouldn’t have been captured if follow-up stopped with the first event.

As previously reported, first events were lowered by 25 percent in patients treated with icosapent ethyl. In addition, second events dropped by 32 percent, third events by 31 percent and fourth or more events by 48 percent.

Bhatt said for every 1,000 patients matching the characteristics of those included in the study, 159 total events could be prevented with five years of treatment. That includes 12 cardiovascular deaths, 42 heart attacks, 14 strokes, 76 coronary revascularizations and 16 hospitalizations for unstable angina.

“From my perspective, I think that’s important to patients,” Bhatt said. “They don’t just care about their first event; they care about the second event, especially if that one happens to be a fatal one but even otherwise. And from a third-party payer perspective, health economics perspective, a societal perspective, a public health perspective—potentially a very large impact we can have with this intervention.”

Eileen Handberg, PhD, a research professor of medicine at the University of Florida, said she appreciated the total-events approach and believes it should be replicated in future cardiovascular trials.

“I think the implication is that this kind of analysis should be done in all trials that have MACE outcomes, because … the primary is generally the first occurrence of something but people do stay in the trial and they do go on to have other events but this generally doesn’t get reported,” said Handberg, who wasn’t involved in the study. “So, I think this is kind of a paradigm shift for clinical trial reporting and I applaud the group in thinking about this.”

Bhatt and colleagues’ work was published online in the Journal of the American College of Cardiology at the time of the ACC.19 presentation. The study was supported by funding from Amarin, which developed icosapent ethyl and sells it under the brand name Vascepa.

The drug is currently FDA-approved for patients with triglycerides above 500 mg/dL, but the REDUCE-IT data will likely be a key piece of the company’s efforts to expand the treatment to a wider population.