Deepak Bhatt, MD: Subgroup Analyses of REDUCE-IT Trial

Few treatments have captivated physicians across multiple specialties the way icosapent ethyl (Vascepa) and the REDUCE-IT trials have grabbed the attention of cardiologists and endocrinologists in recent years.

Beginning at the American Heart Association 2018 meeting in Chicago and continuing through the American Diabetes Association 2019 meeting in San Francisco, data from the trial and subsequent analyses have been a talking point since the trial was completed. Most recently, subgroup analyses have been performed to determine the impact of treatment with icosapent ethyl on certain subgroups within the 8000-person study population.

Multiple different subanalyses have enabled physicians to develop a greater understanding of icosapent ethyl’s impact on patients. Recent analyses have examined rates of limb ischemia, reduction of total and secondary cardiovascular events, and the impact of treatment in patients with lower baseline triglyceride levels.

To breakdown the findings and impact of these recent analyses, MD Magazine® sat down with lead REDUCE-IT investigator Deepak Bhatt, MD, MPH, executive director of Interventional Cardiovascular Programs at Brigham and Women's Hospital and professor of medicine at Harvard Medical School. A full transcript of that conversation can be found below.

MD Mag: What were the outcomes of the REDUCE-IT trial and what were the results of the recent subgroup analyses?

Bhatt: The primary endpoint of the REDUCE-IT trial was so-called 5-point MACE—or major adverse cardiovascular events—meaning cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or revascularization. This was significantly reduced in the overall trial—about a 25% relative risk reduction—that was highly statistically significant. As well, the key secondary endpoint of cardiovascular death, MI, stroke—so-called 'hard MACE,' was also significantly reduced by about 26%.

We've done additional analyses of the data looking not just a time to first event—the conventional way of doing such analyses, but instead also looking at total events—that is, the sum of initial events and recurrent events—and have found a 30% reduction in total events, which from a patient's perspective, of course that's how they look at things. Patients care about having second events.

That is, they'd rather not have a stroke after MI or a cardiovascular death after an episode of unstable angina. So, from a patient-centered perspective, perhaps the total events is really the more appropriate way of looking at data—though the conventional historic way is time to first event, but really any way you slice the data significant reductions, both in relative and absolute terms, in important ischemic events.

We've also examined a number of different subgroups. Most recently, patients were examined by their baseline tertile of triglyceride levels, and what we found—not that the trial was designed or powered for subgroup analyses such trials never are—but we did find significant reductions in ischemic events in all 3 tertiles, including the lowest tertile of baseline triglycerides. And that included patients with triglycerides as low as a 100, even though the inclusion criteria as stated was really 150, but we allowed variation and triglycerides.

And indeed, there was even greater variation when we looked at an average of a couple of measurements—as is known to be the case of triglyceride. So, bottom line is we got patients with triglycerides as low as a 100, but even those in that range of 100-150 or so seemed to derive substantial benefit from icosapent ethyl versus placebo arguing—at least indirectly—that some of the benefit might be beyond just triglyceride reduction.