Case-Based Evidence for Cardiovascular Risk Reduction - Episode 5
Deepak Bhatt, MD, MPH: Matt, we can just move to you while thinking about icosapent ethyl and the EVAPORATE trial, which was another trial using the same drug and same dose of icosapent ethyl. You presented it as a late-breaking clinical trial at the American Heart Association [AHA], the interim analysis, a prespecified interim analysis of that, just this past AHA. That was a study looking at progression of atherosclerosis on coronary CT [computed tomography] angiography. Do you want to review for the audience what that interim analysis found?
Matthew J. Budoff, MD, FACC, FAHA: Sure, it was a mechanistic study to parallel the REDUCE-IT trial. As you mentioned, it was looking at serial CT angiography. We did a study of CT angiography at baseline. We did a 9-month CT angiogram and then an 18-month CT angiogram. As you mentioned, we reported the interim analysis at American Heart Association as a late breaker, and that paper is now in press at cardiovascular research. It showed that with the administration of 4 g of icosapent ethyl, there was a 19% reduction in total noncalcified plaque and a 42% reduction in total plaque compared with placebo. It slowed the plaque progression. It did not achieve its primary stopping end point, which was a reduction in low-attenuation plaque that was significant enough to stop the trial. We’ve just completed the 18-month data, the final analysis, and I’ll be presenting that at the European Society of Cardiology Congress meeting in August 2020.
Deepak Bhatt, MD, MPH: That’s really exciting. Really terrific findings. I’ll interject with another study of the same drug, icosapent ethyl, which was a pilot study that just got started up in Toronto, Canada. It’s something that Subodh Verma and colleagues there are orchestrating. Basically, it’s a 100-patient pilot of individuals who tested COVID-19 [coronavirus disease 2019] positive and were randomized to either icosapent ethyl or no icosapent ethyl, and to assess the effect on inflammatory biomarkers, things like hsCRP [high-sensitivity C-reactive protein], at 2 weeks. It’s an assessment of icosapent ethyl on biomarkers earlier than it has ever been done, just at 2 weeks.
Furthermore, it is using a loading dose of icosapent ethyl. The usual dosage, which is a total of 4 g a day, or 2 g twice a day with meals, was how we studied it in REDUCE-IT. But what is being studied here is an 8 g total per day loading dose for 3 days and then the 4 g total per day thereafter for the remainder of those 2 weeks. I will hopefully provide some interesting information about COVID-19. But irrespective of the COVID-19 aspect of things, we want to see whether there are any early effects on inflammatory biomarkers. Also, even beyond that aspect, we want to see if a loading dose is tolerated. Potentially if a loading dose is tolerated in this situation, it might then be studied in other situations, such as acute MI [myocardial infarction], or acute stroke or at the time that we have perfusion or revascularization.
Hopefully this will open the door for lots of other studies. It’s just a pilot study, but nevertheless might open the door for future studies, not just in COVID-19 but for non–COVID-19 populations as well. I just mentioned that for the sake of interest.
Transcript Edited for Clarity