Icosapent Ethyl Linked to Reduced Risk of Cardiovascular Events

Use of icosapent ethyl (Vascepa), a highly purified eicosapentaenoic acid (EPA), may be associated with a reduction in risk of adverse cardiovascular events in Japanese patients with chronic coronary artery disease (CAD) who were also being treated with statins, according to results from the RESPECT-EPA trial presented at the American Heart Association annual meeting.

In this video, Deepak Bhatt, MD, MPH, the director of Mount Sinai Heart at the Icahn School of Medicine at Mount Sinai and the Mount Sinai Health System in New York City, discusses the study.

Following is a transcript of his remarks:

This was a study done in Japan, randomization to 1.8 g a day of icosapent ethyl versus not. That's what open label means, that there wasn't a matching placebo, but it was randomized. These were patients, again from Japan, who had known cardiovascular disease, but actually who ended up having essentially normal triglycerides, unlike say, REDUCE-IT, where everyone had high triglycerides. And these were patients with, I'd say, reasonably well controlled LDL average -- LDL baseline was like 80 mg/dL or something like that.

So these patients were randomized, it was a bit of an underpowered study outta the gate, about 1,200 or so patients in each arm. So, perhaps a bit optimistic in terms of powering in this trial as well. But the overall primary endpoint was a composite of cardiovascular death, nonfatal MI, nonfatal ischemic stroke, unstable angina, coronary revascularization.

And I'll say the primary endpoint was met, but, you know, one could quibble about the statistics. The P value was 0.054, the upper bound of the 95% confidence interval was 1.001, I think. So, one could say, strictly speaking, that's not a statistically significant value because it's not 0.05 or less. But again, I thought pretty close for that primary endpoint -- a hazard ratio of 0.785.

The secondary endpoint, which was sudden cardiac death, MI, unstable angina, coronary revascularization, there, the hazard ratio was 0.73. There, the P value was 0.03. So that was clearly statistically significant. Looking at the Kaplan-Meier curves for both the primary endpoint and the secondary endpoint, it was clear that a few years after randomization, the curves were clearly separating.

So, my assessment was that it was a positive trial, that there's something there that, in this population, this dose worked.

I'll just point out, compared with REDUCE-IT, this was a lower dose of icosapent ethyl, 1.8 g a day, REDUCE-IT used 4 g total per day. As well, these are Japanese patients and their EPA levels are higher than in Western populations. They did do some sort of enrichment here based on EPA:AA ratio, but even still their levels are like an order of magnitude higher than in Western populations. And I think the lack of high triglycerides here, I mean, that's a powerful risk factor. One can debate whether it's a modifiable risk factor per se, but for sure if your trigs are elevated despite statin and dietary counseling, you're at higher risk. So, much lower risk population than REDUCE-IT.

But, qualitatively, in other, I'd say, positive trials, much like JELIS (Japan EPA Lipid Intervention Study), a prior Japanese trial, also open-label with some limitations, but there as well a hazard ratio that favored the study drug. Once more, that was a lower dose, 1.8. So, to me, you know, it's a consistency across multiple different trials. And, you know, I think there's something there to EPA-based therapy.

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