Dr Matthew Budoff on the Benefits of Cardiac CT Use

Advances in imaging have made assessment of atherosclerosis non-invasive, while the EVAPORATE trial demonstrates how cardiac CT can assist in looking at a host of different therapies, said Matthew Budoff, MD, professor of medicine at the David Geffen School of Medicine at UCLA and investigator at The Lundquist Institute.

Transcript:

The American Journal of Managed Care® (AJMC®):In EVAPORATE the only secondary endpoint which did not achieve a significant difference between control and intervention groups was dense calcium. What might account for this?

Dr. Budoff: Calcification is probably the last of the stages of atherosclerosis, so it's the least modifiable. So we saw low attenuation plaque, the vulnerable, or necrotic, core changed a lot, fibrofatty plaque, the softer plaque, changed moderately and fibrous plaque change less and then calcified plaque change the least. So I think that actually makes sense from a biological mechanism, that the most earliest plaques and the most vulnerable plaques changed the most, and the more stable plaques, like those with a lot of fibrous tissue or those with dense calcium, changed less. The P-value for calcification in multivariate analysis was .0531. So, you know, from a purist standpoint, it didn't change significantly. But some people would say .053 is pretty close to .05 and is close to statistical significance. But either way, I think it makes sense biologically that the more stable plaque changes less than the earlier softer plaques.

AJMC®: As reduction of triglycerides on its own is not producing the dramatic drop in CV events, what are your thoughts on expanding the scope of patients receiving icosapent ethyl (Vascepa)?

Dr. Budoff: While I agree that triglyceride lowering isn't the primary benefit, I think those with high triglycerides are still a potential target. We have a number of populations where the target population is based on an abnormality of something, but we don't always treat that specific thing. For many years, diabetes, for example, the presence of diabetes meant your high cardiovascular risk and the treatment wasn't control the Hemoglobin A1c, the treatment was add other therapies. I think we still should be using icosapent ethyl largely in patients who have elevated triglycerides because that's where the benefit was shown to be the greatest. We have data now from triglycerides of 135 and up, and this group is still high risk. I want to emphasize that patients with elevated triglycerides, maybe because of metabolic syndrome and diabetes, and other factors, patients with elevated triglycerides are high risk, and they appear to benefit from icosapent ethyl. Whether it works in patients with normal triglycerides, I think that does deserve further study. We could not address that in EVAPORATE, because we did the EVAPORATE trial the same as the REDUCE IT study, and both of them used entry criteria for triglycerides of 135 and up.

AJMC®: Do you have any final thoughts you would like to share?

Dr. Budoff: Well, I just wanted to point out that the use of cardiac CT now has become highly reproducible. The reduction in radiation dose does allow us to do these type of trials, where we can do serial studies and assess does drug A do better than drug B, or does drug A do better than placebo over time .We've had some early studies looking at statins with this serial CT angiography and we've published on the testosterone, that testosterone increases atherosclerosis plaque in our placebo controlled randomized trial. Now we've been able to show that icosapent ethyl reduces plaque. So I do think that it's a nice model. It's not invasive, it's easy, but I do think it's an important way to assess some of the benefits without having to do intravascular ultrasound, and take patients to the catheterization lab twice, with all of the associated risks.

I think the advances in imaging have made our assessment of atherosclerosis now non-invasive. And I think that's an important part of the message of EVAPORATE, that this is a potential tool to look at a host of different therapies that we now have. We're now doing a trial with GLP-1 receptor agonists with semaglutide to see if that slows plaque progression, because that's also shown outcome benefit without a clear mechanism of action.