Future Novel Treatment Strategies in CAD/PAD


Deepak L. Bhatt, MD, MPH: We’ve only got a few minutes left. Maybe for this last bit we can talk about what other therapies are out there, emerging, soon to be experimental. What are you really excited about, Vamsi?

Vamsi Krishna, MD: I think this idea of reducing inflammation. This word inflammation has been utilized since the 1980s, trying to target atherosclerosis as an inflammatory marker. There is a trial called CANTOS that was published in 2017, I believe. It was an anti—interleukin-1β agent, and it had I believe a 25% reduction in MACE [major adverse cardiac event] outcomes.

Deepak L. Bhatt, MD, MPH: Fifteen percent overall.

Vamsi Krishna, MD: OK, 15% overall.

Deepak L. Bhatt, MD, MPH: If you look in patents who had CRP [C-reactive protein] reductions, then the benefits were much larger.

Vamsi Krishna, MD: Right. If it actually reduced the CRP, there was benefit. I think the age of having monoclonal antibodies and going after interleukins and TNF [tumor necrosis factor] seems to be going back to your point of, the physiology isn’t as simple as when we learned it in medical school. If you block this, this outcome will happen. It’s much more complex. And now we’re getting targeting therapy, like PCSK9s [proprotein convertase subtilisin/kexin type 9]. We’re trying to eliminate or decrease our adverse effects but also targeting a multimodality approach. As an interventional and a vascular person, it’s exciting. It’s fun when we treat someone, but it’s really fun when we treat them and we never have to see them again back in the hospital for 10, 15 years. It’s very gratifying that we’ve really helped change their life. So I think the process right now to go after inflammation is very exciting.

And then the second thing I’m really excited about is also this machine-based learning and artificial intelligence [AI]. I’ve had the ability to see some of the infancy on this for what it can do to systems. I think when we’re dealing with chronic conditions and have residual risk, identifying that still is a major problem, and not everyone is equipped to do so, even though it should be as easy as it is. I think identifying those high-risk patients immediately in a health care system and automatically having a system approach to treat those patients can help really reduce the health care cost. Because right now cardiovascular disease is costing $555 billion, and they project it’s going to be $1.1 trillion in 2030. So there’s no way we can sustain this pace, and I think having these amazing therapies and being able to target it is going to be awesome.

Deepak L. Bhatt, MD, MPH: That’s a great couple of things. What do you think is hot next?

Manesh Patel, MD: I think the most interesting thing in cardiovascular medicine right now is, we are in the age of having not only personalization. I was a poo-pooher of the genetics of cardiovascular disease and the transcription into biology. But at the American Heart Association meetings and others, what we’re starting to see is a novel approach with molecules. So we’ve always thought, oh, there’s a protein, block the protein, and the protein blocks the receptor. That’s how stuff works. That works well. We give it to people, we say please really take it every day. But the idea is that you might inhibit the transcription of an RNA molecule into that protein and you could do a shot twice a year. Inclisiran is one of these agents that’s being studied for LDL [low-density lipoprotein] lowering, but there’s also epigenomic modifiers.

There are other targets now where we are going to get to the age and have the financial conversation about, what if I did say—instead of just coming in for a flu shot—I’m going to give you a shot, you’re going to come in twice a year, and I’m going to get your LDL down to 30 mg/dL and you’re not going to take a pill. How many people are going to line up at the CVS for that? That’s going to be a really transformative thing, that we’re going to really rely on our primary care physicians to help us take care of. I think we have to see those data, but if you said to me in 5 years what’s going to be really exciting, it’s that we’re going to know a lot more specific risks for our patients, and we’re going to be much more specific about our therapy.

Deepak L. Bhatt, MD, MPH: So inflammation, AI, a personalized medicine, genetics. They took all the easy stuff. What’s next? What do you think is exciting?

John Eikelboom, MBBS, MSc, FRCPC: I think what’s still incredibly exciting, no biases on my part, is optimizing antithrombotic therapy. And I’ve heard it said we’ve come to the end of the road and we’ve had so many therapies now, let’s move to other things. But I think nothing could be further from the truth. I think there are at least 3 ways we can optimize antithrombotic therapy. One is we’ve got to continue to seek the sweet spot with our dosing, and when I say dosing, that may be a combination of treatments, like COMPASS has shown us, hitting that sweet spot and suddenly we’ve got a benefit, where in the past warfarin plus aspirin produced no benefit.

I think the second method is targeting the right pathway. Regarding the story about the contact pathway, if we could target that selectively, not only might we prevent mechanical valve-related thrombosis, but by stopping this amplification pathway, we could also achieve greater efficacy with less bleeding risk. And then the third I think is the upstream targeting of drivers of thrombogenesis. And you’ve touched on 1, inflammation, incredibly exciting. But there are other things. There are nets. These are these complexes floating about the circulation with neutrophils and strands of genetic material and platelets. They are an intriguing story, these little monsters going around and firing up coagulation. And then recently we had a paper on CHIP, clonal hematopoiesis of indeterminate potential. How exciting is that? We have these little pieces of errant DNA causing trouble. Cardiovascular medicine is incredibly exciting, and there’s so much more that we’re going to achieve in the years to come.

Deepak L. Bhatt, MD, MPH: Well, those were really 3 great answers. Hopefully, this session has been useful to the audience in terms of what you can do practically but also a little bit of a glimpse into the future. Those were really wonderful futuristic types of answers. Thank you all for your contributions to this discussion. You’ve been a great faculty. On behalf of our panel, we thank you at home for joining us, and we hope you found this Peer Exchange discussion to be useful and informative. Thank you very much.

Transcript edited for clarity.

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