Unmet Needs and Emerging Approaches to Management of Polyvascular Disease

Deepak Bhatt, MD, MPH: Let’s move on to the final segment to see what our panel thinks are the latest and greatest things coming down the pike to treat high-risk patients and particularly patients with CAD [coronary artery disease] who are at high risk, patients with PAD [peripheral artery disease], patients with polyvascular disease. Manesh, I’ll start with you and work my way down the table. What are the big unmet needs, and what things—in terms of drugs, procedures, or lifestyle approaches—will target those unmet risks?

Manesh Patel, MD: That’s a great question. It’s something that we struggle with as we try to think about how we can eradicate atherosclerosis, especially as we think about the burden on our population and the health equity issues inherent that have been laid bare over the last several years with COVID-19 and other things. If I go back to my thinking about where we are with atherothrombosis, there are a few big opportunities. I said it was inflammatory atherothrombosis, so understanding that first part is important. There are strategies coming, but the biggest unmet need is on both the implementation side and the discovery side. On the implementation side, we have proved therapies that aren’t getting used.

The reason we’re having this conversation is we just talked about some therapies that might reduce mortality in cardiovascular disease. I’ll use the A-Fib [atrial fibrillation] example: 12 years ago, we presented the first DOAC [direct oral anticoagulant] data. This was the first year that more than 50% of people worldwide will get a DOAC. The amount of time it takes from something being proven to getting to our patients—I’ll call it the last mile—is probably where we should spend a lot of time.

What are the areas in the first mile? Concerning areas for discovery that are the biggest, we need to do screening studies. We’re at the point with CT scans and some other things that, instead of saying there’s an ASCVD [atherosclerotic cardiovascular disease] risk, we should be saying, “You have the disease. Here’s how much your plaque burden in the legs and the heart is, and here’s how I’m going to get you motivated.” Behavioral change starts with getting the person to have an emotional response—not a rational response, but an emotional response—to that issue.

A variety of things, whether it’s LP(a) [lipoprotein(a)] or other things, are going to change how we think of the biology of the plaque. Maybe the biggest discovery I see coming is how we think about diabetes. You’ve worked on this with others. There are agents that not only change your cardiovascular events but also reduce your weight and help you with diabetes. If you think about the global burden of those issues, those are the big areas.

Deepak Bhatt, MD, MPH: Those are all good ones. Amy, you’re next. What’s coming down the pike?

Amy Pollak, MD: I agree wholeheartedly. Screening is critical. We know from the decisions about aspirin for primary prevention and shrinking the population, who gets treated with aspirin for primary prevention based on USPTSF [US Preventive Services Task Force] recommendation changes, you’re using a coronary calcium scan. It can help risk-stratify. To your point, we’re identifying patients who have atherosclerosis. We need to be doing the same thing in patients at increased cardiovascular risk and looking for PAD as well.

Marc brought up the PCSK9 inhibitors and more aggressive lipid lowering. It’s been too long of not treating our highest-risk patients aggressively enough if we have these tools at our disposal. We’re not talking with patients about why we need to use these. You brought up the importance of diet despite everything else we’re layering on: trying to address food deserts, access to healthy food, all of the social determinants of health. As a community, as we’re emerging from COVID-19 and start to be together again in communities, it’s going to be critical to find safe ways to have patients exercise and be active, such as walking trails.

The last thought is regarding the microvascular disease. One of my other hats is with women’s heart health, and microvascular disease has certainly been part of how we view women’s presentation with chronic symptoms or an acute coronary syndrome. We’re at the beginning of understanding microvascular disease with PAD. My final thought is we have this imprint in our minds of the heart, brain, leg connection—the 3 legs of the stool—if we’re going to treat patients’ cardiovascular risk aggressively.

Deepak Bhatt, MD, MPH: You’ve made many different and good points. We’ll do a lot more as a community about microvascular disease. It will be primarily medical therapy based, but that’s going to be an area that’s ripe for further discovery. Marc, what’s exciting to you in terms of unmet needs, risks, and ways to address them?

Marc P. Bonaca, MD, MPH: Thank you, Deepak. Those are great comments. We’ve had a lot of trouble being successful in implementing lifestyle change with our patients. You have 15 minutes with the patient. It’s hard enough to prescribe drugs, but lifestyle change is really hard to do when it’s every 6 months in the clinic. There are new digital therapeutics out there that are helping people with cognitive behavioral therapy and other ways that have shown improvements. You can have patients lower their own hemoglobin A1C [glycated hemoglobin] and other things through lifestyle change. That’s an exciting avenue to interact with our patients in the digital domain. That plays into what Manesh said about implementation science. We need to invest the same resources and study how to move the needle as we do in the refined experiments that show efficacy and safety of the drugs. I look forward to more implementation science.

In the therapeutic domain a lot of things have been said. With LP(a), there’s a real relationship with peripheral artery disease and some very bad events. There may be an exciting avenue for tailored therapy in those patients who have an elevated LP(a). Finally, we’re further decoupling ischemic risk and bleeding risk with our antithrombotics and broadening the utilization of antithrombotic therapies, in terms of those perceived as high bleeding risk or who are at high bleeding risk, to offer more avenues. When you look at patient selection things, it’s always hard to say, “What if you’re at a high bleeding risk?” If you use antiplatelet monotherapy, then that thrombotic risk that Manesh talked about remains unaddressed, so finding new therapies is important.

Deepak Bhatt, MD, MPH: Those are all promising areas for the future. What do you think, Sahil? What do you put on your top 10 list?

Sahil Parikh, MD: As a coronary and peripheral interventionalist, I think the most vexing thing is that we’ve known for a long time that the critical inpatient is the highest-risk patient that I ever treat, whether it’s a stent or any other intervention. For the last 4 decades, we’ve gotten better at revascularization, but we haven’t altered the mortality curve. It’s because of a lack of understanding that the systemic things that Eric alluded to are the problem: the patient’s diet, mind, and stroke. Even though we’re taking care of their legs, we need to take care of the whole patient. With low-dose rivaroxaban, we may have an arrow in the quiver, and we just need to use more to bend that curve. That’s what I hope for. That’s what we’ve been waiting for all this time.

There are other areas, though. It seems as if every other day there’s an article about SGLT2 inhibitors becoming a panacea for every cardiovascular ailment we see. The application of that is specifically looking in these high-risk populations, trying to see which arrows in the quiver are going to bend that mortality curve. That’s where the field is moving. Yes, we’ll be innovating new technologies for the specific treatments, but we’re just fixing potholes; we’re not fixing the highway. Until we get that infrastructure fixed, we’re not going to bend that mortality curve.

Deepak Bhatt, MD, MPH: Both are important. You don’t want potholes on your drive to work, either. The potholes matter too, but the highway matters a lot as well. I totally agree. It’s always tougher going at the end of the panel because everyone has already said the good things already.

Eric Secemsky, MD: I’m checking off everything I can’t say.

Deepak Bhatt, MD, MPH: That’s why I’m giving you a couple of seconds. What’s on your list of things that are up and coming?

Eric Secemsky, MD: We start the conversation with polyvascular disease. We haven’t spent a lot of time on polypharmacy. Concerning all the things we’ve discussed; the therapies don’t work if the patients don’t take them. We’ve seen this in hypertension. More than 50% of people don’t have hypertension under control. If you go from 2 hypertension agents to 3, you double your risk of nonadherence. We have some amazing therapies available, but we need to get our patients to take them. We’ve saw some great evidence last year on polypills—the renewal of the polypill. Maybe we should be tailoring some of our therapy, so that list of 10 medical regimens that our patients carry around in their pillboxes are 1, 2, or 3.

We’re also going to see more device-based treatments for other conditions, like hypertension. We’re talking about renal denervation as an option to limit the pill burden and use another mechanism of reducing a cardiovascular risk factor that has great long-term risks. Bringing it back to the patient, we can do a great job creating these therapies, but they don’t work if the patient doesn’t take them. We need to do a little better job of getting an adherent regimen that a patient can follow long term. Marc, that ties in to your comment on implementation science and bringing it from the clinic to the home.

Transcript Edited for Clarity