Manesh Patel, MD

We’re going to move on to not just identifying polyvascular disease, but what to do about it. I’ll start with you, Amy. What do the guidelines from the ACC [American College of Cardiology] and the AHA [American Heart Association] tell us about managing coronary artery disease [CAD]? A bunch of new guidelines have come out lately at this meeting and at the last meeting. But let’s look at the ones pertaining to coronary artery disease and revascularization and that sort of thing?

 As you said, a tremendous amount has recently come out with updated guidelines. But a lot of the fundamental parts of how we treat cardiovascular patients haven’t changed. If somebody has stable symptoms, we’re focusing on optimal medical management. We’re trying to tease out patients who are going to be at the highest cardiovascular risks, obviously left main disease if someone is symptomatic or 3-vessel disease and seeking revascularization. We’re strategizing for patients who have very stable symptoms, who don’t have left main or 3-vessel disease for whom we’re doing medical therapy vs individuals who need to go to for revascularization.

The risk factor reduction approaches cannot be underscored in terms of the importance of having individuals on appropriate antiplatelet, whether it’s a layered antithrombotic, lipid lowering with aggressive LDL [low-density lipoprotein], cholesterol lowering using statins and PCSK9 inhibitors, among other therapies. Plus, blood pressure control, blood sugar, tobacco cessation. For all those risk factor reduction approaches, which are critical for patients who have polyvascular disease, they’re even more important. It’s striking that in the REACH [Reduction of Atherothrombosis for Continued Health] Registry, for patients who had had a prior ischemic event in the last 12 months, the risk of a future event over a 4-year period was staggering. It was a 25% for patients who have polyvascular disease, in terms of the mortality associated with these diseases. Patients who had diabetes and vascular disease also had extraordinarily high risk.

We have a large amount of tools to help patients and reduce this risk, but we’re not always using them as intensely as we should. In a diverse population, we haven’t touched much on health equity. There are tremendous health disparities in access to screening, medical care, and medications. We have a lot of work to do for all Americans to have access to these life-saving treatments.

That’s a great point. In the national dialogue, there has been a lot of talk about disparities. But we need a lot of action, so that’s very good. Beyond classic disparities based on race and sex, which has come up during the COVID-19 pandemic, there are disparities based on location. Rural care in the United States vs urban care. There are a lot of disparities as well.

Manesh, what are your thoughts? Amy did a good job mentioning therapies like lipid-lowering blood pressure. What about antithrombotictherapy? What’s the role there? And for coronary artery disease?

 As I started, I suspect that in the future there will be therapies for the inflammatory component, where many are testing. But right now, when somebody comes to clinic, I don’t think about anti-inflammatories for cardiovascular disease. I think about atherothrombosis. Obviously, for the athero part, there’s LDL lowering, and there will be some other agents there. Most people are saying, “Let’s get your LDL down as far as possible to control blood pressure, diabetes.” But as an interventional cardiologist, I grew up in a platelet-centric world, where more antiplatelet therapy was good and less put our patients at risk. Deepak you led some of the most important studies in this space, where we know we could add 1 or 2 agents. We started to understand that 2 is better than 1.

Recently, of course, we now know about dual-pathway inhibition. We talked about that. That’s thinking about the evolution from, let’s say broadly, vitamin K antagonist type of medication. It’s a very specific dose for antithrombotic therapy at the 10A level. We know that for 2.5 mg of rivaroxaban, we’re going to talk about some of those trial data. With aspirin, it might be dual-pathway inhibition. Now when I see the patient with coronary artery disease, the guidelines say to first make sure you treat the athero spot.

Then you have to have some antiplatelet therapy for chronic vascular disease for CAD. It’s usually aspirin and clopidogrel or aspirin. Obviously, we’ve seen those data. Most of our patients with coronary artery disease are getting all that in aspirin. We’re starting to see data about doing dual pathway or dual antiplatelet. Because of our stenting world, we were into dual-antiplatelet therapy [DAPT], but for chronic coronary artery disease we’ve got really good evidence now that dual pathway is a pretty significant improvement in their lifestyle. But that’s a change. To Eric’s point, I have to let go of what I learned for many years and relearn some things or convince my patients that this is the right thing to do.

Those are valuable points. To amplify the dual-antiplatelet therapy, everyone of the audience is familiar with that. Historically that’s been aspirin and clopidogrel, but then aspirin and clopidogrel aspirin and an anticoagulant. The dual-pathway inhibition specifically is referring to aspirin and what some call vascular dose for rivaroxaban, 2.5 mg twice a day of that particular dose. We have a few different options: antiplatelet monotherapy, dual-antiplatelet therapy, dual-pathway inhibition for the patient with the coronary artery disease. Eric, what about throwing PAD [peripheral artery disease] into the mix? How does that alter considerations toward antithrombotic therapy?

 I’m reflecting on the comments that Manesh made. We’ve had a bit of an identity crisis in the cath lab. We spent the late 2000s and early 2010s saying that we need dual-antiplatelet therapy in everybody for a long time. We did the DAPT study, and there’s some benefit. There are also some risks. We spent the last 5 years saying that we could probably get rid of Plavix, ticagrelor, prasugrel earlier on, especially for someone coming to the cath lab for a coronary stent. Now everybody wants to be off therapy earlier. There’s a balance there. It’s about what’s going to give you the best long-term benefit for long-term outcomes. We’re thinking a little less about the procedural side with the stents and more about the patient.

Now you throw on PAD. These patients have substantial risks of morbidity and mortality. We love talking about life and limb and keeping both going for these patients. But most patients, especially when they get more advanced PAD, have risks as high as 50% of dying or losing a leg in 1 year. Now we can do things really well in the cath lab. We can move away from the dual-antiplatelet therapy and think about dual-pathway inhibition a little more. When we think about the thrombotic risk, that’s when we can make the long-term benefit for patients for their limbs, as well as their cardiovascular disease and other processes.

I’ll remind the audience that our PAD population rarely dies from a limb-related event. It’s usually a heart attack or a stroke. That’s what we’re really treating these patients for. We treat their legs for quality of life, making sure they heal, but that’s not what drives their mortality. This focus now is on our safer procedures. We’ve got a better hold on how to keep our stents open, our balloons open. We’ve got to think about the therapy that works on the long-term outcomes for these patients. And it goes back to this thrombotic risk that’s added to their atherosclerotic risk.

A lot of valuable points that you made. For the audience, we’ll come back in the next segment with a detailed discussion about dual-antiplatelet therapy, antiplatelet monotherapy, de-escalation strategies, and dual-pathway inhibition. We’ll review all those data in some detail. But before we get to that, Sahil, I’d be interested in your perspective. How do we factor in other things? If the patient has diabetes or chronic kidney disease, how does that affect your decision-making in regard to patients with CAD, CAD and PAD, or just cardiovascular disease?

 It heightens my concern. In our practice nowadays, 30% to 35% of patients coming to the cath lab have diabetes. In the PAD population, it’s enriched perhaps 2-fold, particularly the critical limb population that many of us take care of. In those patient populations, it’s clear that either renal disease or diabetes is highly likely to be prevalent. Consequently, it will heighten our concern about their atherothrombotic risk.

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Expert cardiologists discuss CAD guidelines and approaches to management of patients with polyvascular disease.

Guidelines and Management of Patients With Polyvascular Disease

Sahil, let’s say you’re in the catheterization lab, and you’re treating somebody for CAD [coronary artery disease] but you happen to come across the fact that they have PAD [peripheral artery disease]. Maybe you’re using routine ultrasound, which is good practice. You see a bunch of femoral plaque. Is it your job then to take care of the PAD aspects of that patient? What do you do with that? Do you then own that issue?

 Yes. In my practice, I’m usually the patient’s cardiologist and vascular specialist wrapped in 1. If they have a cardiologist, then I do only the vascular job.

 Yes. It’s incumbent upon us to identify a polyvascular patient for whomever the referring physician might be in my own practice or someone else. Clearly, we’ve all already emphasized that this is a marker of high risk. My antennae are always up when it’s clear that there’s a polyvascular patient. The staff does rock, paper, scissors to not be in my room because we tend to have the highest burden of atherothrombosis systemically in all our patients, and they have the most complex disease. We tend to do some of the most complex procedures as a consequence of that. It’s very important to give that feedback to not just the referring doctor but the patient. And to demonstrate to them that they you have a systemic illness that’s clearly present in a lot of places, perhaps in places they didn’t realize. For us, that means we need to be more aggressive about your secondary medical prevention. It seems like a lot of different categories of medical therapy. That’s critically important.

 Deepak, 1 thing that’s interesting about our conversation is we’re talking about screening and identifying polyvascular. I think labeling the patient with this disease and saying, “This is what have,” is important to engage them and obviously our entire health care team. But why is that you should get a colonoscopy at age 45? Nobody questions the value of that. The most common condition in medicine leaves the most burden of events. We’re still a little hesitant to push for studies and things that identify athero. If we want to eradicate the most common thing killing people, we want to bend the curve of cardiovascular disease. Why are we saying that if you came to the cath lab, we shouldn’t know if you have PAD? We shouldn’t know if you have carotid disease. That’s a little on the edge. I get it. But I’m saying that because for cancer screening, we do all kinds of things. To highlight, we haven’t changed cancer mortality in 50 years despite amazing therapies. But they’re very personalized. We’re changing cardiovascular mortality, yet we’re scared to go look for more vascular disease.

That’s a really interesting comment. It makes me think deeply about a lot of issues. Part of the hesitancy in cardiovascular medicine is that we’re so evidence based. If there isn’t a trial proving that a screening technique works, we say, “We can’t do that.” But what will change things isn’t necessarily doing to do a bunch of large trials. Maybe we will. I hope we do. But patients, even healthy people, are going to change it. It’s the cost and availability of screening, which is just there for the masses. People can get a carotid ultrasound without the doctor even being in the loop, for example. Or a CT scan of their coronaries. They’re going to do it whether there’s evidence or not. Many times, we’ll be left with the question of what we do with those data in the absence of clinical trials showing that strategy. It’s happening with wearables—maybe it’s a good idea for patients to detect A-Fib [atrial fibrillation] on their own. Maybe I don’t think it’s a good idea. But it doesn’t matter what I think. It’s probably better. I’ll help, as a community, to steer that technology so they’re providing value to patients and, more broadly, the health care system.

It’s been a great discussion on polyvascular disease. I hope the audience enjoyed that.

Dr Sahil Parikh and other experts discuss engagement of cardiologists in patients diagnosed with polyvascular disease and challenges in screening patients.

Provider Engagement and Screening

Amy, now that we’re talking about polyvascular disease, certainly when it is identified in the clinic through history and physical, no one is going to argue—well, hopefully no one is going to argue—the value of that. Maybe we still have to convince the audience that there’s value in that. But a question that sometimes follows is, should we be screening for that? There are a lot of CT machines out there. Should we be doing random CT angiography from head to toe on everybody or on select people? What about things like ankle-brachial index? Should everybody get 1 of those? What about screening for carotid disease? The question of screening comes up, and the potential benefits of identifying disease early, but the potential risks of breaking the health care system bank by ordering a bunch of tests on people who are asymptomatic. Potentially we’re identifying disease, but should you do a procedure if you find some mere blockage? Going down that cascade. What’s your recommendation with respect to polyvascular disease, PAD [peripheral artery disease], cerebrovascular disease, and any screening absent symptoms? Obviously if someone is complaining of bad pain in the leg, or chest pain, that would appropriately prompt testing in the asymptomatic but high-risk individual.

 This is an outstanding question. I’m sure everyone agrees that this is something we face day in and day out in our clinical practice. It’s an important area to focus on nationally as we try to care for our patients with vascular disease. But if we take a step back, your point is a good one. If someone is symptomatic, then our path is pretty clear. But as we know, only about 10% of our patients with PAD are going to have this classic intermittent claudication. Often, we don’t ask patients about leg symptoms and whether they’re having more change in their exercise capacity and leg fatigue, some of these other atypical symptoms, or not having any symptoms because they’ve curtailed their exercise ability. Having that expanded discussion with patients to get a sense for how active they are and if they’re having any limitation in their ability to walk is part of it. Because then it’s a diagnostic test as opposed to a screening test in terms of doing an ABI [ankle brachial index test] to diagnose PAD.

The other part is the physical exam. We all have this kind of common refrain of making sure we take the socks off and check people’s pulses. Josh Beckman loves to remind folks to take the socks off in physical exam, and that’s critical. It’s easier in Florida where I live because people wear flip-flops. It’s harder in Minnesota, where you have to take off boots and socks. Nonetheless, it’s important to do that physical exam, not only doing the distal pulses but a thorough vascular exam. Because that’s no cost other than our time, and it can provide a lot of information. That would be a diagnostic test as opposed to a screening test for ABI.

We’re doing a history and physical, expanding that for a focus on vascular disease and the REACH [Reduction of Atherothrombosis for Continued Health] Registry with the work you’ve done. You know these data well. But it was striking that in patients who had symptomatic or clinical coronary artery disease, 30% had polyvascular disease. That’s a huge percentage and probably just the tip of the iceberg. They might have undiagnosed triple vessel disease or undiagnosed PAD. But of the patients with PAD in the REACH Registry, 60% had polyvascular disease. Thus, there’s a lot of disease if we’re looking for it.

There needs to be a change in how we approach screening. Identifying these highest-risk patients, the ACC [American College of Cardiology] and AHA [American Heart Association] have advocated in guidelines for years to screen patients who have diabetes, tobacco use, using different age criteria, patients who had known cardiovascular disease. Unfortunately, there’s this gap between the US Preventive Services Task Force and having adequate data to support screening. There’s a path forward where there’s a change in the screening guidelines, and hopefully we can see that in the near future.

Those are terrific points. Maybe it’s because you’re from Mayo Clinic. It made me think of an article from many years ago in Mayo Clinic proceedings, in the catheterization lab, where they identified some strategies to screen patients for PAD. I wrote the accompanying editorial. At the time, it was really insightful that they were thinking about these things. Eric, what do you do when you’re in the cath lab for a patient with coronary disease? Is there anything you do to see if they have disease elsewhere?

 The modern-day cath lab has changed a lot. We use a lot more vascular ultrasounds. That’s always your first clue. If it’s going into a frontal artery to get access, you’d see plaque in the frontal artery. Even for a coronary case, you’d know that this patient is a polyvascular patient. Turning on your fluoroscopy machine, you can already see that the vessel wall is calcified. We talk a lot about aortic pathology, which is related to this atherosclerotic process. Same thing with the mesenteric arteries, the renal arteries. You already get a lot of glimpses of this when you go in and do a procedure for a patient without even thinking about working that patient up for this information to have it in front of you at the table.

But the most important thing—the conversation we have before the patient comes on the table—is what are this patient’s risk factors? The conversation we have is always: do they have diabetes? What’s the renal function? What’s the strength of their heart or their ejection fraction? All of that gives you some insight. It’s not only what you’re predicting to see with the coronary disease, but the overall global risk and how you want to treat that patient. We take home that information, we do the procedure, we treat the patient for their coronary disease, but we use that to plan how to move forward. What are our next steps? We’ve already had 1 problem if they’re in the cath lab. How do we prevent the next problem? We put all these pieces of information together to make the right plan for that patient.

You made a lot of valuable points. You mentioned heart failure. That’s something else to consider. Oftentimes, patients with heart failure—especially in the cath lab, where there’s an ischemic basis—have severe coronary disease but also severe cerebrovascular and peripheral artery disease. Those issues may factor into whether they are or aren’t good surgical candidates, so it brings up a lot of things.

The other thing I’ll bring up is my own pet peeves in the cath lab. Every patient should have their blood pressure checked in both arms. I’m surprised how many times there’s a patient with angina, but no one has checked the blood pressure in both arms. That bothers me when that doesn’t happen routinely, and it still doesn’t happen. It happens less with automated blood pressure cuffs than it used to. It’s a basic thing but often overlooked.

You mentioned taking off the socks. That’s important. In the cath lab, the socks are usually off, but then they’ve got bootees to keep their feet warm. It’s important to feel the pulses. You know, the PT [posterior tibial] and DP [dorsalis pedis] pulses should be tested but documented as well. That used to be something that was always the cardiology fellow’s job or intervention fellow’s job to do. You always check the groin, listen for bruits, that sort of thing. But those things fall a little by the wayside. As we’re doing more radio, sometimes the patients are wearing pants, so no one has taken off the socks or the pants or anything, listened to femorals, or felt the feet. It would be nice to bring back those skills.

Dr Amy Pollak and other experts discuss their recommendations for screening for CAD and PAD in asymptomatic patients.

Screening for Polyvascular Disease

 titled “Expert Perspectives on Managing Polyvascular Disease and Coronary Artery Disease.” I’m Dr Deepak Bhatt from Brigham Women’s Hospital and Harvard Medical School in Boston, Massachusetts. It’s a real pleasure to be with you today. I’m fortunate to have 5 good friends and distinguished colleagues with me. Let me start with the far end of the table. Dr Manesh Patel is the chief of cardiology at Duke University Medical Center in Morrisville, North Carolina. Welcome, Manesh.

I’ll move on to Dr Amy Pollak, who is the director of cardiac subspecialties at the Mayo Clinic in Jacksonville, Florida. It’s great to have you here.

Dr Marc Bonaca is a professor of medicine and the director of vascular research at the University of Colorado in Aurora, Colorado. Welcome, Marc.

Dr Sahil Parikh is an associate professor at Columbia University [College of Physicians and Surgeons in New York, New York]. Dr Eric Secemsky is the director of vascular intervention at Beth Israel Deaconess Medical Center in Boston, Massachusetts. Today, we’re going to discuss treatment of polyvascular disease, in particular coronary artery disease and associated conditions such as peripheral artery disease [PAD], cerebrovascular disease, etc. We’re going to talk about dual-antiplatelet therapy in that context. We’re going to talk about dual-pathway inhibition in that context. For anyone not familiar with that term, we’re going to explain exactly what that means. We’re also going to share what we consider to be the optimal duration of that—a very controversial topic—and the rationale for switching between different forms of therapy. De-escalation for single antiplatelet therapy, escalation from single antiplatelet therapy to dual antiplatelet therapy, where does dual pathway inhibition fit into that. There are lots of different, sometimes overlapping, topics that will hopefully shed light on and inform your clinical practices.

With that, let’s get started with our first topic, which is a discussion of polyvascular disease and coronary artery disease. I’ll turn to Dr Bonaca and ask, what exactly is polyvascular disease? I imagine many people in our audience haven’t heard the term. Before we talk about what we do with it, maybe it would be good to say what it is.

 Thank you. This is such an important topic, and it’s emerged in the last 10 to 15 years. Deepak, I learned the term from you from the REACH [Reduction of Atherothrombosis for Continued Health] Registry. Although we know there are different manifestations of atherosclerosis—coronary, cerebrovascular, and peripheral—and that those patients are all high-risk, they share an underlying pathobiology. There are a group of patients who manifest symptoms in multiple vascular territories. They have coronary disease and peripheral disease, or cerebrovascular disease and coronary disease. They’re at extremely high risk. No matter what data set you look at, it’s been recapitulated many times from your initial work that after you adjust for all the other differences, they’re at 50% to 80% higher risk of having bad things happen, like atherothrombotic events. They’re really emerging as a unique population of patients who are at extreme risk of irreversible harm events of the heart, limb, and brain. Some of that depends on where they manifest symptoms, but they’re all extremely high risk.

Those are really valuable points for the audience, that polyvascular disease and its identifications are important for those patients who are high risk. Later, we’ll get to what we can do about that. Manesh, is it fair to lump all those things together? For coronary artery disease and peripheral artery disease—I’m going to throw in cerebrovascular disease—are they more of the same? Or are they different beasts?

 That’s a great question. That’s something we’ve been trying to understand even better. Our understanding of the biology is that atherosclerosis, as we’ve often used the term, is an inflammatory atherothrombotic event. In all these different vascular beds, patients will have downstream events. But we’ve learned that some of our patients with PAD who haven’t had coronary events probably have an overexpression of atherosclerosis in their lower extremity. When we did some of the PAD studies that many in this group have been involved with, we saw that concerning coronary disease, we often think of it as the same disease. I like to think of it as different phenotypic manifestations of the same disease. But if you see a patient in clinic who’s 65, 70 years old with peripheral vascular disease and they haven’t had a coronary event, that doesn’t mean they don’t have coronary atherosclerosis. It means they’re expressing that risk in their lower extremities much as somebody might do with stroke.

Why do they have it in different beds? That’s an unusual question that I don’t think we know the answer to. We know that atherosclerosis starts in the lower extremities, in the iliacs. There’s wonderful work by Dr Val Fuster and others that starts to show us the natural disease course. On average, for the clinicians and people I see in clinic, I think about polyvascular disease as how many places is this really important manifestation happening. Is it in the legs? Is it in the brain? Is it in the carotids? I’ll even go further. Is it in the kidney? Do they have diabetes? Do they have multivessel coronary disease? All these are risk factors. One might say 

 is usually used for vascular beds. We don’t think about the kidney and atherosclerosis as much. We don’t use diabetes as a marker as much. But I’d be thinking about my patient who has those conditions also as polyvascular.

Those are some insightful comments. Diabetes, for sure. That definitely amplifies risk even beyond the presence of polyvascular disease. Your comment about the kidney is very interesting. Polyvascular disease was initially defined in the REACH Registry. But concerning kidney, why shouldn’t that count? Dr Eugene Braunwald made that point in an analysis from the SAVOR-TIMI 53 trial. Your current faculty member Dr Tony Gutierrez looked at that as an additional vascular bed. It’s not the traditional coronary peripheral, cerebral. What if they do have microalbuminuria, macroalbuminuria? Does that count as an additional risk amplifier, as you’re rightly suggesting? Yes, indeed it does. That’s a really good point.

Drs Marc Bonaca and Manesh Patel provide an overview of Polyvascular Disease and prevalence of coronary artery disease and peripheral artery disease. 

Manesh Patel, MD

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