A Multidisciplinary Overview of Peripheral Artery Disease: Part 2

Podcast Transcript

Announcer:

Welcome to Cleveland Clinic Cardiac Consult, brought to you by the Sydell and Arnold Miller Family Heart, Vascular and Thoracic Institute at Cleveland Clinic.

Scott Cameron, MD, PhD:

One of the things we heard about, this is one extreme where a patient requires a procedure in order to restore blood flow, but for those patients who might have peripheral artery disease and need risk factor reduction and maybe supervised exercise training to get them out of pain, I wonder, Dr. Laffin, if I could come back to you because we know that all patients with peripheral artery disease should be on an antiplatelet therapy consisting of either aspirin or clopidogrel. In most cases, they should be on a statin medication. They should be on an ACE inhibitor or an angiotensin receptor blocker according to established guidelines. Those last two medicines, of course, are helpful for blood pressure. Could you maybe give us a little bit more information on your section's particular expertise for those patients whose LDL bad cholesterol really doesn't get down to target or they're having a lot of off-target effects, as sometimes find patients are hesitant to take statin medications and there are other classes of medicines we can use. I wonder if you could please tell us about those.

Definitely. So as many people know, peripheral arterial disease is equivalent when we think about it to coronary artery disease and these are secondary prevention patients, so we need to use all the tools in our toolbox to actually lower LDL cholesterol. That includes maximally tolerated doses of statins as you alluded to. That's the gold standard. But there's much more available. We have medicines that have been around for quite a while, like ezetimibe, brand name is Zetia, which you can take, lowers LDL cholesterol by an additional 20 to 25 percent. There's a newer medicine called bempedoic acid, which is also oral, which lowers LDL cholesterol also by 20 to 25 percent. There are injectable medicines, specifically monoclonal antibody PCSK9 inhibitors, and the names for those are alirocumab and evolocumab, and they have a very prominent reduction in LDL cholesterol, almost 60 percent in most cases. And those are oftentimes a good scenario in folks that have statin associated muscle symptoms or an intolerance.

And then a newer medicine as well is called inclisiran, and that's a short interfering RNA. And the nice part about that is that's an injection you can get every six months in the office. So for those patients that may be more likely to be non-adherent, is a good potential option. And that lowers LDL cholesterol by 50 percent. And what we try and target is LDL cholesterol at least less than 70, but actually more recent guidelines, particularly European guidelines, pushing that even lower to LDL cholesterol less than 55. As I like to say, lower is better, lowest is best when it comes to LDL cholesterol reduction.

Scott Cameron, MD, PhD:

That's always a question, how low do you go? Patients sometimes say, isn't that a little bit too low, doctor? What do you respond when you hear that question?

Luke Laffin, MD:

So I tell them about the data from the Fourier and Odyssey trials, right? Looking at the difference between alirocumab and evolocumab. And to refresh folks, with alirocumab, they thought, well, maybe we are going too low with the LDL cholesterol, so let's dose reduce. And guess what? Their hazard ratio wasn't as good. Okay? So actually it doesn't look like it was quite as effective in the trial, when both medicines are pretty equivalent, but lower is better in that scenario. In all practicality, if we get into the low single digits for LDL cholesterol, then I might say, yes, you can cut your statin, Rosuvastatin, from 40 to 20, but we're definitely not getting people off of it at that point.

Scott Cameron, MD, PhD:

Yes. Wonder, doctor, where I'd like to touch base a little bit on an additional class of medications that our vascular physicians use quite often, antithrombotic therapy consisting of anticoagulants. Now is it turns out that someone who has peripheral artery disease, so disease in the arteries in the leg, if they also have heart disease with or without disease in their brain, if it's a patient that's had a stroke, there is another medication, rivaroxaban, in a dose that I think some physicians may not be familiar of its availability and some patients may not know about it. Tell us a little bit about that medication and how we've used that to optimize care and prevent heart attacks and strokes with people who've got narrowed arteries in the leg.

Teresa Wu, MD:

Of course. So you mentioned vascular disease in more than one area. And so we call that polyvascular disease sometimes. And this is a concept that we use to define vascular disease in more than one bed. And as you mentioned, this is important because we know that this is associated with an even increased risk in things like heart attack and stroke. And so when it comes to managing these patients, we have actually great data on the use of specific agents. And so you mentioned the rivaroxaban, 2.5 milligrams actually is the dose that has been studied particularly in this population.

So rivaroxaban traditionally has been used as a blood thinner, as an anticoagulant, to treat patients with blood clots. But more recently has actually been studied in patients with peripheral artery disease, and specifically in those who have both peripheral artery disease and also coronary disease. And that was studied in the COMPASS trial. And what they found was actually a significant benefit in the use of the rivaroxaban at a dose of 2.5 milligrams in conjunction with aspirin. And particularly the benefit was shown in patients who had disease in multiple beds, so for example, a patient with coronary and peripheral vascular disease. So that is something that I have seen more providers use, I personally use in my practice, and so it's a great tool to have in our toolbox.

Scott Cameron, MD, PhD:

I just wonder as we sort of come to the close on the medications, I think we're almost exhausting the amount of medical therapy we're offering, but you can see that there's a lot more available now than there was even six years ago. Dr. Nanjundappa, patients who've got narrowing arteries in the leg, they've gone to Dr. Laffin, they've gone through supervised exercise training, they're still with severe pain. There's another class of medications that we sometimes use called the phosphodiesterase inhibitors. Sometimes they work, sometimes they don't. I wonder if you could briefly tell us a little bit about your experience with that, and then maybe segue into what your experiences have been when they've failed supervised exercise training, they've failed maximum medical therapy that may include a phosphodiesterase inhibitor. How do patients feel if they've had a stent placed in the appropriate area to restore blood flow? Do their symptoms disappear or do you find that you can sometimes use that phosphodiesterase inhibitor to prevent them needing a procedure?

Aravinda Nanjundappa, MBBS, MD:

That's a great question, Dr. Cameron. I think from the beginning when I see a patient with peripheral artery disease, especially if it's SFA disease, we do start them on the phosphodiesterase inhibitor with the main thing is the cilostazol, which is also called pletal. The doses come in a hundred milligrams twice a day. Sometimes the patient says, I've tried before, I can't tolerate. Sometimes they get a little bit of diarrhea and they have symptoms of heart failure, then I may go down to 50 BID. The absolute classic contraindication for cilostazol is patients who are symptomatic with heart failure with class three, class four. If they're not symptomatic, I tend to give them the same dose of a hundred BID and tell them, you may have some GI soft stool or GI upset, but most can tolerate. And majority will tolerate. And the trials, what they showed is if you treat them with a hundred BID, takes about eight weeks to kick in and then one more month, maybe at 12 weeks, they start to see the difference. The main stay of treatment is cilostazol to help patients with claudication. It's got a vasodilatory effect and a thrombotic effect, so multiple benefits. And the claudication distance, if I remember the trials, it went from a hundred meters to at least 150 meters. So you're doubling the one and a half times the excess capacity.

Aravinda Nanjundappa, MBBS, MD:

But sometimes they don't tolerate. Sometimes if it's an aortoiliac disease, despite pletal, they're not able to achieve what they want to do. And for each person, claudication is different. For somebody who's a couch potato, maybe he can't get out of the sofa to walk to the bathroom. That's his lifestyle limitation versus a person who is running marathons. For him, if he can't walk a hundred meters, that may be lifestyle limitation. And depending upon the work the person does, we just had recently seen a patient who lays the tar on the street and he can't put the coal on the street to make the tar roads. So for him, the limitation may be more aggressive. So for such patients, we do offer angioplasty and stent. There's a wide range of treatment that's available and sometimes we differ each other in how we see which is the best option. In my opinion, patients can get a balloon angioplasty. It's very safe and we have the medicated balloons called the drug-regulating with the balloon. Their patency is almost better than a bare metal stent. So we treat with a balloon angioplasty followed by a drug-regulating balloon with a long inflation results, you have a better patency of the artery, better resolution of the symptoms. We are talking about above the knee. Below knee, we don't have much data on the drug-regulating balloon.

If the balloon angioplasty fails repeatedly or there is a longer area of dissection than maybe stents.

Aravinda Nanjundappa, MBBS, MD:

But in terms of stents, I try to shy away from the areas of common femoral artery. That's an area, it's like a very easily treatable by surgery. Also, when the patients bend down, it may crush. Arteries behind the kneecap is not best treated with stent unless it's really needed. So foregoing these two areas, most of them can be treated with a stent. And with the drug-regulating balloon, Cleveland Clinic led a lot of the clinical trials. The patency anywhere can be between 74 percent to up to 89 percent. When you compare that with the balloon angioplasty itself, enlargement analysis can be as low as 42 percent to 60, 70 percent. So, you have an added benefit of 10 to 20 percent just drug-regulating balloon. If it's short segment and then you stent, you can get up the patency up to 80, 90 percent. But stents, when they go down, it's trouble. So we still try to avoid putting stents unless it's really needed, especially for the scenario explained claudication, balloon angioplasty, probably good.

Scott Cameron, MD, PhD:

Okay. Well, just in closing, Dr. Quatromoni, I wonder if you could give us a little bit of your experience with the collaborations that we've had in Cleveland Clinic. So, one of the things we're really blessed with in the Heart, Vascular and Thoracic Institute is multidisciplinary care. And I know certainly I've had this situation, and so have some of my peers, a patient has been referred to vascular medicine that clearly needs imminent surgical intervention. But that's okay because we're very collaborative and similarly, vascular medicine offers the doctor of the day consultation line and sometimes there's a very medically complex patient and you've gotten them over to us. Can you maybe tell us a little bit about your experience with this cross collaboration that we have?

Jon Quatromoni, MD:

This is a very unique feature of Cleveland Clinic having access to such a wide variety of talented colleagues, and it really makes it a pleasure to work with everyone, particularly for patients where they may be driving three or four hours to see me, or maybe they came into your office and we realized, hey, we need another opinion here. We need to kind of sort the situation out. I think having that option where we can just literally call up and say, hey, can you squeeze this patient into your office? They can walk right down the hall and kind of get the care that they need in an expedited fashion. In the outpatient setting, if it's something that's more urgent, we can bring them into the hospital and engage everybody in the inpatient side as well. But just having that as an option, I think, at least reassures me that we can get the people that we need in a timely fashion in that setting.

Scott Cameron, MD, PhD:

Okay. Well, just to wrap up, I'd just like to thank you for joining us this evening to talk about peripheral artery disease. And once again, just to identify Dr. Luke Laffin, from the section of preventive cardiology, offers many things for risk factor reduction as well as supervised exercise training. Dr. Wu from vascular medicine offers comprehensive screening as well as imaging as well as maximum use of antithrombotic medication. Dr. Nanjundappa also cardiologist and offers percutaneous intervention. And then Dr. Quatromoni sort of wears the crown jewel because he's able to do all things, medical management, percutaneous intervention, as well as surgical management. Thank you so much for joining us.

Announcer:

Thank you for listening. We hope you enjoyed the podcast. We welcome your comments and feedback. Please contact us heart@ccf.org. Like what you heard? Subscribe wherever you get your podcasts or listen at clevelandclinic.org/cardiacconsultpodcast.