The Role of Factor Xa Inhibitors in the Management of CAD/PAD - Episode 11
Deepak L. Bhatt, MD, MPH: Vamsi, there is one thing we still haven’t squarely addressed. I think you nicely, intuitively, described how to identify risk, and you use data to do it. So we can figure out who’s at high risk. But who should pull the trigger? Should that be the primary care physician, or should it still be a cardiologist or vascular medicine specialist who then lets the primary care physician know of their rationale, know to watch for bleeding, and know to watch for other sorts of issues?
Vamsi Krishna, MD: I think, even among us, we have such different practices. We have a universal health care system, we have 2 university systems, and then a large Catholic-based system. And so I think the system is really going to help define what the best practice is for that area. I think, for example, if it’s a multispecialty group where primary care providers are in the same area as the cardiologists, a lot of times the primary care physicians feel very comfortable prescribing it.
Our current practice is such that primary care providers aren’t getting a lot of exposure to their cardiologist. I think there’s a lot of angst in the community for a patient; they’re not afraid of the data, they like the data, but they’re afraid of the bleeding. Who’s responsible if there’s a negative outcome? That’s some of the feedback I get from some of my primary care providers. Luckily, I’ve been able to do a lot of talks and education for them to help them understand that it’s actually quite simple. A majority of our patients in our south Austin, Texas area are at high risk. And so it’s really about who shouldn’t get it, helping them identify those things, but I really think it’s about the system in place.
I will say there’s something I really strongly went after, and it’s done really well. I’m head of the wound care area in south Austin, and the data, especially in PAD [peripheral artery disease] and in critical limb ischemia, show there really are not great guidelines outside of some hypertension therapies, some statin, and aspirin. There’s really not a lot out there, and now we have a therapeutic option that has reduction of limb amputation, reduction in revascularization that we have not seen in any other choice. There are really clear reasons that we try and save a limb, it is one of the most important things. And so I think from that standpoint I’ve been able to get a lot of physicians, even podiatrists and local wound care people, prescribing it because of the end goal of what we’re trying to do.
Deepak L. Bhatt, MD, MPH: You reminded me, I think you spoke quite eloquently about the stroke reduction, but there was also an important reduction in COMPASS in peripheral events. Do you want to expand on the exact findings?
John Eikelboom, MBBS, MSc, FRCPC: Yes. And this goes back to your comment earlier about Jagat Narula, MD, PhD, and his work. But in COMPASS, we found that the reduction in coronary events was of a magnitude that was similar to that in ATLAS ACS-2. There’s no question that this combination worked in coronary disease. The treatment effect perhaps is a little more modest in the coronary circulation. But this was this very big reduction in stroke we’ve talked about, 49% reduction in ischemic stroke, and a reduction in peripheral acute limb events of a similar magnitude, around a halving of the risk of acute limb ischemia and of amputation. It’s really an unprecedented reduction in these very serious events, and for the vascular patient who’s got peripheral artery disease, this is a compelling rationale to consider this treatment.
Deepak L. Bhatt, MD, MPH: And who does that in Canada, by the way? What sort of physician does that fall to?
John Eikelboom, MBBS, MSc, FRCPC: Well, in Canada it is probably like elsewhere, it’s a bit of a mix, but internists play a big role. There are some vascular specialists, and family physicians. And this is also why I think while family physicians may be cautious about this, this is going to become their responsibility because there is no way that the specialist clinics can handle all this.
Manesh Patel, MD: I would say the same. It is going to be system-based for sure. But another way of thinking about it is, if we didn’t talk about this disease state for a second, and I said somebody has atrial fibrillation and you’re going to anticoagulate the patient, are you sending them to an electrophysiologist to make that decision? You’re certainly not sending them to cardiologists any more. You’re making that decision. And the bleeding risk, one could argue, is not smaller, it’s larger. It’s that you’re worried about a stroke. Now, I just told you that this patient has a 50% reduction in stroke and a 50% reduction in limb events if they have vascular disease, or even if they don’t.
I agree with you because the family practice doctors, and our own primary care doctors have said this, they have to get comfortable with it. The bleeding has to be managed, the dose is lower, but the magnitude is pretty powerful. And if you have the high-risk patients, I would say you should feel comfortable at least having the conversation, or starting to think about which patients might get that therapy.
Eventually it’ll be like dual antiplatelet therapy. When that first started it was very much, “Oh boy, cardiology better tell us about these,” and even that got me to thinking about my 2 antiplatelet therapies. But you can imagine that that’s going to diffuse.
Vamsi Krishna, MD: This brings us to the whole greater point of all these risk reduction therapies that we have available. We have many. We have these new antidiabetic drugs, and I heavily believe in the data on the SGLT2 [sodium-glucose cotransporter 2] and GLP-1 [glucagon-like peptide-1] agonists. And yet the cardiologists I speak to say, “Well that’s not my responsibility.” And then say, “But the data show stroke reduction, MI [myocardial infarction] reduction, and there’s a 3-point MACE [major adverse cardiovascular events] outcome; and now look, we have credence data that show that there’s even renal protection and heart failure reduction.” So who’s responsibility is it? It comes back to the point of, I think there are a lot of great things out there, and we have to prioritize to each patient. Maybe we have time to say, “Hey, these 2 things are what we’re going to focus on during this visit.” What’s becoming challenging is who takes responsibility for it. And I think the better we can organize the societies in saying these are guidelines, these are class 1A and 1B indications that we should be utilizing it, the easier it’s going to be say, “Hey, we should just implement this in our system.”
Deepak L. Bhatt, MD, MPH: Well, I think the more eyes on the patient, the better, if we talk about high-risk patients. Perhaps not the real low-risk patients, that might lead to unnecessary testing. But in the high-risk and very high-risk patient, whose responsibility is it to ask for the SGLT2 inhibitor, for example? It could be primary care, it could be cardiology, it could be nephrology, it could be endocrinology. I think it’s all their responsibility because they’re all going to see patients at different times in different stages of their disease projection. And I think that with respect to SGLT2 inhibitors in particular, this is going to be an uptake among cardiologists in using these agents. It’s already starting where there’s a lot more cardiology comfort, certainly in primary care.
Vamsi Krishna, MD: It’s taken a longer time, given that the datasets have been available for some time.
Manesh Patel, MD: I think this is one of our messages. I live in the south of the United States, and change is hard sometimes and it takes a while, and I’m sure it’s that way the United States in general or all of our countries. But if you think about this year, 2019 was the first year that new starts for anticoagulation for atrial fibrillation were greater than 50% novel oral anticoagulants or non-vitamin K agents.
So in 2019, greater than 50% of the people worldwide are getting the new therapies, and by and large all 4 therapies reduce stroke, or at least have similar rates of stroke reduction, but also reduce intracranial hemorrhage and reduce fatal bleeding. That signals toward benefit, and before they started we all said, wouldn’t be nice to have a finger prick and get a drug?
The data started to come out in 2009, so 10 years of lives that could have been affected. COMPASS is now out. It’s certainly not going to be for everyone, but I would say it’s another example with SGLT2 inhibitors. Most of what we’re doing here today is to try to reduce that gap, that comfort, in saying, “There’s now evidence.” You’re going to have to try it in someone. How do you try and get comfort in it and then move on?
John Eikelboom, MBBS, MSc, FRCPC: I think it should be much faster with COMPASS, at least with atrial fibrillation. You had warfarin, so you had something that worked pretty well. No question, it still took a long time. But with the COMPASS regimen, especially for some of these super high-risk patients….
Manesh Patel, MD: Certainly for these carotid patients, limb patients, polyvascular patients, I would argue right now you’re right, we don’t have a lot of other things, unfortunately, whether it’s amputation or procedures. Every year I say this, every year in the United States we have more amputations than all the wars combined.
Deepak L. Bhatt, MD, MPH: That’s a very sobering statement when you put it that way.
Manesh Patel, MD: So there’s an opportunity to make a difference in things people care a lot about.
Transcript edited for clarity.