Amy Pollak, MD

This has been a great program. I’ve learned a lot. We covered lots of ground about antithrombotic therapy, coronary artery disease [CAD], and peripheral artery disease [PAD] in general. Let me turn to our distinguished panel for some closing thoughts. I’ll start with you, Manesh. Any final points [that] you want to make for the audience?

Deepak, it’s been fun and exciting. It’s fun to talk to people about evidence for the things we see. We’ve learned over the last decade is that vascular disease unfortunately is still the leading cause of cardiovascular mobility issues and mortality. As we have more options, which is a good thing, we have to get the right dose for the right patient at the right time. Some of that is understanding the risk and the risk benefits that we’ve talked about. Concerning patients with polyvascular disease, patients with broad thrombotic risk, it’s important to understand how you can make them have better outcomes. We’ve talked about that today. Hopefully it’s something that people will take home.

 I agree. It’s been a wonderful panel. I’m thrilled to be part of this. My take-home message would be to focus on identifying these polyvascular patients. Because they’re such high-risk patients, it’s important not to be focused on the coronary artery disease. But if patients have coronary artery disease and vascular disease in another territory, then that’s the pinnacle of our risk. Diabetes on top of that is going to be at that highest cardiovascular risk, so we need to talk with our patients about the fact that they’re at a higher risk and how that guides our recommendations for changing medications. Oftentimes patients can be resistant, understandably, to wanting to add another medication. But part of patient-centered decision-making is educating them that this is why that goes a long way.

We need to educate the medical community about those risks that identify polyvascular disease, diabetes is a real risk amplifier. Great points. Eric, any closing thoughts?

 This was a fantastic discussion. For everyone watching this, it’s important for us to not be fearful of making a change in our practice. We’ve been set in our ways for a long time, but we’ve had these accumulating data. It’s time for us to be open-minded about making changes that benefit our patients. We’ve heard today that there are many agents that can optimize long-term cardiovascular and limb-related risk outcomes and improve the care for our patients, so it was a great discussion.

Absolutely agree and Sahil, any final thoughts?

 That’s really important. What Eric just said is that we’ve been in this mode of using dual-antiplatelet therapy for extended amounts of time with very little evidence, particularly in the PAD population, which is the predominant part of my practice. It’s great that we have strong evidence to support the use of dual-pathway inhibition. We need to get the message out to our referring doctors and our patients that this is the way forward to optimize the risk.

Terrific. Marc, you’ll get the final word.

 It’s been an honor to be part of this panel. We’ve learned that we have a gap in terms of the evidence and how we treat our patients. Part of that is that we have a lot of patients to see. We’re all very busy clinicians. Everyone wants to do their best. But understanding who the highest-risk patient is and what the best evidence is needs to be at the top of your mind as you see your clinic patients, and polyvascular disease resonates. I learned that term from you, Deepak, many years ago. It has been shown in every study to be such a potent marker of risk and beneficial for some of these strategies and other things like diabetes. We need to take that into the clinic and start treating our patients better.

I couldn’t agree more. Hopefully the audience found this exchange of ideas informative, interesting, and educational. Hopefully these are things you can take this into your practices. As I mentioned, I learned a lot. A final point I’ll make is that when you’re thinking about coronary artery disease, think about the whole patient. For that patient you’re seeing for 1 specific condition, that might be the issue in the office for that day. But they may have other risk factors. They may have plaque in other arterial territories. We talked a lot in this session about polyvascular disease, but keep in mind that CAD, PAD, and cerebrovascular disease can coexist. Even though the patient might be seeing you for angina in that office visit or hospital encounter, think about all those associated risks. If you identify those associated risks, you realize that it’s a very high-risk patient, the sort of patient for whom we want to do everything possible to reduce their risk, including intense lifestyle modification. Beyond that, in many cases pharmacotherapy, polypharmacy with wisdom and caution, and in some cases procedural care are all complementary approaches, not competitive approaches.

Thanks to all of you on our panel and to our audience for this rich and informative discussion. If you enjoyed the content, please subscribe to our e-newsletters to receive upcoming 

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A panel of expert cardiologists share their concluding thoughts on management of polyvascular disease in clinical practice.  

Concluding Thoughts

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?

 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.

Those are all good ones. Amy, you’re next. What’s coming down the pike?

 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.

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?

 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.

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

 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.

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.

 I’m checking off everything I can’t say.

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

 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.

Cardiologists share unmet needs and emerging approaches to management of patients with polyvascular disease.

Unmet Needs and Emerging Approaches to Management of Polyvascular Disease

 Well, we've spoken a bit about the COMPASS [Cardiovascular Outcomes for People Using Anticoagulation Strategies] trial, Manesh, maybe you can help us pivot now to talk about the VOYAGER PAD [Vascular Outcomes Study of ASA Along With Rivaroxaban in Endovascular or Surgical Limb Revascularization] trial. This was another trial that looked at the same dual pathway inhibition strategy.

 Thanks, Deepak. And again, I'd say it's been great to work on VOYAGER with Marc and others. And just to remind everyone, we talk a lot about coronary, we think about stents. And in my sort of analogy, actually with VOYAGER now, it gets easier in the periphery. I say that because we don't have a history or an evidence-base, where dual antiplatelet therapy chronically either helps the highway or the pothole. We’ve talked about COMPASS, and I just want to highlight a point you made about COMPASS. I want to be clear. I, like Amy, believe in a sort of scale of justice. When you have all-cause mortality improvement, I don't need to look at the scale that much. And thus, since there are so few therapies, that's why we need a scale of justice because usually there's a risk benefit to everything and there still is with using any therapy including low dose in patients. Once I start to get that level of data I start to go, that's the kind of push I need to move my therapy sometimes from where I am. In PAD, what we said is if we have data in COMPASS that shows chronic vascular improvement, can we do it when you're at the procedure? This was actually what I think, including Marc and others, we've been talking about how approving the procedure is important but what are the downstream events? Not just the cardiovascular events, the limb events.

One thing we've been sort of changing our mind about or at least describing better is acute limb ischemia is an emergency of the lower extremity where you have to go and you have limb loss, amputation, cardiovascular death, MI [myocardial infarction] stroke; these are things that matter. Hence, when you go to the peripheral interventional lab, which we do, and you're using whatever device because you're so focused on trying to get that limb blood flow you spend sometimes 3, 4 hours, and boy, if that patient has to come back in a month, in 6 months, that's really devastating to the patient and to you sometimes. What can you do to prevent long term improvement in that patient so their VOYAGER PAD just roughly 6500 patients randomized too? Again, same thing as COMPASS, aspirin plus whatever else you were going to do versus aspiring plus low dose vascular dose rivaroxaban 2.5 and there was a placebo in the other arm. We’ve looked at all those patients out to 3 years, saw their really high rate of events, and these specific 5 coronary vascular events; cardiovascular MI death, stroke and then limb events, amputation or acute limb ischemia. 19% or so, 3 years, 17% if you got to therapy, sounds like not 2.6 percent absolute risk reduction. 33 patents every 30-so patients, I'm going to reduce 1 of these pretty devastating events. How do I translate that for people? In PAD [peripheral artery disease], whether you're treating the pothole or the highway it works in both. Now, I don't have to be thinking about do I need to do DAPT [dual antiplatelet therapy] …. It's both the pothole when I put a stent in and it's chronically there, so we’ve simplified it a little bit for PAD. Now, you've still got to choose your patient, you’ve got to make sure they're there for the right reasons and do all the other things but that's the way.

That's really good. Sahil, you do a lot of peripheral procedures. How have you integrated, if you have the VOYAGER data into our actual daily practice?

 It comes in 2 phases so I mean most of the patients that I treat are generally chronic patients who we've been caring for and eventually they get to a point where they need something done because they have lifestyle limiting claudication that's refractory to medical therapy. In that patient population, they're sort of more of COMPASS patient. As long as they have not had a recent coronary intervention or acute coronary syndrome [ACS], we are now especially in the higher burden patients moving those patients to dual pathway inhibition in the ambulatory setting. Patients coming in on the other hand either with critical limb ischemia who are the ACS of the legs, if you will that come as quickly as possible to revascularization; those patients upfront we often don't even have time to get the treated medically with adequate therapy but on the flip side after the procedure we're generally sending those patients home with a prescription for dual pathway inhibition.

There are occasional patients, and this is where there's a little bit of gray area where they're on DAPT; let's say it's particularly when I use stents, the platelet as we've talked about already is potentially the bad guy in those patients. With drug eluding stents in the legs as well, there is pretty good evidence that particularly for small caliber along segment of stent therapy, antiplatelet treatment is really important to prevent stent thrombosis in the relatively early phase. Thus, in those patients they wind up getting triple therapy, but we don't think of it in the same way as we do for our Afib [atrial fibrillation] patients where triple therapy is a no-no in so far as possible. Here, they'll get maybe a month of DAPT and then we'll drop to clopidogrel. The study I'd need to see though, is where you drop the aspirin and now, I guess to what we’re doing now with Afib but that’s a conversation for another day.

Usually now, we’re going back to aspirin with low dose rivaroxaban twice daily and I think my threshold for using that in the CLI [claudication/critical limb ischemia] patient is really low. We’ve seen really good response with those patients. In the patients where there’s high bleeding risk, the jury is still out a little bit. We have to sort of titrate to effect and some of those patients certainly early on after their index procedure we'll get them as much antithrombotic therapy as we can and then if they have a bleeding event or if there's concern about bleeding then we'll go back to aspirin monotherapy after a few months’ time. I think those first 6 months are critical in the minimum for even the high bleeding risk patient and if they can manage it, we keep them on maintenance dual pathway inhibition so that's a huge paradigm shift for us.

Yes, that is a big shift. How about in your own practice, Eric?

 I agree, I mean it's interesting. As I was speaking about earlier, we now have, just to Sahil's point, a big population of patients we've been following for some time and we've already put them on rivaroxaban and then they need a procedure. It makes our decision making a lot easier. We bring them in, they're already on their therapy, they get their procedure done and I usually state keep them on the rivaroxaban and aspiring consistent with VOYAGER PAD. After we do the lower extremity procedure and again stenting being a little bit more of a higher risk, we like at least some period of antiplatelet therapy with aspiring and Plavix, but I usually don't give them a refill. In coronary we make sure they have a year's worth if that's their indicated therapy or 6 months’ worth. Here I'll say, “OK, we're going to do 30 days. If clopidogrel runs out, you're staying on your aspirin and use Xarelto 2.5 twice a day” and so that's really, again to Sahil's point, a shift. Again, we needed that kind of encouragement to say, “all right we know COMPASS, but we don't know exactly when we should pull the trigger.” You get these quick visits, or the patient doesn't follow up routinely but now they're in front of us in the procedure lab, it's time to do something different. Let's use that as impetus to make a change. It's going to benefit them short term and long term.

That's interesting to hear that both your practices have been so changed by this trial. It must make you happy to hear that this trial that you led was so influential. Maybe I'll give you, Marc, the final word on VOYAGER and what its implication should be to clinical practice. I mean obviously, it's already changedclinical practice but for our audience, what do you think they should do with these data?

: Well, thank you, Deepak, and great comments. I do think that it was an important trial to do, because as Manesh said, we've extrapolated a lot from coronary trials for a long time in terms of how to treat our PAD patients but we know from trials like CASPAR [Clopidogrel and Acetylsalicylic acid in bypass Surgery for Peripheral Arterial disease] that just applying the same DAPT strategy to peripheral patients actually didn't show any benefit for DAPT. That was bypass not endo but it does show you the heterogeneity that we have to test these strategies in our patients and I think particularly for safety too because there was a lot of concern when we started VOYAGER about periprocedural bleeding and actually it was very modest if any. It told us that physicians are good about knowing when to start antithrombotics. I have a couple of comments – I mean one difference between VOYAGER and COMPASS was that actually you could use clopidogrel in the background and so about half of the VOYAGER patients received DAPT for their primarily endovascular procedures.

Manesh presented the endovascular data as an abstract and what we saw was that it didn't modify the scales of justice at all, that the net benefit for rivaroxaban was completely the same. In fact, the overall absolute benefit versus the absolute risk, it was about a 6 to 1 benefit risk ratio. Clopidogrel had no effect on what rivaroxaban was doing. It really taught us that they're doing different things and that clopidogrel does not modify that sort of thrombin mediated risk. The only thing we saw was that long durations of DAPT as you would expect, led to more bleeding so that the strategy that was talked about, a month or so seemed to be safe but longer durations may lead to more bleeding. I think that also helped to sort of hallucinate a strategy should you want to use a triple therapy approach.

The last thing I'll say about the trial, and we talked about high bleeding risk, but we've seen, I think in a lot of disease states, that we overestimate bleeding risk when it comes to medical therapies and we've seen this a lot in Afib when we're using low doses when we probably shouldn't be or we're not treating people. We've done a bunch of analyses out of COMPASS, out of VOYAGER where we've looked at older patients, frail patients, chronic kidney disease, all these things that make you worry about bleeding, but the scales of justice are the same. There's still a clear net benefit and so I think a lot of the work that went into selecting that low dose to be combined with aspirin has shown consistent net benefit in all of these higher risk populations. That's not to say we disregard bleeding risk and there truly are high bleeding risk patients, but you don't want to turn down a therapy that's beneficial for those patients that could benefit just because you overestimate bleeding risk.

We sort of got burned by that as a community in atrial fibrillation with the fall risk; you might say “oh this person is 80. They might fall. I guess we won't anticoagulate them.” Obviously, those are the patients at highest risk of thromboembolic stroke from Afib so sometimes the fear of doing harm keeps us from doing what's actually in the patient's best interest. This has been a really terrific discussion. I hope the audience enjoyed it about the details of DAPT and dual pathway inhibition and antiplatelet monotherapy so there's a role in the universe for all 3 of these different types of therapies. It's just a matter of identifying the right patient and there's lots of new data to suggest. We went through it rather quickly but hopefully some of what we mentioned will be useful as you're trying to figure out which therapy is best for which patient.

Manesh Patel, MD, reviews VOYAGER trial data and expert cardiologists share where they use DPI [dual pathway inhibition] in their practices. 

VOYAGER Trial and DPI in Clinical Practice

 Marc, you made a good point that I think a lot of people may not have realized about the COMPASS [Cardiovascular Outcomes for People Using Anticoagulation Strategies] trial. Just to recap quickly for the audience, COMPASS was a trial of patients with stable coronary artery disease and, or peripheral artery disease. Generally speaking, at high ischemic risk, but outpatients who were otherwise doing OK on essentially aspirin monotherapy who were then randomized, essentially, again, to continuation of aspirin, or you could say, placebo and rivaroxaban 2.5 BID [twice daily]. There was another arm that I won't discuss, just rivaroxaban monotherapy, but the winner was the combination of dual pathway inhibition aspirin, and the vascular dose of rivaroxaban. But what may not have been evident when the initial publication came out in 

 is that there was actually a mortality benefit. You did mention that, but that's an important point. And actually, those data in greater granularity just came out recently in a secondary publication that Dr [John W.] Eikelboom led in the general American College of Cardiology [ACS], where it lays out the case for how this therapy reduced all-cause mortality. And one can get into specific debates about the statistics, but what's often forgotten is that there was that proceeding trial ATLAS-2, where the same dose—in a slightly different population, post-ACS patients—also reduced all-cause mortality. Thus, these are 2 trials basically showing the same thing in terms of reduction and all-cause mortality. Also, I think there's really something there. What do you think Eric? You've thought a lot about mortality in other situations we talked about.

: It's wonderful to think, we've been talking about thrombotic and we talked about atherothrombosis at the beginning of this session, and you think, “how does this particular therapy address atherothrombosis, and where do we see atherothrombosis?” If you step back and say, “we have this patient with polyvascular disease, why is atherothrombosis such a big risk?” Well, you start in the coronary system when we do a heart attack procedure. Concerning STEMI [ST-elevation myocardial infarction] or NSTEMI [Non-ST-elevation myocardial infarction], we see thrombotic burden. When you put in the stent, we can see thrombosis of the stent. You step back and you say, “OK, well, what other risk does patient have?” Well, we're not great at diagnosing A-fib [atrial fibrillation]. We're getting better with Apple Watches, but silent A-fib leads to stroke. It leads to limb embolization. We talk about DBT [diabetes] and PE [pulmonary embolism] that happens in these patients as well. We know that traditional cardiovascular risk factors actually increase your risk for venous thromboembolism as well; not many people talk about that. And then, you moved on into the legs, where Sahil and I spend most of our Mondays. And when you get into the legs, you can see that people have acute limb ischemia. You've done a fantastic job of teaching people that the equivalent of STEMI is acute limb ischemia. If you have acute limb ischemia, if you have an embolism in your legs, that your risk of saving the leg and saving that patient is on the oral, if not worse than that of a ST-elevation MI [myocardial infarction]. And then, there's also that idea now, and this was from this paper, from the …, and Jack from several years ago that, how do you come from that stable patient with leg pain or claudication into that end stage patient who has critical limb ischemia with ulcers and amputations? And it's probably through thrombosis. It's either occurring from CYT2 thrombosis in those vessels or arterial to arterial embolism, but it's really a thrombotic procedure. Thus, just to summarize that, if we're going to say, all-cause mortality is going to be reduced with an antithrombotic agent, like Xarelto 2.5 BID [twice daily], I just named 5 pathways where that can happen. And I think we see that of our patients with polyvascular disease and anybody, even with individual PAD [peripheral arterial disease], CAD [coronary artery disease] and cerebral vascular disease.

Those were really, really valuable points. And I think by actually treating peripheral artery disease, you get to see just how high-risk those folks are when you're dealing with them in the lab. Amy, what are your thoughts about patients that are particularly high-risk, such as in the COMPASS trial, folks that had diabetes folks that had chronic kidney disease within the COMPASS population, those patients with stable heart failure or examples of patients that had even higher risks of adverse events?

 I think there's that net clinical benefit, as Marc was talking about, when you look at that scale of justice, ways in favor of that net clinical benefit of doing this low dose for rivaroxaban plus that aspirin 81 milligrams a day. And I think, as Eric had pointed out, it's this paradigm shift. It's a little scary at first to start to change your practice so dramatically for all the reasons that we've talked about. We kind of drummed into ourselves that, don't ever stop DAPT [dual antiplatelet therapy] from this time in the 2006-2012 range. And so, this is a big shift in that, but I think that we owe it to our patients to look at the data critically and then to find those patients that really, we think that we can help reduce their risk of future thrombotic events. And I think, as we think about that thrombotic risk versus bleeding risk, if you have a patient who's at high bleeding risk, well, maybe that's not somebody that you're going to apply the COMPASS data too, because that increased bleeding risk that was seen in the low dose rivaroxaban plus aspirin was primarily GI [gastrointestinal]-related bleeding. Thus, if you have somebody who had a history of peptic ulcer disease that hasn't been coalescent or bad diverticulosis, that might not be the right patient to apply it to. However, there's still a huge population of patients who would benefit from this.

Those are really good points that you made. And a number of secondary compass public certainly showed heightened benefit in folks with diabetes, from COMPASS chronic kidney disease, heart failure, with polyvascular disease. Interestingly, even the patients without those things had a benefit, but the absolute benefits were more modest in those subgroups that I mentioned. Hence, certainly, within that COMPASS universe of patients enrolled they are ones that can be identified, where absolute benefits quite large. And you made a valuable point as well about bleeding. When the patients at high bleeding risk, all bets were off, that is intensifying their antithrombotic strategy, whether it's DAPT dual pathway inhibition, almost always backfire. Therefore, you want to use a minimum duration of minimum intensity antithrombotic that you can get away with. Say, if someone had a stent or just had an acute coronary syndrome and try to minimize, that's really important.

Expert cardiologists discuss data from COMPASS trial and the role of rivaroxaban and low-dose aspirin in treatment of patients with CAD and PAD.

Amy Pollak, MD

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