COMPASS Trial for CAD and PAD

Deepak Bhatt, MD, MPH: 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 The New England Journal of Medicine 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.

Eric Secemsky, MD: 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.

Deepak Bhatt, MD, MPH: 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?

Amy Pollak, MD: 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.

Deepak Bhatt, MD, MPH: 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.

Transcript Edited for Clarity