Practical Implications of the COMPASS Trial in Chronic CAD/PAD
JANUARY 15, 2020
Deepak L. Bhatt, MD, MPH: COMPASS is a great study and showed benefit in the overall trial, but also in the 2 major subgroups of coronary artery disease [CAD] patients and peripheral artery disease [PAD] patients, realizing there were a fair number with overlap of the 2, as you pointed out. That happens in real life probably more than we realize. How have those results impacted your own practices? You both deal with a lot of CAD and PAD.
Manesh Patel, MD: I’ll tell you, that’s why smart people like John do these studies. Certainly, if you would have said to me, “We’re going to study 27,000 patients and add a low dose of the factor Xa inhibitor on top of aspirin in chronic pulmonary disease and we’re going to show a benefit,” I would have said, “Boy, that’s a stretch. And not only is it stretch, but gosh, I don’t know if I’m going to do that in my patients.” It’s hard enough to get them to take their aspirin, right?
As a trialist I would have said, “Boy, I don’t know.” And then, this is why we do science, I was shocked at the trial. Not only was it positive, it was so positive that the trial was stopped early, which was a rare thing where the DSMB [Data and Safety Monitoring Board] or the safety board says, “We’re worried that this therapy could help the patients who aren’t getting it, so we’re stopping the trial because there’s a benefit.” That doesn’t happen much.
Then I had to at least think, we should look at it carefully because the safety board says it’s important. And not only was it the myocardial infarction [MI], but the stroke reduction in these patients with atherosclerosis was fairly significant, almost 50%. So that’s something patients tell you about, right?
Vamsi Krishna, MD: We’ve never seen this in any other trial; on top of GDMT [guideline-directed medical therapy], we have not had 40% or more reduction in stroke.
Manesh Patel, MD: Absolutely, on top of the guideline-directed therapy. We spent the first 20, 30 minutes talking about how we can do all the right things, and we all know how hard it is. But in a trial, they’re able to do most of the right stuff, all of it pretty high level, and then got this reduction. So that made me take pause. And then I think the second thing was that I had been, as an interventional cardiologist, a platelet-centric person. I put the stents in, I use 1 antiplatelet drug. If 1 antiplatelet is good, I’ll use 2 drugs to stop the platelets. And if people have more disease, I’m going to use 2 drugs longer. Until they come up with a third one, I’m going to keep using these 2.
So in that era I was a bit shocked to say, “Oh, well, it was a different pathway maybe affecting thrombin directly with anticoagulant, and the dose really matters and getting the right dose might have this effect, and then that translates in mortality.” So if I took myself back to the mid-2010, 2012, 2015 time when these things were going on, I would not have predicted it. It’s affected my practice now as a PAD person in that I see a chronic number of patients with coronary disease who have limb disease, carotid disease. And in those patients, they’ve had multiple interventions. We’re doing anything we can to have to not go back in. I’ve started using more of that therapy because in that patient, I’m thinking
I’m not only going to have a cardiovascular benefit, but in that carotid patient I had referenced earlier, it might have a stroke benefit, and we’ll see as we get into some other ongoing studies about revascularization. But I think in these chronic patients, it’s another thing, especially if there have been a few years out from their MI.
Deepak L. Bhatt, MD, MPH: Who is it that should pull that trigger? You’re seeing in your specialized clinic that patient with PAD or high-risk CAD, and they’ve got a bunch of atherosclerosis and high-risk factors. You were saying that you’ve been influenced by this trial that John led. That’s terrific, but what is the primary physician to do? It is not necessarily so straightforward to identify that patient, is it?
Manesh Patel, MD: I think it is. I guess I would say, I call it—and I think you termed it, you made the term—polyvascular, disease in more than 1 vascular bed. I tell people if it’s in their heart and the limbs, that’s more than 1 vascular bed. That’s a good patient who was in this study, would have gotten a benefit. If it’s in the heart and the carotid, whether we all it peripheral or carotid, that’s more than 1 vascular bed. Now I get a little bit crazy. If it’s in the heart and the kidney, that’s another vascular bed. You may not feel it, but you see creatinine that’s elevated. I’m going to call that polyvascular.
Deepak L. Bhatt, MD, MPH: Well, with Julio Gutierrez, MD, we looked at it in SAVOR-TIMI 53, and we counted that as a vascular bed, even though it’s not strictly speaking renal artery stenosis in that case, but the fact that there is microalbuminuria. That vascular bed is also involved, so I’m glad you said that.
Manesh Patel, MD: Yes, I think the kidney is often crying for attention, if you will. And the only way the kidney finds attention is by occasionally being read on a laboratory test. And so that’s what I have to pay attention to. But I’m sure the nephrologist didn’t like that comment. But in general, I think if you think about the kidney as another microvascular bed, that demonstrates vascular atherosclerosis with abnormal creatinine. Finally, there is heart failure in general, our patients who have multi-vessel disease in more than 1 coronary vessel often. I think about patients who you’d see in your practice. I would start with polyvascular—heart, leg; heart, neck; heart, kidneys—think about those things.
Deepak L. Bhatt, MD, MPH: That’s really very practical and useful and parallels what was actually seen in the trial in terms of groups that can benefit. Can you speak to some of that work that Sonia Anand MD, PhD and other colleagues of yours have done?
John Eikelboom, MBBS, MSc, FRCPC: Certainly. Sonia did a lot work on the risk stratification. Actually, I agree with you, Manesh, in saying it’s actually very simple. Because it’s a bit harder when you’re at the lower end of the risk spectrum to know exactly where you’re at. But for the high-risk patient, it’s a no-brainer, the person with polyvascular disease.
What Sonia found is that people with single vascular bed disease, so just coronary disease, but with the addition of mild to moderate heart failure, with the addition of diabetes, and with the addition of chronic kidney disease—your second vascular bed, Manesh—those people also achieved large absolute benefit. And then if you don’t want to remember any of this, but you just want to count risk factors, we all know that the smoker with hypertension and diabetes, who is dyslipidemic, who doesn’t exercise and has poor diet, and who has got a high BMI [body mass index], they’re at high risk. And none of us have to remember anything.
If you count your risk factors, if you’ve got a half a dozen risk factors, you’re at super high risk, that’s a great treatment for you. This comes back to your cholesterol level and I’d love to hear your thought about that one, but if you’ve got 1 risk factor and your cholesterol is in your boots, and you’ve had 1 vascular event in the past, maybe you’re not the prime candidate for this treatment.
Deepak L. Bhatt, MD, MPH: Since you threw that back at me, I think the tripod analogy you gave is correct. I think even when the LDL [low-density lipoprotein] is really low, there is a benefit in a high-risk patient, where the risk is there. I’m not talking about low-risk primary prevention, but in a patient who is at high risk, where they’ve demonstrated risk with multiple ischemic events and need for multiple revascularization procedures, it’s still good to have antithrombotic therapy onboard as a safety mechanism.
The late Fred Pashkow, MD, actually called it a safety belt. That is, yes, you want to get the LDL and glucose and blood pressure as low as you safely can without adverse effects. But once you’ve done that, there’s still going to be plaque rupture. The absolute risk, as you pointed out before, is much lower. If all those other risk factors are controlled, if the time from ischemic event or revascularization is remote, but it doesn’t go to zero. So assuming that the person’s at low bleeding risk, I think there’s still a potential value there. My feeling is even when the LDL is low, there’s benefit. It’s not just my feeling, datasets show that as well. In fact in COMPASS, even in patients as you know who were very well treated, with all their risk factors, there was still benefit of the 2.5 mg of rivaroxaban. So I think these are, in the right patients who are at high ischemic risk and low bleeding risk, complementary therapies.
Transcript edited for clarity.