DAPT Dilemmas Endure While BMS Should Fade Away


; Wayne B. Batchelor, MD, MHS; Michelle L. O'Donoghue, MD, MPH


November 29, 2017

Robert A. Harrington, MD: Hi. I'm Bob Harrington from Stanford University, and I'm coming to you from the TCT (Transcatheter Cardiovascular Therapeutics) meeting in Denver, Colorado. Today I'm joined by two friends and colleagues. First up is Wayne Batchelor. Wayne is a clinical associate professor of Medicine at Florida State University College of Medicine in Tallahassee, Florida.

Next to Wayne is Michelle O'Donoghue, an assistant professor at Harvard Medical School and an investigator in the TIMI Study Group at Brigham & Women's Hospital in Boston. Thanks for joining us here.

Wayne B. Batchelor, MD, MHS: Thanks.

Michelle L. O'Donoghue, MD, MPH: Thanks, Bob.

Dr Harrington: It's been a fun few days at the TCT—some really interesting trials. Just off camera we were talking about DAPT, dual antiplatelet therapy. Michelle and I got all excited, and Wayne, you said that it's a boring topic. We're going to explore that, in case we need to do any therapy on you to convince you that it's an interesting topic.

Dr Batchelor: I'll let you all describe the study, and we're going to have some input into what is the meaning of all of this and how it translates into changing practice or not.

Dr Harrington: Actually, what I think is going to be interesting is that you, as a really busy interventional cardiologist, have a certain perspective on DAPT. Michelle and I, who participate more in the care of the patient long-term, have a different interpretation—or a different perspective, we'll say. A lot was presented here.

At a late-breaking clinical trial session today, they presented DAPT SENIOR,[1] and DAPT-ST Elevation MI,[2] and there has been one session after another on how to put DAPT in context or how to use the DAPT score. I would say that there's a lot of emotion around the conversation. There's a group that thinks you should go as short as humanly possible with DAPT, and then there's a group that says that there's a lot of bad stuff that continues to happen to people, so let's go longer. The DAPT trial would suggest that longer is better.[3]

DAPT STEMI looked at a group of patients with ST-segment elevation myocardial infarction, heretofore the group that we recommend get 12 months, and boldly randomized them to much shorter durations of DAPT. The second trial, DAPT SENIOR, took a group of patients over the age of 75 (I think the average age was in the low 80s) and randomized them to strategies. They got short-term DAPT, 1 month if they had not had an acute coronary event, 6 months if they had (per guidelines), and once that was determined, they were randomized to bare metal stents or a drug-eluting stent (DES).

Michelle, you're an acute coronary syndromes (ACS) investigator. This almost seems like heresy to go after the 6-12 months, and particularly the 12 months.

Dr O'Donoghue: It's amazing how much this continues to be a source of debate. Wayne and I were talking earlier about the fact that there's such a continental divide. It seems like in Europe people are trying to move toward shorter and shorter durations of DAPT. In the United States we've been moving toward—or holding on, let's say—to longer durations.


Dr O'Donoghue: Let's start with DAPT SENIOR. It's important because we do worry about our patients who are older. In that trial they included some patients who were also on triple therapy, which raises some different questions. Now, for our older patients, all of us are interested in trying to minimize bleeding risk. One thing that is important to emphasize, though, is that DAPT SENIOR did not specifically study shorter versus longer durations of DAPT because the durations were actually similar in the two treatment arms. This was really a study of DES versus BMS in patients over the age of 75.

Dr Harrington: With similar backdrops of DAPT.

Dr O'Donoghue: They happened to incorporate shorter durations of DAPT than we normally would in those populations. It didn't really directly answer that question.

Dr Harrington: Point well taken. That was a lot of the discussion on the panel today—that it was really more of a stenting issue. A lot of us picked BMS in our older patients, who we felt might have a slightly higher risk of bleeding. This basically says, don't do that, that they do get the benefit [from DES] of things like target vessel revascularization reduction without the bleeding burden.

Dr Batchelor: That's helpful to us in the cath lab who are doing these procedures and trying to transfer care to the cardiologist who will be following up in the community afterwards. We can say that if we put in a new-generation, everolimus-eluding DES, the strategy of shortened DAPT is actually very wise.

You still have to put this into context. You still have to look at the patient's inherent risk of bleeding versus thrombosis. I think there's some room for nuance here, whereby if you have a patient who really has a major risk of bleeding, you can probably go short. If you still have a patient who you're really concerned about in terms of residual disease, diffuse disease, etc., perhaps you still have a little room to extend their therapy. Avoiding triple therapy is very important, though. I think we've been shown that through other trials.

The DAPT Score

Dr Harrington: Let's go after something that you're getting at, which is pretty important, and that's the individualizing of antiplatelet therapy. I love the DAPT score and I actually use it. That probably reflects that I'm not as busy as some other people, but I do look it up for individual patients and try to use it as a tool to have a conversation. What do you think about this whole concept, Michelle, of using data about the individual patient to then select short duration versus long?

I caused the bleeding, but nobody knows I prevented the MI.

Dr O'Donoghue: It's the path forward, because when I look at the bulk of the data for longer duration of DAPT versus shorter duration of DAPT, it keeps boiling down to the same thing. As we go longer, it does seem that we have a reduction in stent thrombosis and MI risk, albeit different rates of absolute risk reduction, depending on which patient population you're looking at. But for your ACS patients, by and large, you go longer, you get a reduction in MI. On the flip side, you get an increased risk of bleeding.

We're always going to end up in the same place where we're arguing about which one is more important. Individualization becomes the key because otherwise people are just stuck doing the same thing that they always do, or doing the eyeball test on a patient, which isn't always the best path. I think that clinicians really want tools to help guide their decision-making so tools like the DAPT score make sense.

Dr Batchelor: We're looking at a couple of different things. We're looking at treating atherosclerosis over time in recurrent events. We're looking at treating a stent for stent thrombosis. I think you have to consider what you're treating. Studies like this help me as an interventionalist understand that for stent thrombosis, especially in the first 6-12 months, a shorter period of DAPT therapy is probably fine. In some of those patients who have a higher accrual of events due to their atherosclerotic process over the next 36 months, maybe there is some room for extending the DAPT, as long as their bleeding risk isn't too high.

The challenge with the score is that it's really easy to get to a high score quickly. If you're looking at all STEMI patients, and especially the older patients, you're going to quickly get to a score of 1 or 2, and then you're committing yourself to 30 months, potentially.

Dr Harrington: I heard Gregg Stone talking at this meeting, and he takes things like the scoring system and tries to break it down into the individual patient characteristics—age, gender, diabetes/no diabetes, etc.—but then starts to add the clinical scenario. Was it stable ischemic heart disease or was it ACS? He then adds the angiogram: Is it a high burden of atherosclerotic disease? Is it bifurcation disease? Is it left main disease? One of the most intriguing things from the large DAPT trial[3] was this notion that 40%-plus of the MIs couldn't be attributed to the original stent. They're due to the extra burden of disease. The ability, Michelle, to model all of these data is getting more sophisticated, isn't it?

Dr O'Donoghue: It is, but it remains challenging, as you know. There's always the promise of—we throw these terms around—precision medicine, big data.

Dr Harrington: Machine learning.

Dr O'Donoghue: Exactly. It is still challenging to develop a score that is meaningful and have that validated in additional large datasets.

Dr Harrington: And to have it available at the point of care. It's good to have one of my TIMI friends here because, do you know what was so great about the TIMI risk score? It wasn't that it was so much better than other risk scores in terms of its predictability; what was better is that all you had to do is add up seven things. It was brilliant in its simplicity, as opposed to somebody having a go and typing in a bunch of stuff. For the GRACE Risk Score, you've got to go to your app or to the computer and type in a bunch of stuff. People want simplicity, and we've got to figure out how to give it at the point of care.

Dr O'Donoghue: That's what we're trying to move toward. Just back to the shorter/longer duration question: One thing that we all grapple with our patients is that they always want to pull back on therapy. It's often hard to convince them to go longer, and at the end of the day, they often don't thank you for the MI you've prevented, which they don't see, but they do complain about the bleeding that the drug is causing.

Dr Harrington: A lot of docs will say, "I caused the bleeding, but nobody knows I prevented the MI." That's an uncomfortable feeling.

No Reason for BMS in STEMI

Dr Batchelor: The way that interventionalists look at this versus the follow-up cardiologist in the clinic is a little different. We've had these guttural responses to what we see in the cath lab. We want to do something about the thrombus that we see. We're very polarized. Some of it has to do with the European community versus the US physicians. I also see a bias in interventional cardiologists versus non-interventionalists struggling with this. The interventionalists make decisions on what they see in the cath lab, which may or may not be wrong.

DAPT SENIOR does tells us a couple of things. Number one, event rates are pretty low, and that was helpful. It unfortunately compromised the study's power, but it's reassuring to all of us because both arms did very well on both the bleeding endpoints and the ischemic endpoints.

Dr Harrington: We went quickly through DAPT STEMI, but again, that one suffers from some of the same issues. It's way too small a trial to be definitive. It was noninferiority—way too broad margins to be practice-changing. But, wow, asking a question about DAPT duration in STEMI and being willing to randomize people—that's important.

Dr O'Donoghue: There are patient-selection issues that go into play for both studies—are they representative of the overall population? It's hard to say. With DAPT STEMI, one of my hesitations was that their primary outcome was net clinical outcomes. In a noninferiority trial when you pull in both efficacy and safety with bleeding on one side and MI on the other, and you expect that they're going to go in opposite directions; it becomes harder to interpret. The individual outcomes were relatively underpowered.

Dr Harrington: That was the exact comment I made on the discussion panel today, which is that combining the safety and efficacy endpoints in a noninferiority trial makes this really tricky. If you think back to the original trials and REPLACE-2[4] with bivalirudin, we did it very differently. We called for noninferiority on the ischemic endpoints and superiority on the bleeding endpoints. We called them out purposefully for the reason that you said: because it makes interpretation tricky.

Dr Batchelor: One of the other take-home messages is that there's really not a good reason to be putting in BMS anymore in STEMIs. It's very clear. We've got meta-analytical data in lower-risk patients and now we have these data. It's just volumes of data. I just don't see any value [for BMS over DES]. And this study helped move that along a little in terms of shortening the DAPT, being safe, and using everolimus-eluting stents, and that works very well.

Dr Harrington: As we come to the end of our time, are you more excited about DAPT now than you were at the beginning of the conversation?

Dr Batchelor: Marginally. No—yes, definitely.

Dr Harrington: We'll still work on you. But it's a lot of discussion, a lot to be learned. Probably neither of these trials is practice-changing but they're trials that really do set hypotheses to go forward—is that fair?

Dr Batchelor: A good summary.

Dr O'Donoghue: I agree with Wayne's point that it really does, in my mind, solidify the idea that we should be moving away from BMS. I think that's one of the main takeaways.

Dr Harrington: Individualizing our DAPT selections.

Dr Batchelor: Yes.

Dr Harrington: Great. Wayne, Michelle, thanks for joining us here on Medscape Cardiology, and thanks to you, the listener.


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