Assessing Short-Term Risk in Acute Coronary Syndrome: The Role of P2Y12 Inhibition

  • Roundtable ID: CV38395
    Citation: Published online ahead of print.
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DR. KLEIMAN: You know, it’d be really nice if we actually had a study in which patients were stratified according to bleeding risk, and then P2Y12 inhibitors were selected, probably at random, based on the bleeding risk stratification. 

DR. KIRTANE: I agree. 

DR. KLEIMAN: I think it would generate lots of excitement. 

DR. BRENER: We kind of have that in the PRECISE study,7 at least part of it is retrospective, but we kind of have it.

DR. KLEIMAN: And we all kind of do it, and we all think we’re pretty savvy about it. I think I’m pretty savvy about it, but I may well be wrong. It’d be great to see a study like that. I think people would eat it up.

DR. KIRTANE: Any differences based upon patient risk? Let’s go from unstable angina to non-ST-elevation myocardial infarction (NSTEMI) to ST-elevation myocardial infarction (STEMI) in terms of what agent you use and when. Let’s take STEMI for instance. Tell us what you’re doing with STEMI.

DR. BRENER: We have again an order set, the Pyxis (Becton, Dickinson and Company) in the emergency department—a little bag with aspirin and ticagrelor, 4000 units of heparin, crush ticagrelor, avoid morphine. Lately, I’m trying to avoid fentanyl as well. I thought initially that there is much less inhibition of absorption with fentanyl than there was with morphine, but it turns out that it’s about the same. We crush for everybody, even those who are perfectly fine, and then go to the cath lab.

DR. KIRTANE: Neal, what do you do?

DR. KLEIMAN: Mostly, my concern is to make sure they get something in the emergency room. You know, it’s variable depending on where they’re coming from. I like to see it crushed. I like for it to be ticagrelor. I don’t always get what I want, but as Sorin said, there are many things that we’re doing at once. I just want to make sure they get the right med, I want to make sure they get a P2Y12 antagonist and aspirin quickly, and I want to make sure that they’re triaged appropriately.

DR. KIRTANE: You know, some people have reservations in the STEMI population of loading with a P2Y12 inhibitor. My take on this is that, by and large, patients are almost never going to go for surgery. Also, there is delayed absorption of these agents.8 That’s why, I think, Sorin, you mentioned crushing as a way of overcoming that. But the key thing is that if we don’t give it upstream and early, then it’s really not going to take effect until later. One could use intravenous agents to bridge that, but in general, I think most people have fewer issues giving the P2Y12 inhibitor up front and early in the STEMI cases.

DR. KLEIMAN: There are issues with the opiates that Sorin brought up. The data to me are pretty convincing that they delay drug absorption,8 but on the other hand, patients are in pain. As physicians, we’re supposed to alleviate pain, at least as far as I can remember. The other truth is that if you have elderly patients who you take into the cath lab, you see fewer paradoxical reactions with opiates than benzodiazepines. The last thing you want is to have an unstable patient with an acute myocardial infarction (MI) and also to be struggling to keep the patient calm. I’m well aware of those data, but I’m not sure what to do with them. We have cangrelor on formulary. That’s a recent addition, and I have not used it yet.

DR. BRENER: I use cangrelor in all shock patients, certainly those who are intubated or in any hemodynamic compromise, so we use it in 10% of the MIs, but otherwise not much. 

DR. KIRTANE: Cangrelor is in our protocol as well, and we do use it. I have also seen folks using intravenous glycoprotein IIb/IIIa inhibitors in that situation. The key issue relates to delayed absorption of the oral agents. I think there are ways to overcome this, though. One can crush, and as long as you give it early, and if you use more potent inhibitors, those agents get on board more quickly than, for instance, clopidogrel tablets.

Let’s talk about NSTEMI briefly. What’s your general practice? I know, Sorin, you have order sets, but how do you deal with this? What are patients getting upstream in the cath lab as well?

DR. BRENER: As I said, we do the same thing, because in my mind, the easiest thing to get things done is to have as little variation as possible. You know, I was always a proponent of preloading in NSTEMI. I realize that the data are not there to support that. I accept that. I am not oblivious to the fact that I cannot actually quote a study that really shows that it’s beneficial, but I think it’s not detrimental, and I’m impressed by the fact that people don’t go to the cath lab as early as we would like them to go. 

I think that there is an element of delay which is more common among patients arriving on the weekend who don’t go to cath until Monday, and there’s usually no reason that they should go. I cannot predict up front, and I cannot review every single patient to predict up front who’s going to go right away and who’s not, so I prefer to preload them unless there is an overwhelming reason not to, such as known preexisting surgical disease, where the patient was supposed to come for coronary artery bypass grafting (CABG) and now comes with another ACS. We know that, but otherwise, I just can’t find a reason not to, and for simplicity so that the emergency department always does the same thing, and they don’t have to think about it, it seems to me the right thing to do.

DR. KIRTANE: That makes sense. Let’s transition a little bit to duration of therapy. I know we briefly mentioned it. How long do you continue on these agents? What are you doing with these agents? Is there down-titration, either through dose or different agents? What are you doing after these patients come in?

DR. KLEIMAN: I send them home … actually, all of us here send them home on whatever they were getting in hospital. I think the fewer things you change, the more likely the patient is to be compliant. 

DR. KIRTANE: Sorin, same for you?

DR. BRENER: I couldn’t agree more. I think we have … when I was at the Cleveland Clinic, I used to give people a yellow card that said “if you stop this medication, you will die,” and I was told that that’s not very polite or appropriate, so I’m not using it here, but we try to instill as much this notion that these are important medications. We try to do the same as Neal said, give everything we gave in the hospital on the outside, so a little over 80 percent of people go home on aspirin and ticagrelor after an ACS, with or without revascularization, including surgical revascularization. 

We are cognizant that of the patients who come back—which is at least by my count probably about 60 percent or so—there is a significant amount of switching. So there is probably a down-titration or a downgrading of probably about 25 percent from ticagrelor to clopidogrel for a variety of reasons, such as new oral anticoagulation, preexisting oral anticoagulation, physician preference, patients’ situations, whatever it may be. I think side effects are the least problematic on that list, but occasionally that can happen as well. 

As far as duration of dual antiplatelet therapy (DAPT), I continue beyond one year in people who are at low risk of bleeding and have been asymptomatic and can tolerate the medications, recognizing that the data are soft but not inexistent.9 In the rest, we stop at one year or even earlier if necessary. 

DR. KIRTANE: Yes. We have a similar practice, too. I think that in trying to resolve what a patient is going to go home on and not have to change is really important, so sometimes there is switching that happens, even in the hospital if an insurance can’t cover a specific agent, for example. But most of the time nowadays, we can resolve these issues in-house, and folks will go home on what they were treated with at the hospital. For the higher-risk ACS, that’s typically going to be a potent agent such as ticagrelor. 

The one thing that we’ll typically do in the ACS setting is that we are pretty programmatic about down-titration at a year. For example, if I am going to extend the duration of therapy, I will down-titrate from 90 mg to 60 mg of ticagrelor, which is, I think, a nice facet of that specific agent, with the data from the PEGASUS trial,9 in particular, showing that there’s less bleeding associated with the 60-mg dose, so that’s what we do.

DR. BRENER: We do the same. We actually have it in the electronic medical records, so when you renew the prescription, it asks you whether it’s more than one year or less than one year, and then it automatically alerts you to the need to down-titrate.

DR. KIRTANE: The interesting thing that’s been happening a little bit—I’ve just noticed anecdotally more recently—is that some patients, when they tolerate it, they’re happy to be on it, and they’re a little reluctant to stop it, but they’re more okay stopping aspirin. Absent data, something that I’ve occasionally done is continue them on the P2Y12 inhibitor and drop the aspirin at a year to lower bleeding risk.

As far as the clopidogrel and down-titration of that, we have the same issue that sometimes we do have to do it. The dyspnea component, at least of ticagrelor, should be discussed briefly. I do think that you can treat through it, but from a practical standpoint, for patients it’s sometimes more reassuring to them to just switch, and so I’ve employed both strategies, and it’s definitely something one sees in clinical practice, so you should know how to deal with it. Any other thoughts on that?