DR. KIRTANE: It’s great to have both Sorin J. Brener, from New York Presbyterian Brooklyn Methodist Hospital, and Neal S. Kleiman, from Houston Methodist DeBakey Heart and Vascular Center, The Houston Methodist Hospital, here today, and let’s just launch right into it. Maybe we’ll start just generically, and either of you can jump in. Tell me a little bit about what you worry most about in terms of patients with acute coronary syndrome (ACS) when they come to the hospital, with respect to both potential recurrent ischemia and bleeding, and what strategies might you use to mitigate some of those risks.
DR. BRENER: Maybe I’ll start. I think there are three levels of concern. The first is that we provide systematic guideline-directed therapy to patients with bona fide ACS,1 and I think it’s important to make sure that they really have the disease we’re aiming at. That’s number one. Number two is that they receive the therapy in a timely fashion, and number three is—because the length of hospitalization is so short these days—that we have in place immediately upon admission the mechanisms that are needed to ensure smooth transition to home, which means the right medications, appointments for follow-up and cardiac rehab, and so on. That’s why I think we need to attack all of those right upon admission, because it’s not going to be a long one.
DR. KLEIMAN: Yes, Sorin. I think you’ve hit on some of the really critical points. Number one, we’ve got to make sure we have the correct diagnosis. We’ve all been asked to see lots of patients for ACS who are started on a variety of meds that carry some benefit in the right patients and some risks in both the right and wrong patients. We all see that often patients who don’t have the syndrome end up receiving medication and assume all the risks without the benefit, so number one is you’ve got to make sure you’re treating the right patient group.
Number two, as Sorin said, is to make sure that the transition home is smooth, that medications are given properly, that instructions are given properly, that medications aren’t interrupted, and that patients understand what they have and what they’ve got to do about it.
DR. KIRTANE: I think those are great overall summaries, and maybe we’ll go directly into the specifics of when patients show up in the hospital, because it’s important to sort of take a step back and address what we’re trying to do globally and then, perhaps, focus on specific therapies themselves. Maybe we can start with prevention of ischemic events. We do know that patients are coming in with ACS, or even percutaneous coronary intervention (PCI)—which in some respects is an iatrogenic ACS, where you’re causing plaque rupture by blowing up a balloon. I think that people have been sort of going away from the thought that we need some antiplatelet protection during both those events, ACS as well as PCI.
If you look at the rates, for instance, of preloading that occur in the United States, they are quite low, even though guidelines recommend preloading with antiplatelet agents (eg, P2Y12 inhibitors) prior to PCI in ACS patients.1 Even for elective PCI, there are many patients who come into the cath lab and are only getting loaded with antiplatelet agents such as P2Y12 inhibitors on the table or afterward. Why do you think that is? Is that what you both do in your practices? Maybe talk us through both those scenarios.
DR. KLEIMAN: I think, truthfully, many of the patients who aren’t preloaded are not preloaded because someone has overlooked it. I think in some institutions, there is surgical concern about the likelihood of finding surgical disease and the need to delay things if that’s the case. I don’t really think that’s the case in most institutions. I think frequently it’s because we don’t think of things because we’re not focused on the things we ought to be focused on.
DR. KIRTANE: Sorin, what do you think, and what do you actually do?
DR. BRENER: Doing and thinking are different, because doing is depending on who does what. In New York, it’s more open and everybody has opinions, and they act on them. In general, I think this is a case where the logic seems to be at odds with the data, so it would make perfect sense that preloading patients before PCI with or without ACS would be beneficial.
It’s just that we haven’t been able to muster the data, and I think that since the CREDO2 days, which is almost two decades ago, and the CURE3 days, which is two decades ago, we really haven’t been able to generate good data to support it. That’s the reason that I think you’re right; there is a decline in the rate of preloading prior to arrival to the cath lab, which I think is unfortunate in the case of ACS. It may be a little less so in the case of stable coronary disease.
That being said, part of it has to do with the fact that the technique and technology have improved so much that for the practicing physician, there may be years elapsing between bad outcomes that are directly related to the lack of platelet inhibition at the time of PCI. I think that the memory is just not sufficiently strong for that. That’s why I’m a big proponent of guidelines and of order sets. I use them extensively, and I don’t allow people to get on the cardiac catheterization table without those order sets being followed appropriately, certainly for ACS patients.
DR. KIRTANE: I think it’s very interesting. Back in the days of the IIb/IIIa inhibitors, there was such a heavy focus on platelet inhibition at the time of the PCI, and perhaps even ACS. But then with some of the negative trial data with the upstream use of IIb/IIIa inhibition, and even more focus on bleeding and the surgical issue that Neal rightly mentioned, I don’t think there’s as great an emphasis in the present day on platelet inhibition at the time of PCI and even ACS.
DR. KLEIMAN: I mean, look, the real truth is that it hasn’t diminished in importance one iota, but it’s no longer the topic that generates the most excitement at our meetings. That doesn’t make it less important, but it makes it a little less prominent. It really should be second nature, but we all like to say that we’re forward-looking and like to think about newer, more exciting technology, but this stuff’s awfully important. Sometimes that’s not easy to remember.
DR. KIRTANE: That’s a great point. Let’s focus a little bit upon what can be done after ACS. What are you doing at your institutions with P2Y12 inhibitors? Virtually everyone is getting aspirin. Typically, people are getting loaded with 325 mg. It is important in light of some of the data in the last year to recognize that aspirin for people who actually have true coronary disease (eg, ACS, PCI, and secondary prevention scenarios) does have real benefits.4 But for P2Y12 inhibition, what are you giving, when are you giving it—before, during, and after PCI?
DR. BRENER: I think you are referring to the patients with ACS or to those with stable coronary disease?
DR. KIRTANE: ACS predominantly.
DR. BRENER: So, as I said, we’re using order sets that are very specific. All patients get aspirin and ticagrelor upon admission without room for consideration. The physician has the option to click a box where they say that they prefer to give clopidogrel rather than ticagrelor, and then they have to put a reason, so it can’t be left blank. It hasn’t happened in the last few years. I monitor all of those, so it just doesn’t happen. That’s at the front end, I would say, very close to 100 percent compliance with that part.
At hospital discharge, obviously some patients are switched to clopidogrel if they are on an anticoagulant, on either warfarin or a direct thrombin or factor X inhibitor with various permutations of dual or triple therapy. A small proportion are switched from ticagrelor to clopidogrel either because of terrible side effects or because of financial issues, but I would say that about 80 plus percent of people leave the hospital on aspirin and ticagrelor, at least for the first month pretty consistently.
DR. KIRTANE: Neal, what do you do?
DR. KLEIMAN: We’ve got a mix that’s closer to 50/50. Large institution, State of Texas, people are very independent-minded, so getting agreement to use an order set is more difficult than it is in many institutions—but it’d be very nice if we could. I think we’d see a lot more ticagrelor use. We don’t see as much as we should in the emergency room either, and I think that’s got a little bit to do with built-in institutional complexities of getting the stuff ordered and getting it through pharmacy.
DR. KIRTANE: Yes. At least in our institution, we tend to favor for ACS the more potent agents, either ticagrelor or prasugrel. I do think that because of the ACCOAST data,5 we are not preloading with prasugrel, and so that agent would only be used post-PCI. Thus, in a lot of cases, other agents may be favored, at least in our institution.
As far as the preloading issue goes, we have a somewhat unique protocol in the sense that if there’s a long delay to getting to the cath lab—for instance, the patient comes in Friday night and is stable—those patients will often get preloaded with a P2Y12 inhibitor, but if the patients are going to the cath lab rapidly, we often don’t preload, and we’ll use more intensive platelet inhibition such as cangrelor at the time of PCI and then transition them to ticagrelor simply because that’s an easier transition because of the lack of drug–drug interactions at the level of P2Y12 receptor. I will say, though, that there are scenarios where we won’t use more potent agents. Those are patients perhaps at the highest risk of bleeding or other issues such as those, but by and large, we try to use more potent agents just because of data such as those from PLATO.6
For elective PCI, I think the jury is a little bit out, but we do—even for our elective PCIs—preload typically with clopidogrel two hours prior to the PCI unless the stress test is super high-risk or there’s valvular disease that we’re worried about.
It is interesting—among the three of us, while there are some differences, there are many similarities, because I think the three of us are attuned to the fact that we want platelet inhibition as prevention of ischemic events.