DR. FERDINAND: This is the second part of a two-part roundtable discussion series on the updated American College of Cardiology Foundation/American Heart Association (ACCF/AHA) guidelines on the management of ST-segment-elevation myocardial infarction (STEMI).1 We’re going to focus mainly on the implications for antiplatelet therapy. As you know, acute coronary syndromes (ACS) encompass a constellation of symptoms, including those related to unstable angina and non-ST-segment-elevation myocardial infarction (NSTEMI). For the purposes of this roundtable we’re going to be discussing specifically STEMI.
I’m Keith C. Ferdinand, MD. I’m a professor of clinical medicine at the Tulane University School of Medicine in New Orleans, Louisiana.
DR. LAVIE: This is Carl “Chip” Lavie. I’m a medical director of cardiac rehabilitation and preventive cardiology and director of the exercise laboratories at the John Ochsner Heart and Vascular Institute, Ochsner Clinical School, the University of Queensland School of Medicine in New Orleans, Louisiana.
DR. FOODY: This is JoAnne M. Foody, MD. I’m an associate professor at Harvard Medical School and I’m director of the cardiovascular wellness center at Brigham and Women’s Hospital in Boston, Massachusetts.
DR. BERGER: I’m Jeffrey Berger. I’m an assistant professor of medicine and surgery at NYU School of Medicine and director of cardiovascular thrombosis.
DR. FERDINAND: In STEMI, the infarct artery is almost always completely occluded and the patients have more severe symptoms than they do with NSTEMI in which the artery is only partially occluded. Unstable angina and NSTEMI have certain clinical presentations, but with STEMI the complete occlusion means that it’s urgent that the artery is recanalized as soon as possible and direct coronary intervention is considered the appropriate care.
Specifically as it relates to antiplatelet therapy, dual antiplatelet therapy both during and after reperfusion is recommended. We have, along with clopidogrel, newly available P2Y12 inhibitors for patients undergoing primary percutaneous intervention. Only clopidogrel and prasugrel are recommended after fibrinolytic therapy and we will discuss why that may be—why ticagrelor is not indicated in that particular situation, whether it’s something nuanced related to the drug itself or just to the clinical evidence on which the recommendations are based.
Let’s go with some questions. The first one is similar to what we had when we discussed unstable angina and NSTEMI. What’s the most significant change you see in the updated guidelines?
DR. LAVIE: Well, I think the most significant change is similar to what we discussed in the NSTEMI guidelines, which is the addition of ticagrelor, the newest oral antiplatelet agent that is indicated for the treatment of patients with STEMI, NSTEMI, as well as unstable angina, regardless of whether the patient is managed medically or with intervention/revascularization. If there’s not the availability of care and immediate percutaneous intervention then they obviously need thrombolytic therapy, and at present, these patients would probably not get ticagrelor.
The reason is two-fold. One is that it was an exclusion criterion in the Platelet Inhibition and Patient Outcomes (PLATO) trial (no fibrinolytic therapy within 24 hours of randomization), which was probably due to concern that ticagrelor was more potent and that combining such a potent antiplatelet agent with fibrinolytic therapy might increase the risk of bleeding.
I think the initial thought was that ticagrelor was going to be associated with a lot more major bleeding compared to clopidogrel, and it was associated with a little bit more major bleeding, at least in those who were not managed with bypass.2 There still was not very much difference between clopidogrel and ticagrelor, so maybe if they were doing the trial over again, maybe they would have allowed the thrombolytic therapy, but I think that right now since it was not used in the PLATO trial, the fact that it is a lot more potent and is at least associated with a modest increase in major bleeding (at least in those who did not receive bypass surgery), we probably should only use ticagrelor in the STEMI patient who is treated with percutaneous intervention.
DR. FERDINAND: Dr. Berger, do you agree that the guidelines seem to tease out this idea that with thrombolytic therapy ticagrelor should not be utilized, and it’s not even listed as an alternative.
DR. FOODY: I’m sorry, just one more comment though, to clarify. The guidelines are very specific that with fibrinolytic therapy, only clopidogrel is recommended. Prasugrel can be used in the setting of percutaneous coronary intervention (PCI) following fibrinolytic therapy. There’s a little bit of a nuance there.
DR. FERDINAND: Why don’t you say it again, Dr. Foody? State it very clearly for the recording. What’s the difference?
DR. FOODY: When using fibrinolytic therapy only, the only drug that’s been studied in that setting is clopidogrel in conjunction with aspirin and heparin. In individuals who go on to PCI after fibrinolytic therapy, either for bailout or recurrent symptoms, both clopidogrel and prasugrel have been studied. In those hospitals where fibrinolytic therapy may be the primary reperfusion strategy, those individuals should be using per these guidelines, clopidogrel as their dual antiplatelet of choice.
DR. BERGER: Right. I think that is an excellent point. I think there were very few patients in the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel Thrombolysis in Myocardial Infarction 38 (TRITON-TIMI 38) who actually had previous fibrinolytic therapy before they underwent their PCI and STEMI. I think that in a patient who received thrombolytic therapy for reperfusion therapy, I would use aspirin and clopidogrel being my second antiplatelet drug. I would not use one of the more potent drugs for fear of just increasing the risk of bleeding too much.
DR. FERDINAND: Now, you’re in New York City. I visited Manhattan many times and I am always impressed with how many people they have packed in such a small area. Do you ever have a person that needs to have fibrinolytic therapy vs direct PCI?
DR. BERGER: We do. I round in the coronary care unit at Bellevue Hospital. It is the flagship hospital of the New York City Health and Hospitals Corporation, which is a composite of many hospitals surrounding the city. We get a lot of patients who come in with a STEMI at one of these local hospitals. Depending upon how long it would take for them to be transferred to our hospital, many of them will get pharmacologic reperfusion if it will just take too long to transfer and we would not have a fast enough door-to-balloon time. So I actually see a handful of patients who undergo thrombolytic therapy for one reason or another.
DR. FERDINAND: I’m really surprised because you’re talking about an island that’s only 26 miles and it has hospitals, it seems to me, every ten blocks. That does happen?
DR. BERGER: Yes, it definitely happens. In fact, the population of patients we see is quite amazing. For one reason or another, patients could delay coming into the hospital hours or days following their symptom onset.
DR. FERDINAND: So some of it may be what we call health illiteracy and some of it may be patient preference. There are a lot of cultural barriers, especially in new immigrants and some ethnic minorities in terms of going to the hospital. That’s the last thing you do, go to the hospital, so they may have delayed their presentation for almost a day.
DR. BERGER: Right.
DR. FERDINAND: Now, one of the things that I did notice in the new guidelines, they are a little sensitive about the aspirin dosage. We had talked about this in the unstable angina section, but even with primary PCI there’s still a question of whether or not 81 mg is the preferred dose. They give it a Class IIa level of evidence B, suggesting that you don’t have to use the 81 mg. Why do you think they nuanced that a little bit?
DR. BERGER: Right. I think this is very, very important. I think it’s important to actually mention there’s a randomized trial called CURRENT-OASIS 7 which randomized patients with an ACS to low- or high-dose aspirin after their initial dose. Every patient got a loading dose of aspirin and then they got 30 days of either 81 mg vs 325 mg. As we all know, there was no added benefit for aspirin 325 mg vs 81 mg.3 Moreover, there was no benefit of using the higher aspirin dose even in those patients who underwent PCI. There was, however, significantly more minor bleeding, which was not so minor—it was gastrointestinal bleeding—in the group that got 325 mg.3 I think because of that trial, that’s why the guidelines came out and gave a stronger recommendation for aspirin 81 mg than we have seen previously.
DR. LAVIE: I do not think there are that many trials in ACS and STEMI that have used 81 mg of aspirin. Most of the stent trials and the percutaneous transluminal coronary angioplasty (PTCA) trials for 20 years have used 325 mg aspirin in the United States. Not that 325 mg aspirin was shown to be better than 81 mg, nevertheless, it was just the standard dose used in all the initial stent trials.
So US cardiologists, and in particular US interventional cardiologists, have primarily used 325 mg of aspirin. This explains why for the PLATO trial, you see that in the whole trial, which was almost 90% from non-North American and non-United States, these patients generally were treated with less than 100 mg of aspirin. However, in North America and the United States, it was something like 54% of patients who received doses above 300 mg of aspirin.4
I think that right now there is recognition that many patients are still getting 325 mg of aspirin in the United States. There are probably very little data, with the OASIS trial being one that shows the efficacy of 81 mg, but there are very little data on 81 mg and a lot more data, particularly the older data, where patients were treated with 325 mg of aspirin.