ACC/AHA STEMI Guidelines: Judging Time and Choosing Reperfusion Methods (08/2005)

DOLPH HUTTER, MD: Hello. I’m Dolph Hutter. Welcome to the American College of Cardiology Conversations with the Experts. In this program, we will discuss ACC/AHA STEMI guidelines and more specifically the need to judge time and setting when choosing reperfusion methods. Joining me to discuss this topic via telephone is Dr. Deepak Bhatt, an Interventional Cardiologist at the Cleveland Clinic Foundation and Dr. Sidney Smith, Professor of Medicine and Director of the Center for Cardiovascular Sciences and Medicine at the University of North Carolina, at Chapel Hill.

Thank you both for joining me. This is obviously a very important topic, and people have to make fast decisions. Sid, what are the guidelines? How do you decide between fibrinolytic therapy and PCI, and how does time enter into it?

SIDNEY SMITH, MD: Well, I think if we look at the new guidelines, the really important message is that primary PCI, if it can be performed in the appropriate environment with the right timing, is the preferred approach for most patients.

This is based on the Keeley-Grines analysis that came out in Lancet in 2003 in 23 randomized clinical trials showing favorable outcomes for PTCA versus fibrinolysis.

Now, the new guidelines contain...

DOLPH HUTTER, MD: Let me just stop you there. So if you’re in a center where you’ve got the PCI lab right there, that’s a pretty clear-cut decision. Is that what you’re saying?

SIDNEY SMITH, MD: It’s a clear-cut decision if you have door-to-balloon times in the range of 90 minutes and if you have experienced personnel and if you have onsite surgery or you have an established plan to transfer to onsite surgery. So there are criteria for doing PCI which are very important.

DOLPH HUTTER, MD: Okay. Now, Deepak, do you agree with that? I mean, that’s at least a subset that’s pretty clear-cut.

DEEPAK L. BHATT, MD: Yes. I think this new set of guidelines, which Sid, of course, was part of writing, are really terrific inasmuch as it gives lots of practical advice on how to triage patients for lytic versus primary PCI, with some real advice about time to treatment, which has always been a little bit of a difficult point, I think, for practitioners to know, when should you pull the trigger, say to transfer for primary PCI? When should you just go ahead and lyse? So I think this set of guidelines is really helpful to clinicians in that respect.

DOLPH HUTTER, MD: All right. Now, Sid, are you talking about door-to-balloon time or symptom-to-balloon time?

SIDNEY SMITH, MD: Well, the new guidelines are talking about door-to-balloon time and door-to-needle time.

DOLPH HUTTER, MD: Okay, good. That makes it easy, doesn’t it?

SIDNEY SMITH, MD: Yes. Although there are people that would argue that symptoms to balloon would be a little bit better.

DOLPH HUTTER, MD: Oh, yes. I understand. But at least we’ve got to go with what the guidelines say.

SIDNEY SMITH, MD: Exactly.

DOLPH HUTTER, MD: What are some of the other caveats from these guidelines?

SIDNEY SMITH, MD: Well, you know, some of the things that have been observed, certainly, with thrombolytic therapy, that the higher risk group that you’re treating, the more likely you are to see a benefit from PCI. And especially patients in shock, patients in failure. So in that group of patients, you’re more likely to see a benefit from PCI.

On the other hand, there are some fairly compelling data to suggest that patients who arrive within two to three hours, very early on, where your labs may be full, let’s say you want to do a PCI, but you can’t get them there promptly for one reason or another, fibrinolysis is not a bad way to go early on, within two to three hours.

DOLPH HUTTER, MD: And of course, that can also be in the community hospital, where it might take more than 90 minutes to get them to balloon time, in that setting fibrinolysis might be the way to go.

SIDNEY SMITH, MD: That’s right.

DOLPH HUTTER, MD: Deepak, do you agree with that? What kind of a time setting would you use?

DEEPAK L. BHATT, MD: Yes, I would agree with all those points Sid made. I think especially if shock or near shock-like states are present, you’ve really got to more strongly consider PCI over lysis.

DEEPAK L. BHATT, MD: And when it’s outright shock, I think that everyone would agree on that. But a lot of times, even if the patient’s just starting to show some hemodynamic instability and it’s an anterior MI, I think really that would push me, assuming that it could be done within an appropriate time frame to go towards PCI over lysis.

The other sort of issue, beyond just ischemic risk, that is a large territory at risk, as would be the case with cardiogenic shock, would also be bleeding risk. That is, if a patient I perceive is at high risk of intracranial hemorrhage, there again I think is something that would push me away from lysis but towards primary PCI.

DOLPH HUTTER, MD: And Sid, that’s what the guidelines say, also, isn’t that right?

SIDNEY SMITH, MD: That’s right. But, you know, the other area you get into is this whole emerging area of prehospital fibrinolysis, where you see reduction in treatment delay up to an hour and reductions in mortality.

DOLPH HUTTER, MD: Let me come back to that. I want to stay on the simple things first, because I’ve got tougher questions for you guys later on.

Your in the community hospital and its more than 2 hours to a PCI institution. What do you do? [Do you use] thrombolysis alone and keep the patient there? Do you go with thrombolysis and transfer the patient in? What do you think? What do the guidelines say?

SIDNEY SMITH, MD: Well, you’re at an outlying hospital, and you are two hours into the infarct and you can give fibrinolysis in a patient that does not have congestive failure, does not have any problems, and no contraindication to fibrinolysis. Then you have to weigh what is the time to ship to your next center? Are they able to get into the cath lab? If you’re looking at an hour to transfer and another hour and a half to get in for a PCI, you may be better off staying there and going ahead with fibrinolysis.

DOLPH HUTTER, MD: Yes. Well, that’s exactly the situation I’m trying to establish. Your at a community hospital, you can’t make that 90-minute window, you have no complications. You can make a good argument for fibrinolysis alone. Is that fair?

DEEPAK L. BHATT, MD: Yes, I think that’s a reasonable option, though I would still vote to transfer that patient after they got their lytic so they can do PCI.

SIDNEY SMITH, MD: Absolutely.

DOLPH HUTTER, MD: Yes. And I think we would all agree with that. You can never know if the patient’s going to become unstable.

SIDNEY SMITH, MD: I would agree with that. I think that Deepak is exactly right. And when you look at trials, like the DANAMI trial comparing shipping to giving fibrinolysis, the major difference in the two groups was the group that got fibrinolysis stayed at the hospital and did not have an option for reperfusion with PCI.

DOLPH HUTTER, MD: Yes.

SIDNEY SMITH, MD: So I think that if you were to have shipped those patients and opened the option for PCI, it might have been a pretty, pretty close endpoint for the two groups.

DOLPH HUTTER, MD: Yes, and you know, I think that’s just a very good argument conceptually. Why not get them to a place so that if something occurs, either a recurrent ischemia occurs or infarct extension, you can go right to the cath lab?

SIDNEY SMITH, MD: Right.

DOLPH HUTTER, MD: Now, this leads us to another question, what about facilitated PCI? You know you start fibrinolysis on the way to the cath lab either in your institution or another institution. Sid, do you want to comment on that, and then Deepak?

SIDNEY SMITH, MD: Well, you’ve got two groups. You have prehospital lysis. That is lysis initiated in the field, and you’ve got CAPTIM, which shows very favorable outcomes for prehospital lysis that’s initiated in less than two hours. Actually, none of the patients going into shock. After two hours, PCI looking better. So very, very early prehospital lysis in CAPTIM looking pretty good.

DOLPH HUTTER, MD: Was that full-dose lysis?

SIDNEY SMITH, MD: Yes.

DOLPH HUTTER, MD: Okay, all right.

SIDNEY SMITH, MD: However, facilitated PCI, which happens to be a concept that appeals to me, get to them in the field, give a modified dose of fibrinolysis, got a 2B recommendation in the guidelines, and interestingly, ASSENT-4 has been stopped early. It was actually a surprise to me. So I think we have a lot more to learn.

DOLPH HUTTER, MD: Stopped early because of what? Why was it stopped early?

SIDNEY SMITH, MD: There was poorer outcomes in the group undergoing PCI. And Deepak, you may have some information on it. Were you involved in ASSENT-4?

DEEPAK L. BHATT, MD: I wasn’t involved with ASSENT-4, but interestingly, as you mentioned, Sid, that trial was stopped prematurely. Actually, I should say the DSMB apparently recommended to the steering committee to stop it. And it wasn’t just that there was increased bleeding. In fact, that’s what one might have anticipated, more intracranial hemorrhage or something like that. But in fact, the so-called facilitated arm, that is getting lytic and going on to PCI, actually had a higher rate of ischemic events. So we don’t have the final data, but at least this is what’s been out there. And that really makes me a little bit nervous about facilitated PCI, if by facilitation we mean giving some dose of lytic and then routinely proceeding to the catheterization laboratory for PCI.

DOLPH HUTTER, MD: So you’re both expressing caution about using a partial lytic dose, and then routinely going to PCI. Is that fair?

SIDNEY SMITH, MD: That’s very fair.

DOLPH HUTTER, MD: Okay.

SIDNEY SMITH, MD: The fascinating thing is, it’s sort of shades of what we were seeing earlier in the fibrinolytic area was just balloon angioplasty with a higher complication rate.

DOLPH HUTTER, MD: Well, that’s a pretty good negative point. Maybe that’s not the thing to do at this time. So either start fibrinolysis and get into a hospital where PCI could be done if indicated, depending on the situation, or send them directly to a facility for PCI if you can get there within a balloon time of 90 minutes. That’s pretty clear-cut, then?

SIDNEY SMITH, MD: Yes.

DEEPAK L. BHATT, MD: Yes, I like that algorithm. You know, lytics, of course, can induce platelet activation and of course activated platelets and PCI don’t necessarily mix well.

DOLPH HUTTER, MD: That’s right.

DEEPAK L. BHATT, MD: So maybe that’s why ASSENT-4 gave us those surprising results.

DOLPH HUTTER, MD: Well, that’s a very good cautionary point about facilitative PCI. Now what about the sick patient? The patient is three hours into the infarct, but they have either cardiogenic shock or hypotension with heart failure. Isn’t the time frame longer for that patient, to get them in for a PCI?

SIDNEY SMITH, MD: Yes.

DOLPH HUTTER, MD: In terms of hours?

SIDNEY SMITH, MD: Well, I don’t know. I think you still want to get there as quickly as you can.

DOLPH HUTTER, MD: Yes.

SIDNEY SMITH, MD: But I think that we really need to look at our systems of care, because the EMT needs to make a decision about whether or not to get to an emergency room, or maybe it’s another 20 minutes to get to a facility where they would have a cath lab and can put a balloon in.

DOLPH HUTTER, MD: And of course, that could be made with physician input by radiophone.

DEEPAK L. BHATT, MD: I think so.

DOLPH HUTTER, MD: Yes. I guess my point I’m trying to get at, do you think if it’s six hours in the MI and they’re hemodynamically unstable, that’s not too late to open the artery, is it?

DEEPAK L. BHATT, MD: No. No, I think really there’s a circumstance where you want to get a patient to a cath lab as quickly as possible and go ahead and open up the artery. You know, certainly, the SHOCK data support the value of PCI in patients with cardiogenic shock. I think the problem, really, with a shock patient is, quite obviously, many times they’re very ill, and that can sometimes create this sort of reluctance in the system to proceed with PCI, despite the fact that the data supports that.

DOLPH HUTTER, MD: By the way, the SHOCK Trial, what was the time frame for benefit in the SHOCK trial that was published by Judith Hochman? Was it eighteen hours?

SIDNEY SMITH, MD: 36 hours after the onset of symptoms.

DEEPAK L. BHATT, MD: Yes. The window is much longer than, I think, many clinicians appreciate.

DOLPH HUTTER, MD: Okay, I guess what we’re saying, if its going to be longer than 90 minutes to PCI and there are no contraindications to thrombolysis, thrombolysis is the way to go, but if you can get to the balloon in 90 minutes PCI wins. And clearly, if you’re at an institution with experienced people in the lab, there PCI definitely wins, Is that a fair summary?

DEEPAK L. BHATT, MD: It is. You know, in fairness, in real life, that 90 minutes is hard to achieve. That is, lots of hospitals are shooting for that, but it is a bit easier said than done. A lot of practical impediments. But I think as these guidelines are more widely promulgated, it’s a target that we’re all shooting for, shooting to hit and even surpass.

SIDNEY SMITH, MD: Hey Dolph, let me just clear up that the SHOCK recommendations are within 18 hours of the onset of shock. 36 hours for symptoms.

DOLPH HUTTER, MD: Right. 18 hours for shock. That’s the number I was thinking of, but 36 hours from the onset of symptoms, very important point. Thank you for clarifying that Sid.

SIDNEY SMITH, MD: Okay.

DOLPH HUTTER, MD: Okay, guys. That’s very helpful, and particularly the negative point about facilitated PCI. That’s not quite ready for prime time use yet.

DEEPAK L. BHATT, MD: I guess it also depends on what’s meant by facilitation. A lot of different people use it differently. For the lytic part, I think we really ought to wait, especially given ASSENT-4 and the neutral, if not negative, findings there. But there is an ongoing facilitated PCI trial, FINESSE, that’s a little over halfway through, and perhaps we’ll have more data regarding what to do in terms of facilitation with lytic, with IIb/IIIa inhibitors, which were another part of the potential facilitation strategy. And the other thing to throw out there, too, in terms of facilitation would be oral antiplatelet agents. Of course, everyone will get aspirin, but perhaps higher loading doses of clopidogrel.

DOLPH HUTTER, MD: That’s right. And of course, then, you get into clopidogrel and you find out that you need emergency surgery, that’s a topic for another time. But I think the common thing is that this scene is changing yearly and we all better stay tuned.

SIDNEY SMITH, MD: Absolutely. And I think look for more discussion about how centers can work together in a system.

DOLPH HUTTER, MD: Yes. Good point.

DEEPAK L. BHATT, MD: You know, Sid mentioned the DANAMI study, and it’s really quite remarkable. I had the opportunity to host some physicians from Denmark a couple of years ago, and they’ve really got an excellent system of health care in terms of delivering facilitated PCI or primary PCI, or just care in general to the patient with STEMI.

DOLPH HUTTER, MD: Well you both make a good point. You know, develop those relationships between outside hospitals and PCI hospitals before the fact so that the machinery is well oiled when the event occurs.

SIDNEY SMITH, MD: Yes. The door-to-balloon times in DANAMI were 93 minutes. Similar in PRAGUE-2. So the systems are important.

DEEPAK L. BHATT, MD: Of course, those are smaller countries and, you know, more homogeneous health care systems, but I think there’s a lot we could learn from them.

DOLPH HUTTER, MD: So to briefly summarize, you should consider primary PCI when door to balloon times are expected to be in the range of 90 minutes; and if you have experienced personnel, onsite surgery, and if you have an established plan to transfer the patient for PCI. Also, PCI has shown to provide greater benefit for patients at higher risk, for example, patients in cardiogenic shock or with heart failure. Fibrinolysis within the 2-3 hour time frame period is a good option when PCI is expected to be delayed in an institution with PCI or in a community hospital setting when long transfer times would delay mechanical perfusion. Pre-hospital fibrinolysis is being explored and beginning to some benefit. The use of facilitated PCI has conflicting data about its use. Well gentlemen, thank you very much, this was an excellent discussion.

SIDNEY SMITH, MD: It’s a pleasure.

DEEPAK L. BHATT, MD: Yes. Thank you very much, Dolph.

DOLPH HUTTER, MD: And thank you for joining us. I’m Dolph Hutter.

Related References/Reading:

1.       Antman EM, Anbe DT, Armstrong PW, et al. ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction; A report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2004 Aug 4;44(3):E1-E211.

2.       Keeley EC, Boura JA, Grines CL. Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials. Lancet. 2003 Jan 4;361(9351):13-20.

3.       Hochman JS, Sleeper LA, Webb JG, et al. Early revascularization in acute myocardial infarction complicated by cardiogenic shock. SHOCK Investigators. Should We Emergently Revascularize Occluded Coronaries for Cardiogenic Shock. N Engl J Med. 1999 Aug 26;341(9):625-34.