Reviewing IABP Use After Recent Clinical Trials
Dr. Patel, along with Drs. Divaka Perera, Matthew Lumley, and Nico Pijls, recently wrote an
editorial in Circulation: Cardiovascular Interventions1 that discussed the impact of clinical trials IABP-SHOCK II, BCIS-1, and CRISP-AMI on intra-aortic balloon pump use in the cath lab.
Dr. Patel, why write this editorial looking at IABP use and current clinical trial data?
We do a lot of things for patients that we take care of in the cath lab, everything from diagnostic studies to coronary intervention with stents, to use of new technologies. Recently, we have begun to utilize several types of devices to help patients get through the procedure. One of the most common in cath labs around the country is intra-aortic balloon counterpulsation or intra-aortic balloon pumps (IABPs). IABPs are a common device that many of us have ‘grown up’ learning to use as we became interventional cardiologists. Many cath labs and intensive care units use the device to support patients. Interestingly, over the past five years, there has been a significant increase in the amount of clinical trial data. The co-authors on the editorial, along with myself, participated in some of these trials. We felt that as these randomized trials come out, as with any clinical trial, that the data provide some answers, but also lead to some questions. We wrote the editorial with the hope of starting to put things in context, with regards at least to counterpulsation. Another one of our goals was just to show the breadth of randomized trials with intra-aortic counterpulsation. As a device, it’s of course something we use frequently, but if you look across different indications, there are several different types of studies done in different eras that may provide us with information. We wanted to utilize the opportunity to put all of that in context.
In the editorial, you called the IABP an “old friend.”
We ask, “is it time to abandon ship or is there hope yet for our old friend?” As interventional cardiologists, we take care of patients along the spectrum of coronary artery disease. Having a device that can be put in quickly, with low complication rates, and that can support the patient acutely through hemodynamic instability, was certainly a significant leap forward. Early on, there may not have been as many trials, although I would say probably more than in other devices. But as they say, when you believe in something, you don’t always do a randomized trial. We don’t have a randomized trial of parachutes, but we all use parachutes when needed and we believe that they help us. When patients get sick, we don’t always have randomized trials on support devices, but we use them, because patients get sick and we feel that they help. In many ways, that’s what counterpulsation was in the first decade or two of its utilization. Dr. Ohman, one of our co-authors on some of the trials, Dr. Stone, and others did study counterpulsation in a rigorous fashion. Certainly, balloon pumps were shown in percutaneous coronary intervention (PCI) settings to have some possible benefit, both clinically and for secondary measures such as re-occlusion and closing of the infarct-related artery. So certainly there was existing data, but as we have improved procedural outcomes, the question has been asked, do we need to rely on the IABP as much? This question brings us into the new era of trials. I would also say that the standard we are applying now for a device is significantly higher. In the CRISP-AMI clinical trial, we looked at infarct size reduction in acute myocardial infarction (MI) patients. We also looked at clinical events. The SHOCK II trial looked at hard clinical events, with all-cause mortality as the primary endpoint. While both infarct size reduction and clinical events are important, I am unaware of many cardiovascular technologies that have reduced mortality. These are sick patients. We do want to help them and reduce their mortality. However, it should be understood that’s a pretty high bar.
What is the patient population under consideration for IABP use?
There are three big groups where I think about the balloon pump as an adjunct to angioplasty: high-risk patients, patients in acute MI without cardiogenic shock, and patients with an acute MI complicated by shock. Randomized trials have looked at these groups. One of the co-authors on the editorial, Divaka Perera, led the BCIS-1 study. BCIS-1 is an intriguing study showing us that acutely, early on, counterpulsation had fairly similar rates of events, hard clinical endpoints of death, MI, etc., but as we followed those patients long-term, out to 51 months, patients who got a counterpulsation device seemed to do better. It’s not fully understood why, but we think that if you get through the acute risk and are able to do more revascularization, those patients may, in fact, benefit. BCIS-1 of course has to be replicated, but the trial is an early, encouraging sign that there are patients at risk where the device supports some clinical events. So that’s one question: In high-risk patients, does the balloon pump add benefit? And certainly there are other devices coming down the pike. In acute MI patients without shock, we know from the initial studies by Dr. Ohman, Dr. Stone, and others, that when patients were urgently coming to the lab and were potentially at risk because of heart failure or they had a high-risk lesion, counterpulsation did, in fact, prevent re-occlusion of the infarct-related artery and might have had a trend towards helping with clinical events. This was in the era before we had some of the new anticoagulants and all of the door-to-balloon time measures. The CRISP-AMI trial was aimed at seeing if there was an infarct size reduction with IABP use. In that trial, we showed that the infarct size in large anterior MIs was similar in both arms and was not reduced by routine IABP use. In all of these trials, it should be kept in mind that many of the patients that became quite sick crossed over to getting a counterpulsation device. Everyone who works in a cath lab knows that if a patient gets really sick, if you have to put a balloon pump in, you can do it fairly quickly, and sometimes it helps stabilize the patient. These studies tell us that, in general, routinely using the balloon pump was probably not indicated, but it’s an old friend that we have handy in our toolbox if patients gets acutely worse. The final set of patients, the population in which operators probably utilize a counterpulsation device the most, are patients with cardiogenic shock. These patients are in hemodynamic compromise. You are trying to open the artery and put in the counterpulsation device either before or after the revascularization event to support it. Most of the time, it is before. The SHOCK II trial randomized patients to receive the counterpulsation device or not, and tried to get people to the cath lab quickly and open up the artery. The first caveat I have is that when patients are in shock, I tend to put the counterpulsation device in first, to support the myocardium and help with revascularization, even though I know it takes 8-10 minutes more. This time frame comes as a result of the CRISP-AMI trial, where patients were randomized to getting an IABP or not, and we showed it only took 8-10 minutes more to put in the counterpulsation device. It did not significantly increase the infarct size or delay door-to-balloon reperfusion time. So putting the IABP in earlier may be of benefit. In SHOCK II, the counterpulsation device was routinely put in, but unfortunately, not always before the revascularization. Those patients had a high mortality event rate, somewhere around 40%. The rate was similar in both arms, but of course, as always, there was some crossover for the very sick. The second caveat of SHOCK II is that it is out to 30 days, with recent data showing similar events out to one year. Even the original SHOCK trial supporting revascularization only showed a difference after six months and so we await the long-term findings of the SHOCK II trial, as with BCIS-1. If this device is put in routinely in shock patients, is there a separation of the curves long-term? I’m not sure there will be, but it is still important to know that this was a device that was safely put in and it did meet the mortality reduction standard.
Can you talk about some of the caveats we should keep in mind as we look at the SHOCK II trial?
First, I want to congratulate the investigators who did the trial. I think just the fact that they were able to randomized 600 shock patients so quickly is an impressive feat, and these investigators are committed to a question that is an important question. The mortality rate that the SHOCK II investigators were looking for was based around 50%, but there was a 40% mortality rate, leading to less power than they anticipated. Of course, there were some crossover patients going over to the other arm, also reducing opportunity to show a difference. Nevertheless, the mortality rates were fairly similar. It may be that the reduced power and lower mortality rate occurred because we have gotten better and better at taking care of these patients. When SHOCK II gets out to six months, it may give us another opportunity to see an effect size and tell us how powered the trial was to see a difference. If you are taking care of patients with shock, even if you opened the artery as fast as possible, if a counterpulsation device wasn’t used, you are faced with a decision at the end of the procedure. Do you send the patient to the intensive care unit and hope with 3 days of inotropic support, intubation, and careful CCU monitoring, the patient will have the same outcome as those who routinely got a counterpulsation device? This is the question SHOCK II hoped to answer. In our clinical practice, if our patient is in extremis, we know they do at least as well with counterpulsation. We sometimes put it in to see if there are ways we can come off: inotropes, maybe help the heart heal faster, and get into a better state. It’s not clearly shown to be a mortality reduction, but certainly an IABP may help you with management of the patient.
Can you share more about crossover in clinical trials?
These are issues that we face in all these types of trials, because they are large, simple trials regarding how we manage patients. An operator may be faced with the same question I just described. Perhaps their patient was randomized to no counterpulsation device, but there is something about this patient, who is getting sicker, that the interventionalist sees. At that point, they may cross the patient over and still put in the counterpulsation device, or moreover, at least in SHOCK II, they might have used other types of left ventricular assist devices that aren’t fully delineated. The team may have used other types of support that may keep the patient alive out to 30 days, and again, skew our ability to understand which strategy is the best. Now, the true trialist would say it is intention to treat, so you go down the arm of not using counterpulsation, and if the patient gets sick enough, you use it. I think that’s probably fair; the only problem I have is that we want to, if possible, identify what the interventionalists were seeing or what they were thinking when they crossed over that patient, so we can have the same clinical care pattern in identifying the particular features of those patients. This is something we are looking at in the CRISP trial and I assume in future SHOCK II analyses, more information will emerge regarding those patients that crossed over.
Where are we in terms of creating a risk stratification system?
We have to continue to work on trying to help clinicians with this. I think the take-home message is as follows: first, we seem to get a sense across the board, at least for acute MI patients, that routine insertion of the counterpulsation device doesn’t seem to have a clinical benefit at this point. For patients with an acute MI that is an anterior MI or they are also in cardiogenic shock, it is not clear that a balloon pump should be placed in all patients. Yet there do seem to be patients in this category that deteriorate and, in the clinical trials, get a counterpulsation device. We would love to be able to identify those earlier via a risk stratification system. In our database, it looks like those patients that are slightly older, maybe female, maybe having their blood pressure drop a little faster in the middle of a case, you are not getting good flow — these are patients where the counterpulsation device seems to be used in the trials and these factors may be triggers for interventionalists to use counterpulsation devices to support patients. For high-risk PCI, it is really unknown. BCIS-1 showed that utilization of a counterpulsation device supported patients long-term. Trial investigators used the Jeopardy score to look at the amount of myocardium at risk and coronary lesions. In the end, what interventionalists tend to ask is, what’s the ventricular function and how much of the myocardium is at risk with the intervention? Then, based on that, they make a decision whether they need any support versus no support. If they need support, then a decision has to be made about the available devices. In this space, I would say counterpulsation certainly has been shown, with BCIS-I and other studies, to have potential benefit.
There is also a low risk of vascular complications and bleeding with the use of an IABP.
CRISP-AMI, BCIS-1, and IABP-SHOCK II all demonstrate that the counterpulsation device is a mature technology. It can now be placed through a 7.5 French sheath, and the rate of vascular complications, bleeding, and significant embolic events is pretty low. It seems to be similar between the randomized arms, meaning that we can put the device in safely. Clearly we need more trial data on evaluating counterpulsation versus some of the percutaneous ventricular assist devices to answer questions such as: Which device should we use? How long does it take to put the device in? How safely can we put it in? What’s the efficacy? Trials to answer these questions in acute MI patients are needed and certainly, they are needed in shock patients. In elective PCI, of course, there has been some data, and those data, depending on how people look at them, show small, if any, differences. It will be something we will be focusing on, based on how safely and quickly you can put in the device, and which strategy is most cost effective down the road for us when we take care of our PCI patients.
Disclosure: Dr. Patel reports research grants from AstraZeneca, Johnson and Johnson, Maquet, Medtronic, the NHLBI, and AHRQ.
Dr. Manesh R. Patel can be contacted at manesh.patel@duke.edu.
Reference
- Perera D, Lumley M, Pijls N, Patel MR. Intra-aortic balloon pump trials: questions, answers, and unresolved issues. Circ Cardiovasc Interv. 2013 Jun 1;6(3):317-21. doi: 10.1161/CIRCINTERVENTIONS.113.000336.
