STEMI Patients With Persistent Ischemia After PCI: A Potential Target for IABP?

PARIS, France—When used at the right time and in the right patients, intra-aortic balloon pumps (IABPs) might improve outcomes following STEMI, 6-month results from the SEMPER-FI pilot study suggest.

The single-center but prospective and randomized study of 100 patients enrolled only those with large acute STEMI who continued to have persistent ischemia after primary PCI, Lokien van Nunen, MD, PhD (Catharina Hospital, Eindhoven, the Netherlands), told attendees during a hotline session last week at EuroPCR. “The intra-aortic balloon pump is the most widely used mechanical circulatory support device due to its ease of use, fast manner of insertion, and low complication rate,” he said.

The strategy tested here, he explained to TCTMD, is based on the “idea of decreasing infarct size by making the heart work less hard and improving coronary blood supply and oxygen supply.”

Eight years ago, CRISP-AMI dashed hopes for IABP therapy when it failed to show a reduction in infarct size or improvement in clinical outcomes when deployed prior to primary PCI in high-risk STEMI patients without cardiogenic shock. Subsequently, though, a substudy from that trial hinted that better patient selection could translate into lower mortality with IABP use.

The SEMPER-FI researchers aimed to explore that possibility further. They determined that a trial would need 400 patients to be adequately powered for the primary composite endpoint of mortality, necessity of mechanical circulatory support, or hospital readmission for congestive heart failure at 6 months. “But due to the reason that all the large randomized IABP trials in the recent past have shown negative results, we decided to start with a pilot study with 100 patients to test our hypothesis and methodology,” van Nunen said in his presentation.

While the EuroPCR report is “encouraging, in that this might be an opportunity to use [IABP] therapy for a complicated group of patients—patients who have failed standard of care, which is to open the artery as fast as possible—I don’t think the evidence by any stretch at this point is supportive of doing it routinely in our patients,” Manesh Patel, MD (Duke University Medical Center, Durham, NC), lead investigator of the CRISP-AMI trial, commented to TCTMD.

Instead, it emphasizes “the importance of trying to study this indication,” he said, adding, “I would hope that we could get the entire randomized study done and then evaluate it, because I think that’s where the real value will be.”

Primary Endpoint Trends in the Right Direction

All of the 100 patients presented with large acute STEMI (summed ST-deviation ≥ 15 mm) and had persistent ischemia after primary PCI (ST-segment resolution < 50%); none were in cardiogenic shock requiring immediate hemodynamic support. After PCI, they were randomized 1:1 to IABP or no IABP for 12 to 24 hours. Mean duration of IABP use was 15 hours.

By 6-month follow-up, one patient in the IABP group had experienced a primary endpoint event, specifically death, compared with four patients in the control group (2% vs 8%; P = 0.16), two of whom died. For mortality alone, the P-value was 0.56. Infarct size did not differ between the two groups.

Acknowledging to TCTMD that SEMPER-FI, while a good start, is too small to provide a definitive answer, van Nunen said: “At least in this trial we have a clear sign that there is a benefit of IABP therapy in patients presenting with large acute myocardial infarction, especially [when] complicated by persistent ischemia after primary PCI.

“At this point in the clinical scenario you have reached epicardial reperfusion, so the epicardial blood flow is good, but there is still ischemia at the microvascular level,” van Nunen continued. “And at that time, coronary autoregulation is completely shut off, making coronary blood flow directly dependent on perfusion pressure. Augmentation of that perfusion pressure by IABP can lead to better oxygen supply and thereby limitation of infarction size. At least, that’s the theory.” Preclinical studies, nonprespecified substudies, and now this pilot study all point in the same direction, he added.

Not Yet Proven

“For some time,” Patel said, “people have considered intra-aortic counterpulsation as a possible therapy for failed or nonoptimal reperfusion, or rescue reperfusion—patients who’ve had an artery opened in the setting of acute MI and yet afterwards have no reflow or slow flow [or] microvascular obstruction. Sometimes people refer to it as ischemia reperfusion injury, [where] the artery’s open but there’s such a thrombotic burden that it goes down and causes infarction in the microvasculature of the muscle.”

But “importantly,” he added, “this is something many therapies have tried to improve on. Aside from opening the artery as fast as possible, to date nothing has gotten yet fully to market for ischemia reperfusion injury by itself as a [therapeutic target].”

Patel pointed out that in CRISP-AMI, patients were randomized and the IABPs inserted prior to PCI. There, he said, the idea was to “prevent some of those patients from having as big an infarct by unloading the ventricle and/or having them deteriorate. Clinically, there was potentially a signal, but infarct size, the primary endpoint, wasn’t different.”

Along with van Nunen, Nico Pijls, MD, PhD (Catharina Hospital), and others, Patel co-wrote a 2016 review in the American Journal of Cardiology that outlined what might be needed for IABP therapy to work effectively, given that trials have looked at heterogeneous populations. “The idea is that the physiologic principle of increasing diastolic augmentation makes sense, but of course a lot of things make sense that we have to then test and prove,” he said.

To TCTMD, van Nunen said there are few risks to the IABP approach tested in SEMPER-FI. There was slightly more bleeding, especially when IABPs were used in patients taking glycoprotein IIb/IIIa inhibitors, but none of those bleeding events resulted in death. “We saw very few complications but we have to be careful [in making assumptions], because we are a dedicated center and our interventional cardiologists do these procedures quite a lot and implant a lot of IABPs, so they are quite skilled at it,” he cautioned.

Sunil Rao, MD (Duke University Medical Center), who commented on the study for TCTMD, also had some words of caution. Given how hard it is to conduct a trial in the STEMI setting, “the researchers deserve a lot of credit for trying to at least answer this question,” he noted. “Having said that, I really don’t know what to take away from this.”

That’s because the results come from an underpowered analysis, Rao explained. The reporting of “early looks” at data is “becoming more and more common at interventional conferences,” he said, adding, “It misinforms the clinical community, or has the potential to,” if people give too much weight to trends based on a small number of events.