Routine use of Impella CP for STEMI-related cardiogenic shock confers survival benefit
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Key takeaways:
- Risk for death was lower with the pump vs. standard care only, but incidence of adverse events was elevated.
- The trial provides new insights on mortality in patients with STEMI and cardiogenic shock.
ATLANTA — In the DanGer-Shock trial, routine use of a microaxial flow pump, on top of standard care, led to a lower risk for death compared with standard care only for treatment of patients with STEMI and cardiogenic shock.
At 180 days, death from any cause occurred in 45.8% of patients assigned to treatment with a microaxial flow pump (Impella CP, Abiomed) plus standard care as soon as STEMI-related cardiogenic shock was diagnosed compared with 58.5% of those assigned standard care only (HR = 0.74; 95% CI, 0.55-0.99; P = .04). Mean number of days alive out of hospital was 82 in the pump group and 73 in the standard care group, Jacob Eifer Møller, MD, PhD, DMSc, reported at the American College of Cardiology Scientific Session.
DanGer-Shock is the first mechanical circulatory support device randomized controlled trial to demonstrate a survival benefit in patients with acute MI and cardiogenic shock, according to a press release from Abiomed.
However, researchers reported a higher incidence of adverse events including severe bleeding, limb ischemia, hemolysis, device failure or worsening aortic regurgitation in the pump group (24% vs. 6.2%; relative risk = 4.74; 95% CI, 2.36-9.55). A surprise finding, Møller said, was more patients in the pump group requiring renal replacement therapy: 41.9% vs. 26.7% (RR = 1.98; 95% CI, 1.27-3.09).
Prior to DanGer-Shock, the effects of temporary mechanical circulatory support with Impella CP in patients with STEMI complicated by cardiogenic shock was unclear, according to the researchers.
DanGer-Shock included 360 participants at 14 sites in Denmark, Germany and the United Kingdom from 2013 to 2023; the trial began in Denmark only but was expanded to Germany and the U.K. because of slow enrollment, Møller said. Patients were randomly assigned to Impella CP plus standard care or standard care only. The median age was 67 years and 79% were men.
“We targeted the very sickest population with STEMI and shock,” Møller said. The researchers excluded patients who were resuscitated after out-of-hospital cardiac arrest and remained comatose on arrival as well as those with overt right ventricular failure.
All patients were in SCAI-CSWG stage C, D or E shock at the time of admission. Cardiogenic shock was defined as hypotension, end-organ hypoperfusion with an arterial lactate level of 2.5 mmol/L or higher and left ventricular ejection fraction of less than 45%.
Median time from onset of STEMI symptoms to randomization was 4 hours. Median LVEF was 25%. Median systolic BP was 82 mm Hg.
Culprit-vessel PCI was performed in 96% of patients and emergency CABG in 1.4%.
Device placement was successful in 95% of patients assigned to the pump group; 1.7% of patients assigned to the pump group crossed over to standard care and 3.3% had unsuccessful pump placement.
“The study is not testing medical therapy vs. a pump; it’s testing a very aggressive strategy of opening the vessel, giving drugs and, if needed, a machine vs. putting the machine in up front,” Moller said during the press conference.
The results cannot be extrapolated to other causes of cardiogenic shock, including out-of-hospital cardiac arrest, non-STEMI and nonischemic cardiogenic shock, Moller said.
Discussing the findings during a press conference, Robert Roswell, MD, FACC, FACP, associate dean for diversity, equity and inclusion and professor of cardiology and science education at the Donald and Barbara Zucker School of Medicine at Hofstra/Northwell, co-director of the Cardiac Intensive Care Unit and associate director of the cardiology fellowship at Northwell Lenox Hill Hospital, and chair of the ACC Critical Care Cardiology Council, said this is “a groundbreaking trial.”
“The last trial that showed a positive effect in cardiogenic shock was in 1999. So this is 25 years later that we actually have a new trial that shows an intervention that can actually reduce mortality in patients who have STEMI and cardiogenic shock,” Roswell said.
“This is an outstanding trial and it definitely will change practice.”
During the press conference, Møller and Roswell said news of the FDA having concerns about the safety of the Impella pumps does not detract from the DanGer-Shock findings.
“There has been a lot of discussion recently about perforation of the heart, but we didn’t see that in our trial,” Møller said. “But the number in our trial was 360 and the perforations are a small number out of hundreds of thousands of devices. I’m sure it can happen, and I think the key here is that if you use this device, you have to be sure that the pathophysiology is there and that the patient is sick enough to take the risk. We have a huge burden to go out now and do better with these complications. We cannot extrapolate [these results] to a lot of other cases. We have to be very straight and say, this was the sickest of the sickest.”
“What we see in the trial is the implementation of the device,” Roswell said. “But a lot of the management of the device happens in an ICU setting. It’s important that you have physicians and teams who are very familiar with these devices to understand the hemolysis, the ischemia, the other potential complications like perforations. The team involved is very important. The care on the back end is also impacting the reduced mortality.”
References:
- Moller JE, et al. N Engl J Med. 2024;doi:10.1056/NEJMoa2312572.
- Randomized controlled trial confirms Impella CP improves survival in heart attack with cardiogenic shock. https://www.abiomed.com/about-us/news-and-media/press-releases/rct-confirms-impella-cp-improves-survival-in-heart-attack-with-cs. Published April 7, 2024. Accessed April 8, 2024.
Perspective
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It used to be that cardiogenic shock is where clinical trials went to rest in peace. There has been nothing positive in this space since the 1990s. So, this trial is huge for several reasons. No. 1, if it was a negative trial, it would have set us back tremendously. When we are doing these high-risk cases, the interventional cardiologist can immediately see the hemodynamic effects of implanting these devices. It is very compelling. When you see all this negative press about Impella, you wonder, why are people still using it? But as an interventional cardiologist, when you are just trying to keep that patient alive through the procedure and the pressure drops to practically zero, you put a device in and you have flow and cardiac output, and you can seemingly salvage some of those patients. A lot of us felt that in the heat of that moment, we were doing something beneficial to the patients. The problem is, without a clinical trial, we have no way of knowing that. All you see in clinical practice is the complications. DanGer-Shock showed us the balance between efficacy and the complications. We knew complications were going to be higher with these devices. But what we didn’t understand was how much benefit there would be on the mortality side.
This shows a very nice signal. We will have to look at the follow-up, and we will have to look to the ongoing RECOVER-4 trial for corroboration. This saved microaxial left ventricular support devices, at least for now. It allows us to at least feel what we have clinically felt compelled to do to save a life seems to be supported by at least one trial.
This was a tough trial to do, and the 10+ years it took to enroll is emblematic of how hard it is to enroll in these trials. However, the incidence of cardiogenic shock is actually going up because of our aging population. And those are the people who have more complications and have higher risk for vascular and bleeding complications. It is also going up in women, who have smaller blood vessels, smaller femoral arteries and higher bleeding risk and CV complication rates. There were very few women involved in this trial, only about one in five. We are going to have to do our due diligence to understand the safety vs. efficacy relationship in women with cardiogenic shock. This is going to boil down to hemodynamic benefit that may end up saving a life vs. the downside of putting this large-bore vessel in a very sick patient.
A lot of us were stunned by the results of that paper. We had been so used to seeing negative trials coming from the cardiogenic shock space. We almost assumed it was going to be a neutral trial.
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Møller JE, et al. Joint American College of Cardiology/New England Journal of Medicine Late-breaking clinical trials III. Presented at: American College of Cardiology Scientific Session; April 6-8, 2024; Atlanta.
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