Use of Impella increased survival in DanGer Shock

The DanGer Shock trial compared survival using left ventricular (LV) mechanical circulatory support with the Impella CP microaxial flow pump in patients with ST-elevation acute myocardial infarction (STEMI) complicated by cardiogenic shock (AMICS) to conventional guideline-driven treatment. This was the first adequately powered randomized trial to address whether mechanical circulatory LV support with Impella CP can improve survival in AMICS. 

The trial's findings revealed a significant improvement in 180-day mortality rates among patients who received the Impella CP device compared to those receiving conventional guideline-driven treatment. 

"In this trial, 180-day mortality was statistically, significantly lower with the use of Impella CP compared with the usual care. The flip side was that the complication rates were higher with the Impella device. So things like limb ischemia, vascular complications, bleeding and the use of renal replacement therapy. But overall, this is the first strategy that we have seen since 1999 that reduces mortality in acute cardiogenic shock. So I really think this is a very, very important study," Rao explained.

He explained that the 1999 Shock Trial showed the only strategy that really works to reduce mortality in cardiogenic shock is the prompt revascularization of the infarct artery. 

"Since that time, we've tried all kinds of things to reduce mortality, and we really haven't. There's a really attractive hypothesis that LV unloading or support of the LV in that particular situation may in fact improve survival, because it may not be sufficient to simply reestablish flow to the infarcted myocardium when a patient is already in extreme distress. And that's really what this trial was designed to test," Rao said. 

This was echoed by the trial's lead author in a statement on the trial during ACC.

“This is the first time in a very long time that we have a positive study for managing cardiogenic shock,” said Jacob E. Møller, MD, professor in the Department of Cardiology at the Odense University Hospital, Denmark, and a consultant at the cardiac intensive care unit of Copenhagen University Hospital Rigshospitalet. “I think this will be a routine device that will be used in these desperately ill patients.”

The trial enrolled 360 patients at 14 centers in Denmark, Germany and the United Kingdom. Patients who suffered out-of-hospital cardiac arrest with coma and increased risk of brain damage were excluded from the trial. Researchers randomly assigned patients to receive standard care or standard care plus treatment with an Impella CP pump. Participants were randomized before, during or up to 12 hours after receiving treatment in the cath lab.

What other shock trials say about the best treatment strategy

Rao touched on numerous other trials that have looked at cardiogenic shock, including previous European trials involving devices like ECMO (extracorporeal membrane oxygenation) and intra-aortic balloon pumps (IABP). He highlighted the methodological differences and selection criteria that distinguish the DanGer Shock trial, suggesting a more refined approach to patient selection and endpoint assessment. The biggest difference in those trials compared to DanGer Shock was the use of a 30-day assessment rather than the 180 days in the latest trial. 

"That's important because even in the Shock Trial that has established a standard of care using primary PCI, that benefit didn't really emerge until 180 days. So that 30-day endpoint may in fact just be too early to show a benefit in any kind of strategy. So while it's tempting to say that IABP doesn't work, ECMO doesn't work, but Impella works as a mechanical support device in shock, we have to be a little bit careful because I think the DanGer Shock trial is a little bit more of a contemporary design based on what we know from those other trials," Rao explained.

The optimal timing of interventions and when to use mechanical support is another area of debate in shock patients, Rao said. The ongoing STEMI-DTU trial is looking at implementing Impella CP and then waiting 30 minutes prior to PCI to increase myocardial salvage and to help reduce the infarct size. That trial is based on animal models, where the wait reduced damage to the heart. 

The National Cardiogenic Shock Initiative, which includes 80 hospitals in 29 states, developed a protocol for quick placement of the Impella heart pump, PCI, and right heart monitoring to rapidly reduce the use of inotropes. The initial pilot study shown improvement in survival rates from 50% to 72%. That protocol is now being tested in the ongoing RECOVER IV Trial.