A Decade of Progress in Cardiogenic Shock Treatment: DanGer Shock RCT, a Milestone in Cardiogenic Shock Trials

• The DanGer Shock Randomized Control Trial (RCT) had a strict criteria of cardiogenic shock (CS): BP < 100 mmHg, median arterial lactate >2.5 mmol/L and LVEF < 45% on echocardiogram.
• The study only included a STEMI population and excluded patients that had an out-of-hospital cardiac arrest.
• The strict inclusion criteria impacted recruitment and study duration.
• The first 100 patients that were included in the study had median lactate levels of 5.5 mmol/L; 94% of them were on vasopressors and inotropes.
• The first 100 patients that were treated in DanGer Shock RCT achieved TIMI 3 flow in < 70% of patients, which is lower than in National Cardiogenic Shock Initiative (NCSI) Study, e.g., TIMI 3 flow of 92% at the end of the procedure, and the German studies (the CULPRIT SHOCK trial) and others have also had higher TIMI 3 flow.

The DanGer Shock RCT was conducted over 10 years, during which specialists had much to learn about the management of acute myocardial infarction (AMI) due to cardiogenic shock (CS). Clinical practice has changed immensely from the start of the NCSI Study eight years ago to nowadays, including best practices such as weaning and escalation protocols and systematic care. While these best practices were not incorporated into the DanGer Shock trial design, they might have influenced the local standard of care at participating sites. This could be a really important aspect of how the trial results are viewed.

The fundamental points to take into consideration when discussing the findings of DanGer Shock trial are: how much ECMO was utilized within the control arm and how much crossover had occurred within the study. 

DanGer Shock RCT Design

The DanGer Shock trial started in Denmark in 2012, and the first patient was enrolled in January 2013. Denmark has a unique system with four large tertiary care centers. The vast majority of AMI patients present to one of those four hospitals. The study investigators recruited patients who had AMI CS and were randomized to either treatment with Impella CP® versus those that were treated with standard of care (SoC).

The SoC was left to the operators’ discretion, but the use of a balloon pump and extracorporeal membrane oxygenation (ECMO) was allowed in the study.

Only 5% of AMI patients suffered CS according to the strict definitions of the trial protocol: BP < 100 mmHg, median arterial lactate >2.5 mmol/L and the patients had to have an echocardiogram that showed an LVEF < 45%. The study only included a STEMI population and did not include NSTEMI; hence, about 100 patients were recruited over five years, and then the trial was expanded to include sites in Germany. 

Contribution of the DanGer Shock RCT vs Earlier CS Studies 

The investigators excluded patients with out-of-hospital cardiac arrest. About 50% of patients who present in CS have concomitant cardiac arrest, but cardiac arrest has a disease process of its own and patients frequently have concomitant neurological injury. Mechanical hemodynamic support with devices such as LVAD or temporary MCS after this neurologic insult occurred cannot chance the outcome of these injuries. 

The investigators were permitted to include patients who had cardiac arrest under professional surveillance, for example, in the ambulance coming into their centers or in-hospital arrests. The first 100 patients included in the study had median lactate levels of 5.5 mmol/L; 94% were on vasopressors and inotropes.

The first 100 patients treated in the DanGer Shock RCT achieved TIMI 3 flow in less than 70% of patients, which is lower than in NCSI. For example, the TIMI 3 flow was 92% at the end of the procedure, and German studies and others also had higher TIMI 3 flow.

The Future

The RECOVER IV RCT uses the best practices learned from NCSI. It is a strategy trial looking at whether mechanical circulatory support (MCS) devices emphasizing left ventricular unloading are more beneficial than our current SoC. There are some fundamental differences in practice patterns and comfort levels with MCS management between the US and Europe.