DanGer Shock Randomized Control Trial FAQs

What is the significance of the DanGer Shock trial?

• The significance of the DanGer Shock trial lies in its milestone findings for cardiology, potentially reshaping patient care by establishing routine Impella use as a life-saving intervention for STEMI patients with shock. These findings could inform future guidelines, influencing the management of AMICS and potentially reducing mortality rates in this patient population.
• The NEJM editorial by Sunil V. Rao, MD accompanying the paper in which the DanGer Shock results were published states that the findings represent a milestone for the field: “These striking results mark the first treatment strategy to show a benefit in patients with AMICS since the SHOCK trial, published in 1999, established percutaneous coronary intervention as the cornerstone of treatment.”

What aspects of the DanGer Shock RCT helped differentiate it as the only MCS device trial to demonstrate improved survival in AMICS?

• DanGer Shock focused solely on STEMI-related shock, excluding other causes of shock.
• The Impella device used in the treatment arm provided circulatory support, ventricular unloading, and coronary perfusion.
• The extended 180-day follow-up period revealed an incremental survival benefit in Impella-treated patients.
• The study considered device implantation timing.

What mortality results have been seen in previous shock trials?

• The results of the IABP-Shock II trial showed no difference in mortality in STEMI and NSTEMI-related shock. Furthermore, the trial excluded comatose patients with fixed dilated pupils not induced by drugs.
• In the ECLS-Shock trial, the absence of a mortality benefit in STEMI and NSTEMI-related shock appeared to be consistent across multiple subgroup analyses, including STEMI or NSTEMI, lactate >6 mmol/L, or receipt of CPR. Patients who had not undergone resuscitation exhibited a similar mortality rate to those who had undergone resuscitation.

How will the results of the DanGer Shock trial impact patient care today?

• DanGer Shock results highlight the first treatment strategy to show benefit in patients with AMICS since the SHOCK trial published in 1999, which established percutaneous coronary intervention as the cornerstone of treatment.
• Adoption of the DanGer Shock trial results in the STEMI care network will have a significant survival impact for the large patient population with STEMI complicated by shock. In the United States, 750,000 patients experience a STEMI heart attack each year¹ and up to 10.1% of STEMI patients develop cardiogenic shock.² This translates to approximately 75,000 cases of STEMI complicated by shock. 
• The DanGer Shock study established that routine use of Impella will save one life for every eight treated patients which translates to approximately 9,000 potential lives saved in US alone. Cardiology societies, health care systems, STEMI care pathways and cath lab leadership teams should act promptly to ensure patients with STEMI complicated by shock have timely access to Impella support, thereby reducing mortality.
  • 12.7 absolute reduction in mortality, NNT=8, hazard ratio, 0.74; 95% CI, 0.55 to 0.99; p=0.04

How will the results of the DanGer Shock trial impact guideline recommendations?

• The guideline committee will be responsible for deciding on the guideline recommendation based on these results. 
• The DanGer Shock study met its primary endpoint of improved survival at 180 days vs. standard of care. Similar groundbreaking RCTs, including Hochman et al., missed their primary endpoint, yet have led to Class I guideline recommendations.
• In DanGer Shock, death from any cause at 180 days (primary end point) occurred in 82 of 179 patients (45.8%) in the microaxial-flow-pump group and in 103 of 176 patients (58.5%) in the standard-care group (hazard ratio, 0.74; 95% CI, 0.55 to 0.99; P-0.04)  
• In DanGer Shock, the number needed to treat (NNT)  of 8 is similar in magnitude to other landmark trials (such as the original SHOCK trial and the Culprit Shock trial) that provided the Level of Evidence B needed (single RCT) to inform guideline recommendations.
  • 12.7 absolute reduction in mortality, NNT=8, hazard ratio, 0.74; 95% CI, 0.55 to 0.99; p=0.04
• Other large clinical studies also found that Impella improves survival in AMICS. Inova (2019), the National Cardiogenic Shock Initiative study (2021) and the Japanese registry for percutaneous ventricular assist device (J-PVAD) study (2022) demonstrated 82%, 71% and 81% survival with Impella, respectively.

What insights can we learn from DanGer Shock regarding best practices in AMI cardiogenic shock?

• Fundamentally, DanGer Shock confirms that routine use of Impella improves outcomes in AMI cardiogenic shock due to STEMI. 
• Designed 10-years ago, DanGer was not designed to evaluate best practices that have developed in the last decade, such as pre-PCI unloading (84 of 179 patients were randomized before PCI with Impella placed pre-PCI), the use of invasive hemodynamics through right heart catheterization, aggressive weaning of inotropic drugs, escalation to Impella 5.5/RP/ECpella when indicated, as well as the latest vascular access and anticoagulant management techniques. These advances in treatment strategies have been associated with further improvement in survival in multiple contemporary registries and are the subject of the RECOVER IV RCT, a treatment strategy trial building on both DanGer Shock and the above-mentioned progress in therapeutic management.

Back to top.

What patient selection criteria set the DanGer Shock RCT apart from other MCS device trials?

• The DanGer Shock trial focused specifically on STEMI-related shock and excluded other causes of shock, such as comatose out-of-hospital cardiac arrest (OHCA) with persistent Glasgow Coma Scale (GCS) <8. These criteria allowed the study to focus on patients who would likely benefit from hemodynamic support. Include link to inclusion/exclusion  

What are the unique characteristics of the device used in DanGer Shock?

• Impella CP® was the microaxial flow pump used in the treatment group. Impella CP has a unique mechanism of action and provides circulatory support, ventricular unloading, and coronary perfusion. Impella CP provides blood to the end-organs and to the heart itself, while simultaneously allowing the heart to rest.

What is the impact of the timing of device implantation?

• In the Impella arm of the DanGer Shock trial, Impella was placed at the time of shock diagnosis, which may have been before or after PCI. Consequently, 84 of the 179 patients in the Impella arm had Impella placed pre-PCI. 
• In the IABP-Shock II study, the subgroup analysis evaluating IABP pre-PCI vs post-PCI showed no difference in 30-day mortality or 6-year mortality at long-term follow-up, and no difference in 48-hours lactate clearance. 
• ECLS-Shock recommended ECMO placement pre-PCI as the preferred study protocol; however, due to various challenges, only 21.9% had ECMO placed pre-PCI. In addition, there was no-difference in 48-hour lactate clearance vs control.

Were out-of-hospital cardiac arrest (OHCA) patients excluded from the DanGer Shock study?

• Not all OHCA patients were excluded. Only OHCA patients who remained comatose upon arrival to the cath lab, with a persistent Glasgow Coma Scale <8 were excluded. Additionally, cardiac arrest occurring in the ambulance or after arrival to the hospital was not an exclusion criterion. In the Impella arm, 21.8% patients, and in the control arm 18.8%, were resuscitated before randomization.

Back to top.

In the DanGer Shock trial, what is the significance of the longer 180-day follow up endpoint?

• A divergence of survival curves was seen in DanGer Shock. The widening of survival curves seen in the DanGer Shock trial was also seen in the SHOCK trial and is accretive to the positive effect of immediate PCI, but was not seen in ECLS-Shock³ or in IABP-Shock II⁴ MCS trials.     

Does the adverse event rate overshadow the significant survival benefit in the DanGer  Shock trial? 

• Adverse events in DanGer Shock do not overshadow the significant survival benefit demonstrated with routine Impella use in STEMI-related cardiogenic shock.

How do the adverse events in the DanGer Shock trial align with other trials?  

• The increased risk of adverse events observed in the DanGer Shock trial⁵ is consistent with findings from other studies such as IABP-Shock II⁶ and ECLS-Shock.⁷ 
• Preventing complications through implementation of best practices remains a top priority. 
  While the current literature demonstrates the impact of adverse events, such as bleeding, on mortality, it is expected that advancements in technology, employing best practices, and training efforts aimed at reducing adverse event rates will lead to greater mortality benefits for patients.

What is the impact of survival bias in the DanGer Shock trial?

• The increased risks of adverse events in the Impella group could, in part, be attributed to a survival bias, as more patients died early in the standard-care group, and thus they did not experience adverse events.  
• Surviving patients may face heightened risks of adverse events, such as greater use of temporary renal replacement therapy, and hemolysis due to prolonged use of support and acute kidney failure, which may be aggravated further by bleeding and sepsis. 
• Of the 75 patients receiving the microaxial flow pump who required temporary renal support, all but three recovered renal function.

By Day 30:

• 18 more patients died in the standard care group from cardiac failure, with the majority dying on day one, resulting in shorter ICU stay in the standard care group.  

By Day 90: 

• Only 3 (1.7%) patients remained on dialysis in the Impella group and 1 (0.6%) in the control) 
• By the end of trial follow-up (180 days) no patients in the Impella arm remained on dialysis

Was mortality in the control arm of DanGer Shock especially high?

• Excess mortality after day 30 has also recently been shown for NCSI by Babar Basir et al. (JAHA 2023). 
• Mortality in patients eligible for DanGer Shock was estimated to be 63.5% at 30 days based on German registry data (Schrage and Thiele, Eur Heart J, 2021).
• Looking at patients excluded from DanGer Shock, those with OHCA had 30-day mortality of 48.8% and those without OHCA had 30-day mortality of 64.4%; therefore, 46.5% mortality at 30 days in the control group seems appropriate given phenotype and hemodynamic compromise.

Why was the median ICU length of stay in the standard care group only 3 days ?

• Davodian et al., in AJC 2021, showed that median time to death from first contact with EMS is 13 hours for those dying of refractory cardiac failure, as opposed to 140 hours for neurological death and 137 hours for multiorgan failure among 1716 AMICS patients.
• By excluding the majority of OHCA patients, patients selected for DanGer Shock were at risk of dying early. This helps to explain the ICU length of stay in DanGer Shock being shorter than in previous studies with high prevalence of OHCA patients, who due to TTM and neurological prognostication, remain in the ICU longer.

Back to top.