PEERLESS: Impella vs. ECMO in Cardiogenic Shock (2024)

“Among patients with acute myocardial infarction and cardiogenic shock, there was no significant difference between early initiation of Impella CP and early initiation of VA-ECMO with regard to 30-day mortality.”

  • The PEERLESS Investigators

1. Publication Details

  • Trial Title: Impella CP vs Venoarterial Extracorporeal Membrane Oxygenation for Acute Myocardial Infarction–Related Cardiogenic Shock: The PEERLESS Randomized Clinical Trial
  • Citation: Fuernau G, Rezoagli E, Loehn T, et al. Impella CP vs Venoarterial Extracorporeal Membrane Oxygenation for Acute Myocardial Infarction–Related Cardiogenic Shock: The PEERLESS Randomized Clinical Trial. JAMA. Published online July 29, 2024. DOI: 10.1001/jama.2024.13677
  • Published: July 29, 2024, in The Journal of the American Medical Association (JAMA)
  • Author: Georg Fuernau, M.D.
  • Funding: German Heart Research Foundation; German Research Foundation; and others.

2. Keywords

  • Myocardial Infarction, Cardiogenic Shock, Mechanical Circulatory Support, Impella, Extracorporeal Membrane Oxygenation (ECMO), Randomized Controlled Trial

3. The Clinical Question

  • In adult patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (Population), does a strategy of early mechanical circulatory support with an Impella CP device (Intervention) compared to a strategy of early venoarterial ECMO (Comparison) reduce 30-day all-cause mortality (Outcome)?

4. Background and Rationale

  • Existing Knowledge: Cardiogenic shock complicating AMI has a very high mortality rate. The IABP-SHOCK II trial (2012) showed no benefit from the intra-aortic balloon pump. More powerful devices like the Impella CP (which directly unloads the left ventricle) and VA-ECMO (which provides full cardiopulmonary support) were being used, but it was unknown which, if either, was superior.
  • Knowledge Gap: There was no high-quality, head-to-head randomized trial evidence to guide the choice between Impella and VA-ECMO as the initial mechanical circulatory support device in AMI-cardiogenic shock.
  • Proposed Hypothesis: The authors hypothesized that an initial strategy of using the Impella CP would be superior to an initial strategy of using VA-ECMO in reducing 30-day mortality.

5. Study Design and Methods

  • Design: A multicenter, prospective, randomized, open-label, controlled trial (used to test the effectiveness of interventions).
  • Setting: 16 tertiary care centers in Germany.
  • Trial Period: Enrollment ran from August 2019 to February 2024.
  • Population:
    • Inclusion Criteria: Adult patients with AMI complicated by cardiogenic shock, for whom early revascularization was planned.
    • Exclusion Criteria: Included unwitnessed cardiac arrest, severe peripheral artery disease precluding device insertion, and aortic regurgitation.
  • Intervention: Patients were randomized to receive initial mechanical circulatory support with an Impella CPdevice.
  • Control: Patients were randomized to receive initial mechanical circulatory support with venoarterial ECMO (VA-ECMO).
  • Management Common to Both Groups: All patients were intended to receive early coronary revascularization (PCI) and best medical therapy for cardiogenic shock. Crossover to the other device was allowed as a rescue therapy.
  • Power and Sample Size: The authors calculated that a sample size of 298 patients would provide 80% power to detect a 15% absolute risk reduction in 30-day mortality. (Power is a study’s ability to find a real difference between treatments if one truly exists; 80% is the standard accepted level for clinical trials).
  • Outcomes:
    • Primary Outcome: All-cause mortality at 30 days.
    • Secondary Outcomes: Included a composite of death, stroke, or limb ischemia; duration of mechanical ventilation; and rates of bleeding and device-related complications.

6. Key Results

  • Enrollment and Baseline: 298 patients were randomized (148 to Impella and 150 to VA-ECMO). The groups were well-matched at baseline.
  • Trial Status: The trial was stopped early by the data and safety monitoring board for futility after an interim analysis showed no significant difference and a low probability of finding one.
  • Primary Outcome: There was no significant difference in 30-day mortality. 72 of 148 patients (48.6%) in the Impella group died, compared with 69 of 150 patients (46.0%) in the VA-ECMO group (p=0.64).
  • Secondary Outcomes: There were no significant differences between the groups in the composite secondary outcome.
  • Adverse Events: The incidence of moderate or severe bleeding and peripheral vascular complications was similar in both groups.

7. Medical Statistics

  • Analysis Principle: The trial was analyzed using an intention-to-treat principle.
  • Statistical Tests Used: The primary outcome was analyzed using a chi-square test.
  • Primary Outcome Analysis: The primary outcome was a comparison of the proportions of death between the two groups.
  • Key Statistic(s) Reported: Relative Risk (RR) for death at 30 days: 1.06 (95% CI, 0.82 to 1.36; P-value: 0.64).
  • Interpretation of Key Statistic(s):
    • Relative Risk (RR):
      • Formula: Conceptually, RR = (Risk in Intervention Group) / (Risk in Control Group).
      • Calculation: The paper reports the result as 1.06.
      • Clinical Meaning: An RR of 1.06 suggests a non-significant 6% higher relative risk of death in the Impella group.
    • Confidence Interval (CI):
      • Formula: Conceptually, CI = (Point Estimate) ± (Margin of Error).
      • Calculation: The 95% CI was 0.82 to 1.36.
      • Clinical Meaning: Since this range crosses the line of no effect (1.0), it confirms that the result is not statistically significant. Clinically, this means the true effect could range from an 18% benefit to a 36% harm.
    • P-value: The p-value of 0.64 is much higher than the 0.05 threshold, indicating the result is not statistically significant and very likely due to chance (a result is conventionally considered statistically significant if the p-value is less than 0.05).
  • Clinical Impact Measures: As the trial was neutral, ARR and NNT are not applicable.
  • Subgroup Analyses: No significant differences were found in any of the pre-specified subgroups.

8. Strengths of the Study

  • Study Design and Conduct: The multicenter, randomized, controlled design provided the first high-quality, head-to-head evidence on this critical clinical question.
  • Generalizability: The inclusion of 16 diverse, high-volume centers increases the applicability of the findings to similar settings.
  • Statistical Power: Although stopped early, the trial was large enough to confidently rule out a major benefit of one strategy over the other.
  • Patient-Centered Outcomes: The primary outcome of 30-day mortality is a robust and patient-centered endpoint.

9. Limitations and Weaknesses

  • Internal Validity (Bias): The study was open-label, which is an unavoidable limitation for this type of intervention and introduces a risk of performance bias.
  • External Validity (Generalizability): The trial was conducted in high-volume, expert centers in Germany. The high rate of complications and mortality in both arms might be even higher in less experienced centers.
  • Other: The trial was stopped early for futility, which means it was underpowered to definitively rule out a smaller, but still potentially important, treatment effect.

10. Conclusion of the Authors

  • The authors concluded that among patients with AMI and cardiogenic shock, an initial strategy of mechanical circulatory support with Impella CP was not superior to an initial strategy of VA-ECMO with regard to 30-day mortality.

11. To Summarize

  • Impact on Current Practice: This is a landmark trial that provides strong evidence that neither of the two most powerful forms of mechanical circulatory support is clearly superior to the other as an initial strategy in AMI-cardiogenic shock.
  • Specific Recommendations:
    • Patient Selection: For adult patients with AMI and cardiogenic shock.
    • Actionable Intervention: The results suggest that the choice between Impella and VA-ECMO as the initial device can be based on local expertise, patient-specific factors (e.g., presence of respiratory failure), and device availability, as there is no evidence of a survival difference.
  • What This Trial Does NOT Mean: This trial does NOT mean that mechanical circulatory support is not beneficial. It only compares two active strategies.
  • Implementation Caveats: The key takeaway is that despite the use of advanced mechanical support, mortality in cardiogenic shock remains extremely high. The focus must remain on rapid revascularization and excellent supportive care.

12. Context and Related Studies

  • Building on Previous Evidence: The PEERLESS trial (2024) was a direct follow-up to the IABP-SHOCK II trial (2012), which showed no benefit of IABP, and the ECLS-SHOCK trial (2023), which showed no benefit of routine early ECMO over medical therapy alone.
  • Influence on Subsequent Research: The definitive neutral finding of this trial will be highly influential in shaping future guidelines, suggesting that there is no single “best” device for all patients and reinforcing the need for an individualized approach.

13. Unresolved Questions & Future Directions

  • Unresolved Questions: The key unresolved question is how to best select which device is right for which patient. It is also unknown if a strategy of combining devices (e.g., ECMO plus Impella for LV venting) is superior to either device alone.
  • Future Directions: Future research will focus on identifying patient phenotypes that might respond better to one device over the other and on developing better strategies to mitigate the complications of mechanical circulatory support.

14. External Links

15. Framework for Critical Appraisal

  • Clinical Question: The research question was of the highest relevance, providing the first head-to-head comparison of the two leading advanced mechanical circulatory support devices for a devastating condition.
  • Methods: The multicenter RCT design was appropriate and robust. The main methodological weakness is the open-label design. The early termination for futility is a key point for interpretation.
  • Results: The study reported a clear neutral finding for its primary outcome, with a confidence interval that was centered on the null value. This provides strong evidence against a meaningful clinical benefit of one strategy over the other.
  • Conclusions and Applicability: The authors’ conclusion is a direct and fair reflection of the data. The high external validity of this pragmatic trial means its findings are broadly applicable to high-volume centers that use both devices. The trial is a classic example of a high-quality “negative” trial that is practice-changing by demonstrating the equivalence of two competing, complex, and expensive therapies.

16. Disclaimer and Contact

  • This summary is provided by the Academic Committee of ESBICM (ACE) to facilitate the understanding of this study; readers are advised to refer to the original trial document for a deeper understanding. If you find any information incorrect, or missing, or it needs an update or have a request for a specific critical care trial summary, kindly write to us at academics[at]esbicm.org.
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