ECLS-SHOCK: ECMO in Myocardial Infarction with Cardiogenic Shock (2023)

“Among patients with acute myocardial infarction complicated by cardiogenic shock, early initiation of extracorporeal life support did not reduce the risk of death at 30 days as compared with early and complete revascularization.”

  • The ECLS-SHOCK Trial Investigators

1. Publication Details

  • Trial Title: Extracorporeal Life Support in Infarct-Related Cardiogenic Shock
  • Citation: Thiele H, Zeymer U, Akin I, et al. Extracorporeal Life Support in Infarct-Related Cardiogenic Shock. N Engl J Med. 2023;389(14):1286-1297. DOI: 10.1056/NEJMoa2307227
  • Published: October 5, 2023, in The New England Journal of Medicine
  • Author: Holger Thiele, M.D.
  • Funding: German Heart Research Foundation; German Research Foundation; and others.

2. Keywords

  • Myocardial Infarction, Cardiogenic Shock, Extracorporeal Life Support (ECLS), 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 extracorporeal life support (ECLS) plus standard medical therapy (Intervention) compared to standard medical therapy alone (Comparison) reduce 30-day all-cause mortality (Outcome)?

4. Background and Rationale

  • Existing Knowledge: Cardiogenic shock complicating AMI has a very high mortality rate, often exceeding 40%, despite early revascularization with PCI. Venoarterial extracorporeal membrane oxygenation (VA-ECMO), also known as ECLS, can provide temporary circulatory support and was being used with increasing frequency as a rescue therapy, based on observational data.
  • Knowledge Gap: Despite its physiological appeal and increasing use, there was no high-quality evidence from a large randomized controlled trial to determine if the routine, early initiation of ECLS improved survival in this high-risk population.
  • Proposed Hypothesis: The authors hypothesized that a strategy of early ECLS would be superior to standard medical therapy alone in reducing 30-day mortality.

5. Study Design and Methods

  • Design: A multicenter, prospective, open-label, randomized, controlled trial (used to test the effectiveness of interventions).
  • Setting: 44 centers in Germany and Slovenia.
  • Trial Period: Enrollment ran from June 2019 to February 2023.
  • Population:
    • Inclusion Criteria: Adult patients with AMI complicated by cardiogenic shock, for whom early revascularization was planned.
    • Exclusion Criteria: Included unwitnessed cardiac arrest with a duration >5 minutes without bystander CPR, severe peripheral artery disease precluding ECLS cannulation, and a terminal illness with life expectancy <6 months.
  • Intervention: Patients were randomized to receive immediate ECLS in addition to standard medical therapy.
  • Control: Patients were randomized to receive standard medical therapy alone, with the option for crossover to ECLS only as a rescue therapy in cases of refractory shock or cardiac arrest.
  • Management Common to Both Groups: All patients were intended to receive early and complete coronary revascularization (usually with PCI) and best medical therapy for cardiogenic shock.
  • Power and Sample Size: The authors calculated that a sample size of 420 patients would provide 80% power to detect a 12% 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 time to hemodynamic stabilization, duration of vasopressor support, and the incidence of complications such as severe bleeding and stroke.

6. Key Results

  • Enrollment and Baseline: 420 patients were randomized (211 to ECLS and 209 to control). The groups were well-matched at baseline.
  • Trial Status: The trial was completed as planned.
  • Primary Outcome: There was no significant difference in 30-day mortality. 100 of 209 patients (47.8%) in the ECLS group died, compared with 98 of 208 patients (47.1%) in the control group (p=0.89).
  • Secondary Outcomes: There were no significant differences between the groups in the time to hemodynamic stabilization or the duration of vasopressor support.
  • Adverse Events: The incidence of moderate or severe bleeding and peripheral vascular complications requiring intervention was significantly higher in the ECLS group.

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: 1.02 (95% CI, 0.83 to 1.25; P-value: 0.89).
  • 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 1.02.
      • Clinical Meaning: An RR of 1.02 suggests a non-significant 2% higher relative risk of death in the ECLS group.
    • Confidence Interval (CI):
      • Formula: Conceptually, CI = (Point Estimate) ± (Margin of Error).
      • Calculation: The 95% CI was 0.83 to 1.25.
      • 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 a 17% benefit to a 25% harm.
    • P-value: The p-value of 0.89 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 high-quality evidence on a critical clinical question.
  • Generalizability: The inclusion of 44 diverse centers increases the applicability of the findings.
  • Statistical Power: The study was adequately powered for its primary outcome.
  • 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 (unblinded), 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 Europe. The high rate of complications in the ECLS arm might be even higher in less experienced centers.
  • Other: A significant proportion of patients in the control group (12.4%) crossed over to receive rescue ECLS, which could have diluted the difference between the groups, biasing the result towards the null.

10. Conclusion of the Authors

  • The authors concluded that in patients with acute myocardial infarction and cardiogenic shock, the early routine use of ECLS did not reduce 30-day mortality as compared with standard medical therapy alone.

11. To Summarize

  • Impact on Current Practice: This was a landmark, practice-changing trial that provided strong evidence to argue against the routine, prophylactic use of ECLS in all patients with AMI-cardiogenic shock.
  • Specific Recommendations:
    • Patient Selection: For the broad population of adult patients with AMI-cardiogenic shock.
    • Actionable Intervention: The results do not support the routine, early initiation of ECLS in all patients.
  • What This Trial Does NOT Mean: This trial does NOT mean that ECLS should never be used. It remains a potential life-saving rescue therapy for patients with refractory shock or cardiac arrest who have failed all other therapies.
  • Implementation Caveats: The findings highlight the significant risks associated with ECLS, including bleeding and vascular complications, which must be weighed against the unproven benefit when considering its use.

12. Context and Related Studies

  • Building on Previous Evidence: The ECLS-SHOCK trial (2023) was the first large, multicenter RCT to provide high-quality evidence on a practice that was rapidly expanding based on observational data and physiological rationale.
  • Influence on Subsequent Research: The definitive neutral-to-harmful result of this trial will be highly influential in shaping future guidelines and will likely temper the enthusiasm for routine, early ECLS, shifting its role back to a more selective, rescue therapy.

13. Unresolved Questions & Future Directions

  • Unresolved Questions: The key unresolved question is how to best select the specific patients who are most likely to benefit from ECLS as a rescue therapy.
  • Future Directions: Future research will focus on identifying predictors of success with ECLS and on comparing ECLS to other forms of mechanical circulatory support.

14. External Links

15. Framework for Critical Appraisal

  • Clinical Question: The research question was highly relevant, addressing a high-stakes intervention for one of the deadliest conditions in critical care cardiology.
  • Methods: The multicenter RCT design was appropriate and robust. The main methodological weakness is the open-label design. The significant crossover rate from the control to the ECLS arm is a key point for interpretation and may have biased the result towards finding no difference.
  • Results: The study reported a clear neutral finding for its primary outcome. The finding of a significant increase in bleeding and vascular complications in the ECLS group is a critical safety signal.
  • Conclusions and Applicability: The authors’ conclusion is a direct and fair reflection of the data. The trial provides strong evidence to discourage the routine, prophylactic use of ECLS in all patients with AMI-cardiogenic shock and reinforces its role as a selective rescue therapy.

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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