https://orcid.org/0000-0002-1349-9969
Introduction
In the treatment of cardiogenic shock related to acute myocardial infarction (AMI-CS), extracorporeal life support (ECLS) has surged more than tenfold over the past decade.1 However, recent randomised controlled trials (RCTs) and an individual patient data meta-analysis have demonstrated that early, non-selective ECLS use does not improve short-term survival compared to medical therapy alone.2–5 Conversely, patients treated with ECLS experienced more complications including moderate to severe bleeding and peripheral vascular complications necessitating intervention. In light of the recently published Danish German Cardiogenic Shock (DanGer Shock) trial which showed a mortality benefit at 6 months for a microaxial flow pump, longer-term follow-up is necessary to comprehensively capture the spectrum of potential differential effects associated with the use of mechanical circulatory support (MCS).6 In this context, we present 1-year results of the ECLS-SHOCK (Extracorporeal Life Support in Cardiogenic Shock) trial, the largest RCT of ECLS treatment in AMI-CS to date.
Methods
The ECLS-SHOCK trial is an investigator-initiated, randomised, international, multicentre, open-label trial with the primary objective to examine whether early routine ECLS in addition to usual medical treatment improves survival in patients with CS complicating AMI with planned revascularisation compared to usual medical care alone. The design of the trial and 30-day outcomes have been published previously.4,7
For the 1-year outcomes, the following prespecified secondary endpoints are reported: all-cause and cardiovascular mortality, neurological status (cerebral performance category), recurrent myocardial infarction, need for repeat revascularisation, and rehospitalisation for heart failure. In addition, quality of life in survivors was assessed using the EuroQoL-5D-3L questionnaire.8
Results
Between June 2019 and November 2022, a total of 420 patients with AMI-CS were randomly assigned to ECLS or standard medical care at 44 trial sites. Three patients who did not provide informed consent were subsequently excluded, resulting in a final population of 417 patients for analysis (Figure 1A). Baseline and treatment characteristics of the patients have been published previously.4 Of note, more than three quarters of the overall population (77.7%) had been resuscitated before enrolment. Routine ECLS provided no benefit over usual medical care alone with respect to the primary endpoint of 30-day risk of death from any cause. The secondary safety endpoints of moderate or severe bleeding and peripheral vascular complications warranting intervention occurred significantly more frequently in patients allocated to the ECLS group.
Clinical outcomes at 1 year. AMI-CS, cardiogenic shock related to acute myocardial infarction; CI, confidence interval; CPC, cerebral performance category; ECLS, extracorporeal life support; HR, hazard ratio; RR, relative risk
At 1 year, all-cause mortality was 55.0% (115/209) in the ECLS group and 55.8% (116/208) in the control group without significant difference between the treatment strategies (Figure 1B). These results were consistent across all subgroups (sex, age < 65 vs. ≥65 years, ST-segment elevation vs. non-ST-segment elevation AMI, anterior vs. non-anterior ST-segment elevation AMI, lactate levels ≤ 6 vs. >6 mmol/L, diabetes vs. no diabetes, and cardiopulmonary resuscitation vs. no resuscitation before enrolment). In the surviving patients, the rates of severe neurological deficit, myocardial reinfarction, repeat revascularisation, and rehospitalisation for heart failure were similar at 1 year (Figure 1D). A post hoc landmark analysis (30 days to 1 year) revealed that mortality rates after the first month were markedly lower than in the first 30 days (Figure 1C). There was no difference in all-cause mortality between the treatment groups in the time period between 30 days and 1 year (hazard ratio 1.07; 95% confidence interval 0.52–2.21). The overall quality of life among the 143 survivors showed no significant differences between the groups across most dimensions (Figure 1E). However, patients who had undergone ECLS reported a higher rate of pain or discomfort (P = .013).
Discussion
The 1-year results of the ECLS-SHOCK trial corroborate previous short-term data from RCTs and an individual patient data meta-analysis of RCTs indicating no substantial survival benefit of routine ECLS over conventional medical therapy alone in the management of infarct-related CS.2–5,9 Moreover, this study revealed no significant differences in secondary endpoints, such as neurological outcome, myocardial reinfarction, need for repeat revascularisation, or rehospitalisation for heart failure between groups.
The absence of a mid-term survival benefit raises critical questions about the role of ECLS in the management of AMI-CS. While ECLS may provide immediate haemodynamic stabilisation and support, its use is accompanied by a higher incidence of adverse events, notably bleeding and vascular complications. A noteworthy aspect of the findings is the quality-of-life assessment. Most quality-of-life scores were similar between groups. However, patients who underwent ECLS reported a higher incidence of pain and discomfort at the 1-year mark. This experience of increased discomfort underscores the physical burden associated with ECLS, which may detract from its perceived benefits.
As opposed to the ECLS-SHOCK trial, the DanGer Shock trial showed a survival benefit at 6 months using a microaxial flow pump in patients with AMI-CS. Major differences between the two trials are the use of differing MCS devices and stricter inclusion criteria in DanGer-Shock, which only enrolled patients with ST-segment elevation AMI-CS without apparent risk of hypoxic brain injury.
The trial has limitations. First, the heterogeneity of patients with AMI-CS suggests that ECLS might have conferred long-term benefits to specific subgroups, although such an effect was not observed in any of the subgroups analysed. The high rate of patients with resuscitation prior to inclusion deserves particular consideration as these might not be ideal candidates for ECLS due to frequent severe hypoxic brain injury. Second, while the study provides valuable 1-year follow-up data, longer-term outcomes remain unknown. Third, the ECLS-SHOCK trial studied the routine use of ECLS in AMI-CS. The results should therefore not be transferred to non-infarct-related causes of CS or other shock forms in general. In addition, patients with refractory cardiac arrest and ongoing cardiopulmonary resuscitation were excluded. Fourth, blinding of the intervention was not possible, which may have impacted therapeutic decisions of healthcare providers. Fifth, 27.9% of the patients in the control group actually received MCS, which may potentially dilute the study’s interpretation.
In conclusion, the ECLS-SHOCK trial provides robust evidence that routine ECLS does not improve 1-year survival in patients with AMI-CS undergoing planned revascularisation. Other forms of MCS and—probably more important—strict patient selection excluding patients with risk of hypoxic brain injury may offer advantages as recently demonstrated with a microaxial flow pump after 6 months.6,10
Declarations
Disclosure of Interest
U.Z. reports payment or honoraria for lectures from Ferrer, Astra Zeneca, Zoll, Bayer, BMS, Pfizer, Boehringer Ingelheim, Getinge, Xenios, Chiesi, Idorsia, and Novartis. D.D. reports payment or honoraria for lectures from Daiichi Sankyo, Pfizer, Boehringer Ingelheim, Astra Zeneca, Bayer Healthcare, and AOP Healthcare; he reports support for attending meetings and/or travel from Bayer Healthcare and Daiichi Sankyo; he reports participation on a data safety monitoring board or advisory board for Johnson & Johnson and CSL Behring. T.R. reports a grant from the German Research Foundation; he reports payment for lectures from Astra Zeneca, Bayer, Daiichi Sankyo, CVRx, BMS, and Novartis; he reports support for attending meetings and/or travel from the German Cardiac Society; he reports several patents; he is a co-founder of Bimyo GmbH. I.E. reports grants from the European Union, Novartis, the German Center for Cardiovascular Research (DZHK), Abbott, and Meril; he reports payment or honoraria for lectures from Alnylam, Alleviant, Abbott Vascular, Astra Zeneca, Bayer, Biotronik, Boston Scientific, Boehringer Ingelheim, Bristol Myers Squibb/Pfizer, Corvia, Daiichi Sankyo, Edwards Lifesciences, Janssen, Meril, Novartis, Pharmacosmos, and Sanofi; he reports support for attending meetings and/or travel from Meril, Novartis, and Alleviant. T.S. reports consulting fees from Myocardia and Bristol Myers Squibb; he reports payment or honoraria for lectures from Abbott Vascular, Astra Zeneca, Boehringer Ingelheim, Bristol Myers Squibb, Corvia, Edwards Lifesciences, Medtronic, Myocardia, Novartis, and Pfizer; he reports payment for expert testimony from Bristol Myers Squibb; he reports support for attending meetings and/or travel from Teleflex; he reports participation on a data safety monitoring board or advisory board for Myocardia and Bristol Myers Squibb. P.C. reports participation on a data safety monitoring board or advisory board and holds stock or stock options for Novo Nordisk and Johnson & Johnson. S.E. reports consulting fees from Medtronic, Recor, and Inari Medical; he reports payment or honoraria for lectures from Akcea Therapeutics, Astra Zeneca, Bayer, Berlin Chemie, Bristol Myers Squibb/Pfizer, Boehringer Ingelheim, Daiichi Sankyo, Edwards Lifesciences, Inari Medical, Kaneka Pharma, Medtronic, Neovasc, Novartis, and Recor; he reports support for attending meetings and/or travel from Daiichi Sankyo, Bristol Myers Squibb/Pfizer, Astra Zeneca, and Bayer. E.T. reports grants and consulting fees from Medtronic and Boston Scientific; he reports payment or honoraria for lectures from Medtronic, Abiomed, and Resuscitec; he reports support for attending meetings and/or travel from Medtronic, Abiomed, and Edwards; he reports leadership or fiduciary role in the German Cardiac Society and the German Resuscitation Council. C.J. reports grants from the German Research Foundation, German Ministry for Economy and Energy, State of Nordrhine-Westfalia, German Space Agency, European Union, and Edwards Lifesciences; he reports payment or honoraria for lectures from Bristol Myers Squibb, Daiichi Sankyo, and Boehringer Ingelheim; he reports unpaid leadership or fiduciary role in the German Cardiac Society, German Society for Internal Medicine, German Society for Medical Intensive Care, and the European Society for Intensive Care Medicine. J.P. reports grants from the German Cardiac Society, the German Heart Research Foundation, the Dr. Rolf M. Schwiete Foundation, and Maquet Cardiopulmonary GmbH; she reports support for attending meetings and/or travel from Overcome GmbH; she reports unpaid leadership or fiduciary role in the ESC-ACVC. T.O. reports support for the present manuscript from the Helios Health Institute. S.D. reports support for the present manuscript from the Helios Health Institute. A.F. reports support for the present manuscript from the German Heart Research Foundation.
Data Availability
The data underlying this article cannot be shared publicly due to privacy reasons. The data will be shared on reasonable request to the corresponding authors.
Funding
The trial was supported by the Else Kröner Fresenius Foundation, the German Heart Research Foundation, and the Helios Health Institute.
Ethical Approval
Ethics committees of all participating centres approved the trial.
Pre-registered Clinical Trial Number
The pre-registered clinical trial number is www.ClinicalTrials.gov: NCT03637205.
References
Author notes
Steffen Desch and Uwe Zeymer should both be considered as first authors.
Anne Freund and Holger Thiele should both be considered as senior authors.
