The treatment effect of venoarterial extracorporeal membrane oxygenation (VA-ECMO) remained neutral across the full spectrum of cardiopulmonary resuscitation (CPR) rates in the ECLS-SHOCK trial, a new reanalysis of the trial data suggests. The analysis, published online in JACC: Advances, addresses whether the high proportion of resuscitated patients in ECLS-SHOCK, 77% of whom underwent CPR before randomization, may have obscured a potential survival benefit of VA-ECMO in acute myocardial infarction complicated by cardiogenic shock. Led by Tharusan Thevathasan, MD, from the German Center for Cardiovascular Research and Deutsches Herzzentrum der Charité, Berlin, the researchers applied analytic mixture and bootstrap resampling approaches to simulate trial populations with varying CPR proportions ranging from 0% to 100%. "Varying the proportion of resuscitated patients did not materially change the estimated treatment effect of VA-ECMO. These findings suggest that CPR prevalence alone is unlikely to explain the neutral result of ECLS-SHOCK," the authors wrote, noting that given the post hoc and theoretical nature of the analysis, these results should be interpreted as hypothesis-generating. Across both analytical approaches, the estimated treatment effects consistently showed no survival advantage of VA-ECMO over control, reinforcing the original trial's neutral finding, they added. Study details Thevathasan and colleagues used data from the ECLS-SHOCK trial, with 30-day and 1-year all-cause mortality as primary outcomes. Treatment effects of VA-ECMO versus control were first estimated separately for patients with and without preceding CPR using logistic regression. In the analytic mixture approach, subgroup-specific odds ratios (ORs) for resuscitated and nonresuscitated patients were mathematically combined in varying proportions to generate hypothetical trial populations with CPR prevalence ranging from 0% to 100% in 10% increments, the investigators reported. In the resampling approach, synthetic trial cohorts of 420 patients were repeatedly generated at different CPR proportions, with ORs estimated across 1,000 iterations per scenario, according to the researchers. In patients with CPR, the OR for 30-day mortality with VA-ECMO versus control was 1.0 (95% CI: 0.65-1.55), the authors said. In patients without CPR, the corresponding OR was 0.81 (95% CI: 0.36-1.82). When the proportion of resuscitated patients was lower, the estimated OR shifted toward potential benefit with VA-ECMO (OR: 0.7-0.8), but confidence intervals consistently spanned unity, the investigators noted. Analyses of 1-year mortality outcomes yielded similar results, according to Thevathasan and colleagues. No interaction The original ECLS-SHOCK trial showed no survival benefit of VA-ECMO in patients with acute myocardial infarction complicated by cardiogenic shock, with 77% of enrolled patients having undergone CPR, the authors wrote, adding that the high resuscitation rate has been cited as potentially diluting a VA-ECMO treatment effect. By contrast, the team noted that the DanGer Shock trial excluded comatose CPR patients and enrolled only 20% resuscitated patients, all of whom were noncomatose, the investigators wrote. That trial demonstrated a mortality benefit with microaxial flow pumps, fueling speculation that CPR accounted for differing results between the trials. A prior prespecified subanalysis of ECLS-SHOCK compared outcomes between patients with and without CPR and found no significant interaction between resuscitation status and VA-ECMO treatment effect, according to the researchers. The absence of a statistically significant interaction effect underscores that the neutral overall finding is unlikely to be explained by CPR prevalence alone, they wrote. Other differences between the trials, including the devices themselves, stricter patient selection, timing of mechanical circulatory support initiation, and a notable 12% mortality increase from 30 days to 6 months in the DanGer Shock control group, may explain some outcome differences, the authors noted. Source: Thevathasan T, Zeymer U, Freund A, et al. Impact of varying resuscitation proportions of resuscitated patients on VA-ECMO outcomes in the ECLS-SHOCK trial. JACC Adv. 2026;5(3):102585. Image Credit: DJ Creative Studio – stock.adobe.com