Sex differences in infarct–related cardiogenic shock: a secondary analysis of the ECLS–SHOCK trial

Background Women with infarct-related cardiogenic shock (AMI-CS) are underrepresented in randomised trials and may experience different clinical outcomes compared with men. Whether sex independently influences mortality in AMI-CS and whether treatment effects of extracorporeal life support (ECLS) differ by sex remain insufficiently defined. Purpose To investigate sex-specific differences in outcomes and treatment effects in patients with AMI-CS enrolled in the randomised ECLS-SHOCK trial. Methods This prespecified secondary analysis included 417 patients with AMI-CS randomised to early unselected ECLS plus usual medical treatment or usual medical treatment alone. The primary endpoint was 30-day all-cause mortality; the secondary endpoint was 12-month mortality. Hazard ratios (HRs) with 95% confidence intervals (CIs) were derived using multivariable Cox regression models adjusted for age, admission creatinine and lactate and multivessel coronary artery disease. Results Of 417 patients, 78 (18.7%) were women; median age was 63 years (IQR 56–70) in men and 65 years (IQR 58–72) in women (p=0.11). Women had lower serum creatinine (1.1 vs. 1.3 mg/dL; p<0.001), less multivessel disease (58.1% vs. 68.7%, p=0.005) and fewer prior percutaneous coronary interventions (7.8% vs. 19%, p=0.018). Lactate levels on admission were comparable. Revascularisation strategy and cannulation techniques were similar, whereas mechanical ventilation was less frequent in women (85.5% vs. 93.3%; p=0.025). Thirty-day mortality was higher in women (57.7% vs. 46.3%). Female sex was not significantly associated with the unadjusted 30-day mortality (HR 1.38, 95% CI 0.98–1.92), but after adjustment (adjusted HR 1.69, 95% CI 1.18–2.42). In women, 30-day mortality was 56.4% with ECLS versus 59.0% with usual care (p=0.82); in men, corresponding rates were 45.9% and 46.7% (p=0.87), respectively. No sex-by-treatment interaction was observed (p=0.89), indicating no evidence of a sex-specific treatment effect. At 12 months, all-cause mortality was 61.5% in women and 54.0% in men (Figure 1). Although the unadjusted association between female sex and 12-month mortality was not statistically significant (HR 1.28, 95% CI 0.93–1.75), female sex remained independently associated with mortality after multivariable adjustment (adjusted HR 1.52, 95% CI 1.08–2.14). Conclusion In this secondary analysis of ECLS-SHOCK, female sex was independently associated with higher 30-day and 12-month all-cause mortality after adjustment for baseline characteristics in patients with severe CS. The treatment effect of early ECLS did not differ by sex. These findings should be interpreted cautiously given the limited number of women (n=78) and the exclusion of 28 patients from adjusted analyses due to missing data.12-month all-cause mortality