Sex specific outcomes in patients with out-of-hospital cardiac arrest without ST-segment elevation - a substudy of the randomised TOMAHAWK trial

Abstract Background Out-of-hospital cardiac arrest (OHCA) is frequently caused by acute myocardial infarction, even in the absence of ST-segment elevation. Randomised controlled trials including the TOMAHAWK (Angiography after Out-of-Hospital Cardiac Arrest without ST-Segment Elevation) trial did not show superiority of immediate over delayed/selective coronary angiography (CAG) in these patients, despite a presumed cardiac arrest trigger. However, male and female OHCA patients often differ in terms of the baseline situation and clinical course. Purpose To evaluate sex specific differences in presentation and outcomes in patients with OHCA of possible cardiac origin but without ST-segment elevation randomised to either immediate CAG or a delayed/selective approach. Methods All patients of the randomised TOMAHAWK trial were stratified by sex. The primary outcome was 30-day all-cause mortality. Secondary outcomes included severe neurological deficit, stroke, myocardial infarction, acute renal failure requiring renal replacement therapy and major bleeding within 30 days, among others. Results Of the 530 patients analysed in the trial, 161 were female and 369 were male. A total of 80 females and 185 males were randomised to immediate coronary angiography after hospital admission. All others were planned to undergo CAG after 24 hours the earliest or no CAG at all. Male patients were more likely to have known coronary artery disease and a shockable first rhythm. Overall, CAG was performed in 119 (73.9%) of female and in 299 (81.0%) of male patients. Of the female patients only 48.3% had significant coronary artery disease, compared to 72.0% of males (p0.001). Subsequently, percutaneous coronary intervention (PCI) was performed less often in females compared to males (31.4% versus 42.9%, p=0.04). All-cause death at 30 days occurred in 87 female patients and in 180 male patients (56.1% versus 50.4%, p=0.29 for log-rank test) (Figure 1). No difference was seen with respect to secondary outcomes. In females, randomisation to immediate CAG was associated with a higher risk of death compared to delayed/selective CAG (41.3% versus 55.6%, p=0.021 by log-rank test) (Figure 2a). In males, no difference in the probability of survival was found between treatment groups. (49.7% versus 53.8%, p=0.43 by log-rank test) (Figure 2b). The p for interaction was 0.148, with a hazard ratio of 1.46 (95% confidence interval 0.87-2.45), indicating no statistically significant interaction between sex and treatment strategy on mortality. Conclusion In patients with OHCA of presumed cardiac origin and no ST-segment elevation, overall outcomes of male and female patients were comparable. However, female patients randomised to immediate CAG had worse 30-day all-cause mortality compared to delayed/selective CAG.