Out-of-hospital cardiac arrest (OHCA) is a major public health concern worldwide with high occurrence and mortality rates (1–3). In Japan, there are approximately 70,000 cases of OHCA annually (4, 5). The incidence of emergency medical services (EMS)-treated OHCA in the United States is estimated to be 356,461, with nearly 90% of the cases being fatal (6). The overall prognosis and neurological outcomes are relatively poor following OHCA, and survival to hospital discharge after EMS-treated cardiac arrest is approximately 10% (1–6). The American Heart Association-International Liaison Committee on Resuscitation advocates the “chain of survival” model, which emphasizes the need for timely access to medical care and early intervention (7). Moreover, the guidelines address sex-related inequalities, with female victims less likely to receive bystander cardiopulmonary resuscitation (CPR), which is a major issue (7).

In recent years, there has been growing interest in examining the differences in the prognosis of various diseases between men and women (8–13). Research has found sex-related disparities in pathophysiology, clinical symptoms, and outcomes, as well as in medical care received (8–13). Cardiovascular disease is the most extensively analyzed topic of sex-related differences. Studies have shown that there is a variation in clinical outcomes after percutaneous coronary intervention (PCI) for acute myocardial infarction between sexes (14). Women appear to have a greater risk of heart failure following PCI for acute myocardial infarction than men, despite having the same technical success rate (15). Studies also suggest that women are less likely to receive mechanical cardiac support or undergo diagnostic procedures such as coronary angiography or PCI (16). Researchers have conducted multiple studies on possible sex differences associated with OHCA prognosis; however, their findings have been inconsistent (17, 18). Whether sex-based variations affect the prognosis of OHCA is unclear.

The treatment of OHCA in hospitals has seen a surge in specialized interventions, such as extracorporeal cardiopulmonary resuscitation (ECPR), targeted temperature management (TTM), and PCI, making them standard protocols globally (19, 20). Despite these advances, research on sex-related differences in in-hospital treatment and post-resuscitation care is lacking. Studies conducted in Japan indicate that women aged 18–64 years are less likely to receive CPR in public, and men are more likely to receive aggressive prehospital treatment (21, 22). Therefore, we hypothesized that women in Japan receive fewer in-hospital treatments or have poorer survival outcomes than men. This study aimed to explore sex-associated differences in in-hospital treatment and survival outcomes in Japan using the JAAM-OHCA registry, a multicenter prospective database.

A flow chart of the patient selection process is shown in Figure 1. During the study period, 68,110 OHCA cases were documented in the JAAM-OHCA registry. Among them, 5,296 adult patients (4,270 men and 1,026 women) with shockable rhythms at the scene were eligible for analysis.

Table 1 shows patient characteristics according to sex. Women were older and less likely to have coronary disease than men. A higher proportion of OHCA cases was observed in men than in women. The proportion of women who received shock from both a public AED and bystander-initiated chest compression or had an ROSC status was similar to that of men. Men were more likely to receive prehospital adrenaline administration and sustain VF/pulseless VT rhythm at hospital arrival than women. The time from call to hospital arrival was longer in men than in women.

Sex disparities in outcomes are shown in Table 2. Overall, 37.4% of women (384 of 1,026) and 39.5% of men (1,685 of 4,270) had 1-month survival (crude odds ratio [OR], 0.92; 95% CI: 0.80–1.06). In the multivariate logistic regression analyses, the outcome tended to be better in women than in men (AOR: 1.30; 95% CI: 0.81–2.09 after adjusting for only prehospital factors) (AOR: 1.38; 95% CI: 0.82–2.33 after adjusting for both prehospital and in-hospital factors), although it was not significantly different. In cases of 1-month survival with favorable neurological outcomes, the results were similar.

Sex disparities in in-hospital treatment are shown in Table 3. With a focus on highly specialized interventions, 13.0% of women (133 of 1,026) and 22.0% of men (939 of 4,270) received ECPR (crude OR: 0.53; 95% CI: 0.43–0.64). In contrast, there was no significant difference between the sexes in terms of those who received ECPR (AOR, 0.81; 95% CI, 0.49–1.33) in the multivariate logistic regression analyses. Similarly, the number of male patients who received TTM was 1,533 (35.9%), whereas the number of female patients who received TTM was 302 (29.4%) (crude OR: 0.74; 95% CI: 0.64–0.86; AOR: 0.99; 95% CI: 0.68–1.46).

In the subgroup analysis focused on ST-segment elevation in 12-lead ECG after ROSC, in cases with VF/pulseless VT as the first documented rhythm at hospital arrival and in ROSC after/at hospital arrival, women were almost equally likely to receive in-hospital treatment when compared with men (Table 4).

In this study, we evaluated the association between sex and survival outcomes of patients with OHCA with shockable rhythm at the scene or during in-hospital interventions using the JAAM-OHCA nationwide registry. There were no significant differences between women and men in terms of survival outcomes or hospital interventions, and this result was consistent in the subgroup analysis.

Several studies have examined the potential effect of sex on outcomes associated with OHCA and have reported varying results (17, 18, 29, 30). Some studies found no disparity between male and female survival rates following OHCA, whereas others found a survival advantage in males over females (30). According to a recent meta-analysis (31), women continue to exhibit substantially lower discharge survival rates and poorer neurological prognoses than men. Our findings, however, did not align with this conclusion, showing no statistically significant difference in survival outcomes between sexes. As noted in the meta-analysis, differences in medical care received after admission may play a role in the observed differences between male and female survival rates and should be considered when interpreting results from individual studies that do not account for this in-hospital factor adjustment. Furthermore, previous research conducted on sex-related differences in OHCA has shown significant variance in terms of the study participants' baseline characteristics and design, as a considerable proportion of patients with OHCA present with non-VF rhythm (31). This heterogeneity is a major bias in determining the sex-related differences described above. Hence, the outcomes of studies on sex-related disparity may not be as credible when combined or generalized because of selection and information bias. To simplify the diverse study design and baseline data, our study concentrated on sex differences in patients with OHCA with a shockable rhythm at the scene.

Our study showed that women tended to have better survival rates after adjusting for cardiac arrest. This OR reversal was also found in previous OHCA studies (32–34). Various factors, such as age, witnessed arrest, and bystander CPR, are associated with favorable outcomes in male patients with OHCA. Men also commonly experience an arrest of cardiac etiology and shockable rhythm as their initial cardiac rhythm, whereas women are more likely to have noncardiac etiologies (31). Consistent with this, the crude OR for survival outcome was also lower in women than in men in our study. However, after adjusting for prognostic factors, this analysis identified that survival outcomes tended to be better in women than in men. Therefore, we speculate that prehospital baseline factors and in-hospital care significantly affect OHCA survival rates between sexes, and previous studies may not have considered these factors, resulting in inconsistent findings. Contrary to our findings, a previous study conducted in the United States between 2003 and 2012 demonstrated that women had a higher risk of adjusted in-hospital mortality than men, particularly when diagnosed with VT/VF arrests (18). This could be due to the absence of prehospital information, interventions, or early in-hospital care in their research.

Reports have indicated varying rates of prevalence in channelopathies among different sexes (35). For instance, congenital long-QT syndrome has a higher predilection for women compared to men, putting women at a greater risk for Torsades de pointes and sudden cardiac death (36). Conversely, Brugada syndrome primarily affects adult men, who face a significantly elevated risk of arrhythmic, sudden cardiac death compared to women (37). This aspect holds significance for cardiomyopathies as well (38). Additionally, disparities in clinical characteristics may stem from societal and environmental factors that disadvantage women. According to previous reports, men tend to receive more post-admission interventions such as PCI, CAG, and TTM than women (39–41). Factors such as education level, religious beliefs, and economic level also contribute to women being more inclined to issue “do-not-resuscitate” instructions during OHCA, opting for more conservative treatment (42). One reason for this sex-related disparity might be that these treatments are invasive or expensive (43). Post-resuscitation care may also vary based on factors such as families' requests and professional concerns (17, 44). In contrast, our findings showed no significant difference in in-hospital treatment between the sexes. Furthermore, Japan's insurance system ensures that early cessation of expensive care for socioeconomic reasons is somewhat lower than that in other countries (45).

In our study, we showed that patients with OHCA with shockable rhythm who should be provided with highly specialized interventions have no sex-related disparity in survival outcomes or in-hospital treatment. Most previous studies have adjusted only for prehospital factors in patients with OHCA; thus, studies adjusted for in-hospital treatments such as care for post-cardiac arrest status are limited (31). Therefore, these results are considered appropriate. Our findings provide insights into sex-related disparities in patients with OHCA.

This study had some limitations. First, the Utstein style registry does not contain information on medications, medical history, and daily activities of each patient before cardiac arrest, which could affect the decision to pursue aggressive treatment options. Second, the registry does not provide detailed information on factors such as cardiovascular risk, symptom onset, and time to cardiac arrest, which might have skewed the results. Other potential factors, such as education level and sex inequality, may also play a role. Another limitation is the applicability of the study; as it is a single-country study, it would be intriguing to observe whether these findings hold true in a multinational study involving diverse patient populations and healthcare systems. Further investigations are required to confirm these findings and assess their generalizability.

In conclusion, using a prospective, nationwide, multicenter, OHCA registry in Japan, we focused on sex-related differences in patients with OHCA with shockable rhythm at the scene. After adjusting for prognostic factors, we found no difference in the survival rates or hospital interventions between men and women.