Key result
Female sex was associated with a lower risk of incident myocarditis at 6 months compared to male sex following immune checkpoint inhibitor therapy (RR 0.76; 95% CI 0.63-0.91; P=0.004).
Why the study?
The impact of biological sex on immune checkpoint inhibitor-associated cardiotoxicity remains incompletely defined in real-world populations.
Does female sex reduce the risk of incident myocarditis and other cardiovascular immune-related adverse events compared to male sex in adults initiating immune checkpoint inhibitor therapy?
Cohort (n=120,232)
Yes
Does female sex reduce the risk of incident myocarditis and other cardiovascular immune-related adverse events compared to male sex in adults initiating immune checkpoint inhibitor therapy?
Answers are grounded in this paper and cite their sources.
Biological sex significantly influences the pattern of ICI-associated cardiotoxicity, with males at higher risk for myocarditis and arrhythmias, and females at higher risk for Takotsubo cardiomyopathy.
BACKGROUND: Immune checkpoint inhibitors (ICIs) are widely used in cancer therapy but may cause cardiovascular immune-related adverse events (irAEs) with substantial morbidity and mortality. The impact of biological sex on ICI-associated cardiotoxicity remains incompletely defined in real-world populations. OBJECTIVES: To evaluate sex-based differences in cardiovascular immune-related adverse events following immune checkpoint inhibitor therapy. METHODS: We conducted a retrospective, propensity score-matched cohort study using the TriNetX global research network. Adults initiating ICI therapy were stratified by biological sex and matched 1:1 on demographics, cardiovascular comorbidities, and baseline cardiotoxic therapies. The primary outcome was incident myocarditis at 6 months, 1 year, and 2 years. Secondary outcomes included arrhythmias, conduction abnormalities, and cardiomyopathies. Relative risks (RRs) with 95% confidence intervals (CIs) were reported. RESULTS: The matched cohort included 60,116 pairs of female and male patients with good overall covariate balance. Females had a lower risk of myocarditis at 6 months (RR 0.76; 95% CI 0.63-0.91; P=0.004), 1 year (RR 0.81; 95% CI 0.68-0.95; P=0.011), and 2 years (RR 0.81; 95% CI 0.69-0.94; P=0.008), along with lower risks of atrial fibrillation, ventricular arrhythmias, high-degree atrioventricular block, ischemic cardiomyopathy, and dilated cardiomyopathy. In contrast, females had a higher risk of Takotsubo cardiomyopathy across all time points. CONCLUSIONS: ICI-associated cardiotoxicity is associated with sex-related differences, with higher rates of myocarditis and arrhythmic events in males and increased occurrence of Takotsubo cardiomyopathy in females. These findings suggest differences in cardiovascular risk patterns and highlight the need for further study to better understand their clinical relevance.
No takes yet. Share an insight, caveat, or question.
Bahar et al. (2026) conducted a cohort in Cancer (initiating immune checkpoint inhibitor therapy) (n=120,232). Female sex vs. Male sex was evaluated on Incident myocarditis at 6 months (RR 0.76, 95% CI 0.63-0.91, p=0.004). Female sex was associated with a lower risk of incident myocarditis at 6 months compared to male sex following immune checkpoint inhibitor therapy (RR 0.76; 95% CI 0.63-0.91; P=0.004).
Synapse has enriched 8 closely related papers on similar clinical questions. Consider them for comparative context: