Abstract Body (Do not enter title and authors here): Background: Several studies have assessed sex differences in outcomes of patients with pulmonary embolism (PE). However, they have been limited by small sample sizes, lack of a prespecified protocol, or other methodological problems.

Aims: The SERIOUS-PE study was designed for rigorous prespecified analyses in patients aged ≥65 years, a group most likely to suffer from PE and its adverse outcomes.

Methods: We used data from the RIETE registry (predominantly representing Europe) and a validated algorithm using ICD-10 codes to identify US Medicare Fee-For-Service beneficiaries with PE. To focus on clinically-relevant differences in clinical characteristics, standardized differences (SRD)>10% were considered. Thirty-day outcomes were assessed in unadjusted and adjusted models.

Results: The outcomes analysis included 33,462 patients from RIETE (age 77.6 years, 59.5% female) and 666,128 from Medicare (age 73.5 years, 53.9% female). Females were older than males (SRD: 34% [RIETE] and 30% [Medicare]), and more frequently had varicose veins, immobility, depression, or hormonal therapy (SRD>10%). Males more frequently had atherosclerotic diseases and cancer (SRD>10%). Thrombus burden, PE risk stratification, anticoagulant therapy, and advanced therapies did not have clinically-relevant differences between groups (SRD<5%). 30-day mortality occurred in 6.4% of females and 6.8% of males in RIETE (OR 0.91, 95% CI 0.83-1.00) and 15.2% of females and 16.5% of males in Medicare (OR 0.91, 95% CI 0.90-0.92). After adjusting for age and other covariates, females had a higher risk of mortality than males in RIETE (aOR 1.24, 95% CI 1.11-1.39) and in Medicare (aOR 1.10, 95% CI 1.08-1.13). 30-day readmission occurred in 14.7% of females and 15.1% of males in Medicare (OR 0.97, 95% CI 0.96-0.99, and aOR 1.00, 95% CI 0.98-1.01).

Conclusions: This is the most comprehensive assessment of sex differences in presentation, treatment strategies, and outcomes of older adults with PE. Sex differences in crude vs adjusted mortality warrant additional investigation.