Sex-specific excess long-term all-cause mortality among patients with a diagnosis of pulmonary embolism compared to matched control subjects from the general population

Background Patients with a diagnosis of pulmonary embolism (PE) have higher mortality than those without. However, whether the impact of a PE diagnosis on long-term all-cause mortality differs among men and women across age groups is scarcely studied. Purpose To assess the relative mortality risk among men and women with PE versus matched controls from the general population. Secondary aims included assessing mortality causes among men and women with and without PE. Methods Nationwide Swedish register study of all patients without cancer with a first-time diagnosis of PE and a subsequent anticoagulant prescription filling, from July 2005 to December 2019 and January 2022 to December 2023 (2020-2021 excluded due to the COVID-19 pandemic), and age-, sex- and area-of-residence-matched control subjects who were free of PE on the matching date. Multivariable Cox regression models, adjusted for patient characteristics and comorbidities, were used to estimate adjusted hazard ratios (aHRs) comparing cases to controls. Results A total of 49,353 patients and 49,353 controls were included; 52.1% were women. Men had a median age of 67 (range 18-100) years, and women 74 (18-103) years. Most comorbidities were more common among PE patients than control subjects, without sex differences. Dementia, systemic connective disorders, and lower extremity fractures were more common among women than men with PE. The mortality rate for men with PE was 4.51 (95% CI: 4.38-4.64) per 100 person-years, and 2.04 (95% CI: 1.95-2.12) for control subjects; aHR 1.88 (1.79-1.98). Corresponding numbers were 6.25 (6.10-6.40) per 100 person-years for women with PE and 3.15 (3.05-3.25) for controls; aHR 1.69 (1.62-1.76). A PE diagnosis had a higher relative association with mortality among men than women (p-value for interaction 0.0008). Sex differences in aHRs across age categories were mainly driven by low mortality rates among control subjects in younger age groups. Cardiovascular disease was the leading cause of mortality among patients and control subjects of both sexes. Fatal PE accounted for 5% of deaths among cases of both sexes. Conclusions Patients with PE who survived the initial hospitalization and filled a prescription of anticoagulants had substantially higher mortality than control subjects, with no clinically meaningful difference between men and women. Longterm mortality among patients with PE was driven by comorbidities rather than the direct effects of venous thromboembolism.