Study Background and Disease Burden
Pulmonary embolism (PE) represents a significant global health challenge, contributing substantially to cardiovascular morbidity and mortality worldwide. Despite improvements in diagnostic methodologies and therapeutic options, PE-related mortality remains a major concern, especially given its rapid clinical progression and frequent underdiagnosis. Understanding international trends in mortality related to PE is crucial for guiding public health strategies and resource allocation. However, previous studies have not adequately explored how mortality rates vary across regions with diverse economic statuses and healthcare capabilities. This epidemiological study undertook a comprehensive global analysis to elucidate long-term patterns in PE-related mortality and identify disparities influenced by geographic, economic, and healthcare factors.
Study Design
This study analysed mortality registration data from the World Health Organization Mortality Database, spanning 2001 to 2023, updated as recently as February 2025. Pulmonary embolism-related deaths were identified using specific International Statistical Classification of Diseases and Related Health Problems, Tenth Revision (ICD-10) codes: I26 for acute PE, and additional codes (I80, I822, I828, I829, O882, O222, O223, O229, O870, O871, O879) covering venous thromboembolism forms. To ensure data consistency and reliability, only countries with complete age- and sex-stratified mortality data in 5-year intervals up to age 85 and above were included. Mortality trends were analyzed using locally weighted regression (LOESS) for crude and age-standardized rates, and joinpoint regression was employed to determine the average annual percent change (AAPC) from 2010 to 2023. Subgroup analyses by geographic region and income levels further refined insights into mortality disparities.
Key Findings
Data from 73 countries totaling 1,550,883 individuals (57.8% female) qualified for LOESS analysis, and 75 countries with 915,518 individuals (56.9% female) were included in joinpoint analysis. Globally, the age-standardized mortality rate from PE per 100,000 population was estimated to have declined from 3.49 (95% confidence interval [CI], 3.20–3.79) in 2001 to 2.42 (95% CI, 2.04–2.80) in 2023.
Regionally, notable reductions occurred in European regions, particularly Western Europe, where the standardized mortality rate fell sharply from 5.24 (95% CI, 4.75–5.74) to 2.25 (95% CI, 1.62–2.87). Contrastingly, African regions showed persistently high mortality rates with a minor decline from 4.23 (95% CI, 3.82–4.64) in 2001 to 3.90 (95% CI, 2.81–5.00) in 2023.
By economic classification, high-income countries experienced sustained declines in PE-related deaths, with rates dropping from 3.68 (95% CI, 3.28–4.08) to 2.20 (95% CI, 1.68–2.71). Conversely, lower- and middle-income countries exhibited an alarming rise in mortality, climbing from 0.92 (95% CI, 0.04–1.81) in 2001 to 4.82 (95% CI, 3.12–6.52) in 2023. This trend was especially pronounced in lower-middle-income countries, which had the largest increases in age-standardized mortality rates.
Expert Commentary
The divergent trends in PE mortality reflect underlying disparities in healthcare infrastructure, diagnostic capacities, access to anticoagulation therapies, and public health policies. The decline observed in affluent regions likely correlates with improved early detection, widespread use of direct oral anticoagulants, and enhanced critical care. Conversely, persistently elevated or rising mortality in lower-resourced settings may be attributable to delayed diagnosis, underreporting, and limited therapeutic options.
Potential study limitations include possible misclassification of cause of death and underreporting, particularly in countries with less robust vital statistics systems. These factors could underestimate true mortality. Nonetheless, the large multinational dataset and rigorous stratification lend credibility to the findings. Addressing these disparities demands a multi-layered approach encompassing clinician education, public awareness campaigns, expanded diagnostic resources, and policy reforms tailored to socioeconomic realities.
Conclusion
Over the past two decades, global pulmonary embolism-related mortality has decreased overall but remains disproportionately high in certain geographic and economic regions. The increase in PE mortality rates in lower-middle-income countries signals an urgent need for targeted interventions to improve PE diagnosis and management. Enhanced global collaboration, health system strengthening, and equitable access to modern therapies are essential to reduce preventable deaths. This study underscores the importance of ongoing surveillance and tailored public health strategies to mitigate PE burden worldwide.
References
Hagiya H, Harada K, Nishimura Y, Yamamoto M, Nishimura S, Yamamoto M, Niimura T, Osaki Y, Vu QT, Fujii M, Sako N, Takeda T, Hamano H, Zamami Y, Koyama T. Global trends in mortality related to pulmonary embolism: an epidemiological analysis of data from the World Health Organization mortality database from 2001 to 2023. EClinicalMedicine. 2025 Jul 31;86:103389. doi: 10.1016/j.eclinm.2025.103389. PMID: 40791890; PMCID: PMC12336653.
