Temporal trends in cancer-associated venous thromboembolism mortality: A nationwide analysis (1999–2020)

Abstract Background: Venous thromboembolism (VTE), including the dreadful pulmonary embolism (PE), is a well-known complication of cancer. It is also the leading cause of mortality in individuals with malignancy. Evidence-based prophylactic guidelines are available to counter thromboembolism and are increasingly being used in clinical practice. However, the effectiveness of these guidelines in reducing the VTE mortality at a population level is uncertain. Moreover, there is a scarcity of encompassing data assessing the national trends in VTE-related deaths among cancer patients. Specifically, it remains unclear whether mortality rates have declined, stabilized, or continued to rise in the current setting of modern oncologic advancements and supportive care. This study aims to demonstrate the temporal trends in mortality where the underlying cause of death was thromboembolism, and malignancy was a contributing cause. Methods: Data was extracted from the CDC Wide-Ranging Online Data for Epidemiologic Research (WONDER) multiple cause of death database from 1999 to 2020. The underlying cause of death was specified as pulmonary embolism (I26) or venous embolism including deep vein thrombosis (I82). Along with this, cancer ( C00 through C97) was selected as contributing cause. Individuals aged 15-84 were included. Age-adjusted mortality rates were analyzed using Joinpoint regression version 5.4.0.0. Model selection utilized 4,499 permutations with an alpha of 0.05. The confidence interval was calculated by a parametric method under a heteroscedastic error structure. Results: There were 168,965 deaths recorded where embolism was the primary cause, contributed by malignancy. In 2016, joinpoint regression identified a notable turning point. Between 1999 and 2016, the annual mortality rate changed by 0.67 percent each year, with a 95 percent confidence interval ranging from 0.42 to 0.91 percent, and a p value of less than 0.001. Following 2016, the mortality rate increased at a faster annual pace of 5.33 percent, with a 95 percent confidence interval ranging from 3.64 to 7.05 percent, and a p value of less than 0.001. This change signifies an almost eightfold escalation in the growth rate. The most significant numbers of deaths were recorded in California, Texas and Newyork. Male patients had a heavier impact compared to female patients. Black or African American individuals had the highest age-adjusted mortality rate (4.49), followed by White (2.86), American Indian or Alaska Native (1.74), and Asian or Pacific Islander (1.30). Conclusion: This study highlights a sharp and concerning rise in cancer-associated embolism deaths, especially after 2016. These findings challenge the belief that embolism in cancer patients is under control and point to a serious gap in care. Urgent efforts are needed to enhance prevention strategies, raise clinical awareness, and improve healthcare delivery. Without targeted intervention, this escalating trend may continue, exacerbating existing healthcare disparities. Moreover, the disproportionate burden observed among Black or African American individuals signifies the need to address racial disparities in thromboembolism prevention and cancer care.