Cancer-Associated Arterial Thromboembolism: The Overlooked Cardiovascular Threat in Oncology

For decades, cancer-associated thrombosis has been synonymous with venous thromboembolism (VTE), prompting major advances in risk assessment and thromboprophylaxis.

In contrast, arterial thromboembolism (ATE) – including acute myocardial infarction and ischemic stroke – has remained a comparatively neglected complication despite its profound impact on patient outcomes.

At the ISTH 2026 Congress, investigators from the Cosmos Hematology Research Collaborative, led by researchers from Baylor College of Medicine and collaborating institutions, presented one of the largest real-world analyses to date examining the burden of arterial thromboembolism in patients with cancer.

Drawing on data from more than 1.7 million patients across the United States, the study provides compelling evidence that arterial events are common, vary substantially across cancer types, and are strongly associated with mortality.

A Hidden Burden Beyond Venous Thrombosis

Thromboembolism is the second leading cause of death in patients with cancer, surpassed only by cancer progression.

While most clinical attention has focused on preventing venous thromboembolism, arterial events have received considerably less emphasis in both research and routine oncology practice.

Previous studies of cancer-associated ATE were largely limited to Medicare databases or single-center cohorts, restricting their generalizability. The current analysis leverages the Epic Cosmos electronic health record platform, providing a contemporary nationwide perspective on arterial thrombotic complications across diverse cancer populations.

The findings suggest that arterial thrombosis should no longer be viewed as an uncommon complication but rather as an integral component of cancer-associated cardiovascular disease.

A Nationwide Analysis of More Than 1.7 Million Patients

Investigators analyzed de-identified data from the Epic Cosmos database, which contains health records from more than 300 million patients across the United States. After applying eligibility criteria, the study included 1.7 million adults with newly diagnosed cancer from 190 healthcare institutions, making it one of the largest studies ever conducted on this topic.

Approximately 605,000 patients received systemic anticancer therapy within 90 days of diagnosis. The investigators evaluated the cumulative incidence of arterial thromboembolism, identified clinical predictors, and examined the relationship between arterial events and overall survival.

Importantly, arterial thromboembolism was defined specifically as acute myocardial infarction and ischemic stroke, allowing the study to focus on the most clinically significant arterial complications.

Arterial Events Are More Common Than Many Clinicians Appreciate

One of the most striking findings was the overall frequency of arterial thromboembolism. The cumulative incidence approached 5% within five years after cancer diagnosis, demonstrating that arterial events represent a substantial clinical burden.

Interestingly, patients receiving systemic therapy and those who remained untreated showed relatively similar overall incidence curves. This observation suggests that the increased arterial risk cannot be explained solely by anticancer treatment.

Instead, the biological effects of malignancy itself – including systemic inflammation, endothelial dysfunction, and hypercoagulability – appear to play a major role.

These findings reinforce the concept that cancer is not only a venous thrombotic disease but also an arterial vascular disease.

Not All Cancers Carry the Same Risk

The study revealed considerable variation in arterial thrombotic risk according to cancer type.

Patients with acute myeloid leukemia (AML), lung cancer, pancreatic cancer, biliary and gallbladder cancers, chronic myeloid disorders (including CMML, MDS, and MPN), upper gastrointestinal cancers, and multiple myeloma experienced the highest rates of arterial events during the first year after diagnosis.

In contrast, patients with breast, testicular, uterine, and cervical cancers demonstrated substantially lower risks.

Importantly, these differences persisted even after adjustment for age, cardiovascular disease, and other clinical variables, suggesting that tumor biology itself contributes significantly to arterial thrombosis.

The findings highlight the heterogeneity of thrombotic risk across malignancies and underscore the need for cancer-specific cardiovascular assessment.

Multiple Factors Drive Arterial Thrombosis

The analysis identified several independent predictors of arterial thromboembolism.

Older age, metastatic disease, cardiovascular comorbidities, and exposure to selected systemic anticancer therapies all contributed to increased risk.

Together, these findings support the understanding that arterial thrombosis results from a complex interaction between patient-related factors, underlying cardiovascular disease, cancer biology, inflammation, and treatment-induced vascular injury.

Rather than a single causative pathway, arterial thrombosis appears to emerge from multiple overlapping mechanisms, emphasizing the importance of individualized risk assessment.

A Powerful Marker of Poor Prognosis

Perhaps the most clinically important observation was the strong relationship between arterial thromboembolism and survival.

After adjustment for demographic characteristics, cancer stage, laboratory values, comorbidities, and treatment, myocardial infarction was associated with a 3.39-fold increase in mortality, while ischemic stroke was associated with a 2.85-fold increase in the risk of death.

Although the study cannot establish causality, these findings clearly demonstrate that arterial thrombotic events identify patients with markedly worse prognoses.

Beyond their immediate cardiovascular consequences, myocardial infarction and stroke may reflect more aggressive disease biology or greater systemic illness.

Strengths and Limitations

The study’s greatest strength lies in its exceptional scale. With data from 190 institutions and more than 1.7 million patients, it provides one of the most comprehensive assessments of cancer-associated arterial thromboembolism available to date.

The nationwide representation and longitudinal electronic health record data enhance the relevance of the findings to contemporary oncology practice.

Like all observational studies, however, important limitations remain.

The reliance on ICD coding introduces the possibility of outcome misclassification, mortality data are incomplete because the database is not linked to national death registries, and important variables such as smoking status, surgical procedures, and thoracic radiation exposure were unavailable.

In addition, peripheral arterial disease and acute limb ischemia were excluded from the study definition of arterial thromboembolism, suggesting that the true burden of arterial complications may be even greater than reported.

Implications for Cardio-Oncology

As advances in cancer therapy continue to improve survival, cardiovascular complications are becoming an increasingly important determinant of long-term outcomes.

This study suggests that patients with malignancies carrying particularly high arterial risk—including hematologic malignancies, lung cancer, pancreatic cancer, and upper gastrointestinal cancers—may benefit from closer cardiovascular surveillance and more individualized preventive strategies.

Unlike venous thromboembolism, however, validated risk prediction models and evidence-based prophylactic approaches for arterial thromboembolism remain largely absent. Developing these tools should become a priority for future cardio-oncology research.

Looking Beyond Venous Thrombosis

The findings presented at ISTH 2026 challenge clinicians to broaden their perspective on cancer-associated thrombosis. While prevention of venous thromboembolism remains essential, arterial events such as myocardial infarction and ischemic stroke also represent a significant and potentially preventable source of morbidity and mortality.

As oncology care becomes increasingly personalized, integrating cardiovascular risk assessment into routine cancer management may be critical for improving long-term patient outcomes. Future prospective studies will be needed to identify patients at greatest risk and determine whether targeted preventive strategies can reduce the burden of cancer-associated arterial thromboembolism.

Reference

Title: Cancer-associated arterial thromboembolism: real-world burden from a nationwide electronic health record database

Authors: Hyun Yong Koh, Senthil Sukumar, Zihan Yang, Preeti Preeti, Jun Y Jiang, Rock Bum Kim, Mrinal Ranjan, Danielle Guffey, Omid Jafari , Ang Li

Read the Full Article on JNCI

Written by Heghine Khachatryan, MD, PhD, Editor-in-Chief at Hemostasis Today, Head of Hemophilia and Thrombosis Center at Yeolyan Hematology and Oncology Center, Ministry of Health, Republic of Armenia.