Arterial Thromboembolism in Cancer Patients: A Danish Population-Based Cohort Study

Abstract

Background: The relation between cancer and arterial thromboembolism (ATE) remains unclear.

Objectives: The purpose of this study was to evaluate ATE risk in cancer patients.

Methods: Danish registries were used to identify all cancer patients between 1997 and 2017, each matched to three cancer-free comparator individuals. ATE was defined as the composite of myocardial infarction, ischemic/unspecified stroke, and peripheral arterial occlusion. A competing risk approach was used to compute cumulative incidences and subdistribution hazard ratios (SHRs). Cause-specific hazard ratios (HRs) were calculated using Cox regression. Among cancer patients, mortality risk was estimated in Cox regression analysis by treating ATE as a time-varying exposure. Patients were followed for 12 months.

Results: The study included 458,462 cancer patients and 1,375,386 comparator individuals. In the 6-month period following cancer diagnosis/index date, the cumulative incidence for ATE was 1.50% (95% confidence interval [CI]: 1.47% to 1.54%) in cancer patients and 0.76% (95% CI: 0.75% to 0.77%) in comparator individuals (HR: 2.36; 95% CI: 2.28 to 2.44). Among cancer patients age <65 years, 65 to 75 years, and >75 years, this was 0.79% (95% CI: 0.74% to 0.83%), 1.61% (95% CI: 1.55% to 1.67%), and 2.30% (95% CI: 2.22% to 2.38%), respectively. Other predictors for ATE among cancer patients were prior ATE (SHR: 2.96; 95% CI: 2.77 to 3.17), distant metastasis (adjusted SHR: 1.21; 95% CI: 1.12 to 1.30), and chemotherapy (SHR: 1.47; 95% CI: 1.33 to 1.61). Among cancer patients, ATE was associated with an increased risk of mortality (HR: 3.28; 95% CI: 3.18 to 3.38).

Conclusions: Cancer patients are at increased risk of ATE. Clinicians should be aware of this risk, which is associated with mortality.

Keywords: CI, confidence interval; HR, hazard ratio; SHR, subdistribution hazard ratio; arterial occlusion; arterial thromboembolism; cancer; cohort study; ischemic stroke; myocardial infarction; neoplasm.

Graphical abstract

Figure 1

12-Month Cumulative Incidence Curves for ATE, Myocardial Infarction, and Ischemic Stroke Cumulative arterial thromboembolism (ATE) (A), myocardial infarction (B), and ischemic stroke (C) incidence for patients with cancer and for the matched comparator cohort in the 12 months after cancer diagnosis/index date. The cumulative incidence was calculated with a competing risk approach.

Figure 2

Incidence Rate of ATE for Each Cancer Type During the First 6 Months After Cancer Diagnosis for Patients <65, 65 to 75, and >75 Years The incidence rate was calculated as number of events per 1,000 person years. The gray bar depicts the 95% confidence interval. ATE = arterial thromboembolism.

Figure 3

Incidence Rate of Myocardial Infarction for Each Cancer Type During the First 6 Months After Cancer Diagnosis for Patients <65, 65 to 75, and >75 Years The incidence rate was calculated as number of events per 1,000 person years. The gray bar depicts the 95% confidence interval.

Figure 4

Incidence Rate of Stroke for Each Cancer Type During the First 6 Months After Cancer Diagnosis for Patients <65, 65 to 75, and >75 Years The incidence rate was calculated as number of events per 1,000 person years. The gray bar depicts the 95% confidence interval.

Central Illustration

Cancer Patients at Increased Risk of Arterial Thromboembolism The 12-month cumulative incidence of arterial thromboembolism (ATE) is higher for cancer patients than for comparator individuals. In cancer patients, ATE is associated with an increased risk of mortality. Age, prior arterial thromboembolism, distant metastasis, and chemotherapy were important predictors for ATE. ATE was defined as the composite of myocardial infarction, ischemic and unspecified stroke, and peripheral arterial occlusion. CI = confidence interval; HR = hazard ratio.