Frequency, risk factors, and impact on mortality of arterial thromboembolism in patients with cancer

Abstract

In contrast to venous thromboembolism, little is known about arterial thromboembolism in patients with cancer. The aim of this study was to quantify the risk and explore clinical risk factors of arterial thromboembolism in patients with cancer, and investigate its potential impact on mortality. Patients with newly-diagnosed cancer or progression of disease after remission were included in a prospective observational cohort study and followed for two years. Between October 2003 and October 2013, 1880 patients (54.3% male; median age 61 years) were included. During a median follow up of 723 days, 48 (2.6%) patients developed arterial thromboembolism [20 (41.7%) myocardial infarction, 16 (33.3%) stroke and 12 (25.0%) peripheral arterial events], 157 (8.4%) developed venous thromboembolism, and 754 (40.1%) patients died. The cumulative 3-, 6-, 12-, and 24-month risks of arterial thromboembolism were 0.9%, 1.1%, 1.7%, and 2.6%, respectively. Male sex (subdistribution hazard ratio=2.9, 95%CI: 1.5-5.6; P=0.002), age (subdistribution hazard ratio per 10 year increase=1.5, 1.2-1.7; P<0.001), hypertension (3.1, 1.7-5.5; P<0.001), smoking (2.0, 1.1-3.7; P=0.022), lung cancer (2.3, 1.2-4.2; P=0.009), and kidney cancer (3.8, 1.4-10.5; P=0.012) were associated with a higher arterial thromboembolism risk. Furthermore, the occurrence of arterial thromboembolism was associated with a 3.2-fold increased risk of all-cause mortality (hazard ratio=3.2, 95%CI: 2.2-4.8; P<0.001). Arterial thromboembolism is a less common complication in patients with cancer than venous thromboembolism. The risk of arterial thromboembolism is high in patients with lung and kidney cancer. Patients with cancer who develop arterial thromboembolism are at a 3-fold increased risk of mortality.

Figure 1.

Cumulative incidence of arterial thromboembolism (ATE) in patients with cancer. For estimation we used a competing risk cumulative incidence estimator. Venous thromboembolism (VTE) and death-from-any-cause were considered as competing risk events. The dashed line represents 95% confidence bands.

Figure 2.

Time-dependent rates of arterial thromboembolism (ATE) and venous thromboembolism (VTE) over two years of follow up. While the rate of VTE was highest during the first six months of follow up and then declined, the risk of ATE did not have a peak and remained relatively constant during follow up. The curves were predicted with a flexible parametric regression model on the log-cumulative-hazard scale (Stata routine stpm2).

Figure 3.

Cumulative incidence of arterial thromboembolism (ATE) according to cancer type. A competing risk cumulative incidence estimator was used. For clarity, only selected tumor entities are compared. A Gray’s test was used to test for differences between cancer types (P<0.001), venous thromboembolism and death-from-any-cause were considered as competing risk event.

Figure 4.

Cumulative impact of cardiovascular risk factors on the risk of arterial thromboembolism (ATE). Competing risk analysis was used to analyze the incidence of ATE, considering venous thromboembolism (VTE) and death-from-any-cause as competing risk events. SHR: subdistribution hazard ratio;CVRF: cardiovascular risk factors.

Figure 5.

Landmark analysis of predicted overall survival according to arterial thromboembolism (ATE) status after three months of follow up. 1745 patients survived for at least three months (“landmark time”), of whom 13 had developed ATE within the first three months and had survived until the landmark time. Four patients had developed ATE within the first three months and died before the landmark time; 31 patients had developed ATE after the landmark time. “Predicted” instead of “observed” overall survival was chosen due to the small numbers of patients who had developed ATE within the first three months (n=13).