Cardiovascular Toxicity of Angiogenesis Inhibitors Among Patients With Cancer in Taiwan: A Nested Case-Control Study

Abstract

Background: Research on the cardiovascular toxicity of angiogenesis inhibitors among patients with cancer in Taiwan is lacking. This observational study explored the risk of major adverse cardiovascular events (MACEs) associated with angiogenesis inhibitors in Taiwan.

Methods and results: We conducted a nested case-control study using the TCR (Taiwan Cancer Registry) linked with the Taiwan National Insurance Claim Database. We matched every case with 4 controls using risk-set sampling by index date, age, sex, cancer type, and cancer diagnosis date. Conditional logistic regression was used to evaluate the risks of MACEs and different cardiovascular events using propensity score adjustment or matching. Sensitivity analyses were used to evaluate the risks matched by cancer stages or exposure within 1 year. Among a cohort of 284 292 after the exclusion of prevalent cases, the incidences of MACEs among the overall cohort and those exposed to angiogenesis inhibitors were 22.5 and 32.5 events per 1000 person-years, respectively. We matched 17 817 cases with 70 740 controls, with a mean age of 74.9 years, and 56.8% of patients were men. After propensity score adjustment, angiogenesis inhibitors were associated with increased risks of MACEs (odds ratio, 4.56; 95% CI, 1.78-11.59). Significantly increased risks were noted for heart failure hospitalization, myocardial infarction, cerebrovascular accident, and venous thromboembolism, but not for new-onset atrial fibrillation. Similar results were observed after matching by cancer stage or restriction of 1-year exposure.

Conclusions: Angiogenesis inhibitors were associated with increased risks of MACEs among patients with various malignancies in Taiwan but were not associated with new-onset atrial fibrillation.

Keywords: angiogenesis inhibitors; cardiotoxicity; cardiovascular system; vascular endothelial growth factors.

Figure 1. The diagram of the cohort selection and matching process.

MACE indicates major adverse cardiovascular event.

Figure 2. Subgroup analysis of risk of MACEs after exposure to angiogenesis inhibitors.

MACEs indicates major adverse cardiovascular events; and OR, odds ratio.