Cardiotoxic effects of angiogenesis inhibitors

The development of new therapies for cancer has led to dramatic improvements in survivorship. Angiogenesis inhibitors represent one such advancement, revolutionising treatment for a wide range of malignancies. However, these drugs are associated with cardiovascular toxicities which can impact optimal cancer treatment in the short-term and may lead to increased morbidity and mortality in the longer term. Vascular endothelial growth factor inhibitors (VEGFIs) are associated with hypertension, left ventricular systolic dysfunction (LVSD) and heart failure as well as arterial and venous thromboembolism, QTc interval prolongation and arrhythmia. The mechanisms behind the development of VEGFI-associated LVSD and heart failure likely involve the combination of a number of myocardial insults. These include direct myocardial effects, as well as secondary toxicity via coronary or peripheral vascular damage. Cardiac toxicity may result from the ‘on-target’ effects of VEGF inhibition or ‘off-target’ effects resulting from inhibition of other tyrosine kinases. Similar mechanisms may be involved in the development of VEGFI-associated right ventricular (RV) dysfunction. Some VEGFIs can be associated with QTc interval prolongation and an increased risk of ventricular and atrial arrhythmia. Further pre-clinical and clinical studies and trials are needed to better understand the impact of VEGFI on the cardiovascular system. Once mechanisms are elucidated, therapies can be investigated in clinical trials and surveillance strategies for identifying VEGFI-associated cardiovascular complications can be developed.