Thrombotic and bleeding risk of angiogenesis inhibitors in patients with and without malignancy

Over the past two decades, therapies targeting angiogenesis have developed into a major class of cancer therapeutics. The vascular endothelial growth factor (VEGF) family of signaling proteins, a group of potent angiogenic growth factors, and their receptors represent the main targets of this therapeutic class. To date, 16 antiangiogenic agents have been approved in the United States for the treatment of cancer and several more are in development. An important consideration with antiangiogenic therapy is toxicity, in particular thrombotic and bleeding risks. These complications have emerged as a major clinical concern that may affect the use of these agents in patients both with and without cancer who may already have an elevated risk of thrombosis and bleeding. Although these agents are frequently considered together as a class when contemplating their bleeding and thrombotic risks, in fact the risks for venous thromboembolism, arterial thrombosis, and bleeding vary significantly between different classes of antiangiogenic agents and even among different agents within a class. In this narrative review, we describe the literature investigating the venous and arterial thrombotic and bleeding risks associated with the currently available antiangiogenic drugs. In addition, we discuss these specific complications in the context of both cancer therapy as well as the management of nonmalignant disorders now managed with antiangiogenic agents, including hereditary hemorrhagic telangiectasia and neovascular age‐related macular degeneration.