Chemotherapeutic Agents and the Risk of Ischemia and Arterial Thrombosis

Saamir A. Hassan, Nicolas Palaskas, Peter Kim, Cezar Iliescu, Juan Lopez-Mattei, Elie Mouhayar, Rohit Mougdil, Kara Thompson, Jose Banchs, Syed Wamique Yusuf

Numerous chemotherapeutic agents have been associated with the development of ischemia and arterial thrombosis. As newer therapies have been developed to treat cancer, some of these chemotherapy drugs have been implicated in the development of vascular disease. In this review, we will summarize the most common chemotherapeutic drug classes that may play a role in the development of ischemic heart disease. Angiogenesis inhibitors, alkylating agents, antimetabolites, antimicrotubules, and proteasome inhibitors have a number of cardiovascular toxicities. The possible mechanisms of action of these drugs leading to ischemic complications are varied but include endothelial dysfunction, platelet aggregation, reduced levels of nitrous oxide (NO), and elevated levels of reactive oxygen species (ROS), and vasospasm. While some drugs act through multiple pathways that result in the development of ischemic heart disease, others such as the antimetabolites and antimicrotubules appear to primarily cause vasospasm. Furthermore, while aromatase inhibitors increase the risk of heart disease in comparison to tamoxifen in large studies, this finding likely occurs because of a protective role of tamoxifen on cardiovascular risk factors rather than a direct effect of aromatase inhibitors. Angiogenesis inhibitors, alkylating agents, antimetabolites, antimicrotubules, and proteasome inhibitors can lead to ischemic complications in patients with cancer. Many of these drugs have proven to be effective in improving cancer prognosis, but their possible cardiovascular effects have to be carefully monitored and treated. Treatment of ischemic complications in the setting of cancer therapy should focus on the optimal medical management of known cardiovascular risk factors and follow an evidence-based approach.