ABSTRACT
PURPOSE OF REVIEW: The purpose of this paper is to identify commonly used tyrosine kinase inhibitors (TKIs) that are associated with hypertension, primarily, vascular endothelial growth factor (VEGF) signaling pathway (VSP) inhibitors. We review the incidence, mechanism, and strategies for management of TKI-induced HTN. We hope to provide clinicians with guidance on how to manage similar clinical scenarios. RECENT FINDINGS: Many of the newer VSP inhibitors are reviewed here, including cediranib, axitinib, pazopanib, and ponatinib. Trials utilizing prophylactic treatment with angiotensin system inhibitors (ASIs) are discussed as well as recent data showing an improvement in overall survival and progression-free survival in patients on ASIs and TKI-induced hypertension. The incidence of TKI-induced HTN among the VEGF inhibitors ranges from 5 to 80% and is dose dependent. Newer generation small-molecule TKIs has a lower incidence. The mechanism of action involves VSP inhibition, leading to decreased nitric oxide and increased endothelin production, which causes vasoconstriction, capillary rarefaction, and hypertension. ASIs and calcium channel blockers are first-line therapy for treatment and are associated with improved overall survival. Nitrates and beta-blockers are associated with in vitro cancer regression; however, there is a paucity of trials regarding their use as an anti-hypertensive agent in the TKI-induced HTN patient population.
Subject(s)
Hypertension/chemically induced , Hypertension/drug therapy , Protein Kinase Inhibitors/adverse effects , Protein-Tyrosine Kinases/antagonists & inhibitors , Angiotensins/antagonists & inhibitors , Antihypertensive Agents/therapeutic use , Calcium Channel Blockers/therapeutic use , Humans , Hypertension/physiopathology , Neoplasms/drug therapy , Protein Kinase Inhibitors/therapeutic use , Signal Transduction/drug effects , Vascular Endothelial Growth Factors/antagonists & inhibitors , Vascular Endothelial Growth Factors/metabolismABSTRACT
BACKGROUND: Hodgkin's lymphoma (HL) comprises of 4% of malignancies diagnosed in children from birth to 14 years of age. While overall survival rates have increased, HL survivors can be at risk of late cardiovascular complications from radiotherapy. HL survivors with a history of mediastinal RT have been found to have an increased incidence of myocardial infarction, angina, congestive heart failure, and valvular disorders compared to the general population. METHODS: A 33 year old female with a history of HL status post chemotherapy and mediastinal radiation 11 years ago became symptomatic with multivessel coronary artery disease with aggressive progression of her disease despite coronary bypass graft surgery, patch angioplasty of the left main coronary artery (LMCA) with an extracellular bioscaffold, and repeated percutaneous coronary intervention of the LMCA. She eventually underwent orthotopic heart transplant and did well postoperatively. RESULTS: Histopathological analysis of the explanted heart revealed a variety of sequelae of radiation arteritis, including thrombosis of both native vessels and arterial grafts, intimal hyperplasia and involvement of the bioscaffold in the left main coronary vasculature. The bioscaffold did not contribute significantly to the stenosis within the LMCA. CONCLUSION: Our case demonstrates an unusual indication for OHT due to severe refractory radiation induced CAD, as well the wide spectrum of the histopathologic manifestations of radiation induced arteritis.
