Associations Between Antihypertensive Drugs and Patterns of Blood Pressure Changes: a Strategy to Reduce the Burden of Anti-VEGF Induced Hypertension

Background: High blood pressure is a common complication observed in cancer patients prescribed a class of medications known as anti-VEGF drugs. Increased blood pressure, also known as hypertension, increases the risk of heart attacks and strokes, thus adversely affecting survival and quality of life in this patient group. However, little is known about the mechanisms leading to high blood pressure with anti-VEGF drugs. As a result, the management of anti-VEGF drug-induced hypertension is largely empirical, hence sub-optimal. A better knowledge of effects of specific blood pressure lowering drugs, i.e. antihypertensives, on anti-VEGF drug-induced hypertension would optimize therapeutic management and reduce the risk associated with hypertension and proteinuria in patients with cancer.

Methods: The investigators will access the datasets of two GSK clinical trials using the anti-VEGF drug pazopanib, i.e. VEG108844 and VEG105192, in order to 1) determine the way blood pressure changes over time after commencing anti-VEGF treatment; 2) identify whether there are any relationships between pre-study and baseline blood pressure values, treatment with specific antihypertensive drugs, and changes in blood pressure after commencing anti-VEGF treatment; and 3) identify whether specific antihypertensive drugs and drug combinations, prescribed either before or after commencing anti-VEGF treatment, lead to a better blood pressure control and prevent proteinuria during anti-VEGF treatment. Specific statistical analyses will be conducted to assess and identify associations and will account for other patient's characteristics and repeated observations over time. The investigators plan to conduct this study over 6 months.

Studies VEG108844 and VEG105192 have been selected as they investigate the same anti-VEGF drug, pazopanib, in a homogeneous group, i.e. patients with renal cancer. At the same time, inclusion of a placebo arm as well as a treatment arm with a different anti-VEGF drug, sunitimib, will allow initial comparisons across different groups.

The results deriving from this study will provide important knowledge on 1) patterns of blood pressure changes with anti-VEGF drugs and 2) whether specific antihypertensive drugs or drug classes might be better than others in preventing and managing anti-VEGF induced hypertension and proteinuria. This research will pave the way for further clinical studies aimed at testing the hypotheses generated. The evidence generated could contribute to the development of national and international guidelines for the management of anti-VEGF induced hypertension.

The investigators plan to disseminate the findings at national and international oncology and/or hypertension conferences and by publishing the results in peer-reviewed scientific journals.