Renin-Angiotensin-Aldosterone System Modulates Blood Pressure Response During Vascular Endothelial Growth Factor Receptor Inhibition

Objectives: This study postulated that antihypertensive therapy with renin-angiotensin-aldosterone system (RAAS) inhibition may mitigate vascular endothelial growth factor inhibitor (VEGFi)–mediated increases in blood pressure more effectively than other antihypertensive medications in patients receiving VEGFi therapy. Background: VEGFi therapy is commonly used in the treatment of cancer. One common side effect of VEGFi therapy is elevated blood pressure. Evidence suggests that the RAAS may be involved in VEGFi-mediated increases in blood pressure. Methods: This retrospective cohort analysis was performed using a de-identified version of the electronic health record at Vanderbilt University Medical Center in Nashville, Tennessee. Subjects with cancer who were exposed to VEGFi therapy were identified, and blood pressure and medication data were extracted. Changes in mean systolic and diastolic blood pressure in response to VEGFi therapy in patients receiving RAAS inhibitor (RAASi) therapy before VEGFi initiation were compared with changes in mean systolic and diastolic blood pressure in patients not receiving RAASi therapy before VEGFi initiation. Results: Mean systolic and diastolic blood pressure rose in both groups after VEGFi use; however, patients who had RAASi therapy before VEGFi initiation had a significantly lower increase in systolic blood pressure as compared with patients with no RAASi therapy (2.46 mm Hg [95% confidence interval: 0.7 to 4.2] compared with 4.56 mm Hg [95% confidence interval: 3.5 to 5.6], respectively; p = 0.034). Conclusions: In a real-world clinical population, RAASi therapy before VEGFi initiation may ameliorate VEGFi-mediated increases in blood pressure. Randomized clinical trials are needed to further our understanding of the role of RAASi therapy in VEGFi-mediated increases in blood pressure.