Abstract P068: Dietary Sodium Restriction Prevents Vascular Endothelial Growth Factor Inhibitor-Induced Hypertension

Abstract

Vascular endothelial growth factor tyrosine kinase inhibitors (VEGFIs) are effective anti-cancer agents which often induce hypertension. VEGFI-induced hypertension was demonstrated to be sodium-sensitive in preclinical studies, but the sodium sensitivity in humans and its potential as a preventive antihypertensive strategy in the clinical situation remains unknown. Therefore, the efficacy of dietary sodium restriction (DSR) to prevent VEGFI-induced hypertension was studied in patients with cancer. To this end, patients with cancer who developed VEGFI-induced hypertension (defined as daytime systolic blood pressure (SBP) > 135 mmHg and/or diastolic blood pressure (DBP) > 85 mmHg or a rise in SBP/DBP of ≥ 20 mmHg) were treated with DSR under supervision of a specialized dietician (aiming at < 4 g salt/day). The primary endpoint was the difference in daytime mean arterial blood pressure (MAP) increase between the VEGFI treatment cycle with and without concomitant DSR. Of the forty-nine screened patients, twenty (41%) patients were eligible for the DSR intervention based on their VEGFI-induced blood pressure rise, of whom sixteen successfully completed the intervention. During the first VEGFI treatment cycle without DSR, mean daytime MAP increased from 95 mmHg to 110 mmHg. During the subsequent treatment cycle with concomitant DSR, mean daytime MAP increased from 94 mmHg to 102 mmHg. Therefore, DSR attenuated the increase in mean daytime MAP by 7 mmHg (95% CI 1.3 to 12.0, P = 0.009). DSR prevented the rise in the endothelin-1/renin ratio that normally accompanies VEGFI-induced hypertension ( P = 0.020) and slightly prevented the onset of proteinuria: 0.15 (0.10-0.25) g/24h with DSR versus 0.19 (0.11-0.32) g/24h without DSR; P = 0.005. For two patients, proteinuria decreased from common terminology criteria of adverse events (CTCAE) grade and 3 during the treatment cycle without DSR to grade 1 and grade 2 during DSR, respectively. In conclusion, DSR significantly attenuated the VEGFI-induced BP rise, the increase in the endothelin-1/renin ratio and the onset of proteinuria. Therefore, DSR is an effective and attractive non-pharmacological intervention for patients with VEGFI-induced hypertension and its sequelae.