Dietary sodium restriction prevents vascular endothelial growth factor inhibitor-induced hypertension

Abstract

BACKGROUND: Vascular endothelial growth factor inhibitors (VEGFIs) are effective anticancer agents which often induce hypertension. VEGFI-induced hypertension is sodium-sensitive in animal studies. Therefore, the efficacy of dietary sodium restriction (DSR) to prevent VEGFI-induced hypertension in cancer patients was studied. METHODS: Cancer patients with VEGFI-induced hypertension (day mean >135/85 mmHg or a rise in systolic and/or diastolic BP ≥ 20 mmHg) were treated with DSR (aiming at <4 g salt/day). The primary endpoint was the difference in daytime mean arterial blood pressure (MAP) increase between the treatment cycle with and without DSR. RESULTS: During the first VEGFI treatment cycle without DSR, mean daytime MAP increased from 95 to 110 mmHg. During the subsequent treatment cycle with DSR, mean daytime MAP increased from 94 to 102 mmHg. Therefore, DSR attenuated the increase in mean daytime MAP by 7 mmHg (95% CI 1.3-12.0, P = 0.009). DSR prevented the rise in the endothelin-1/renin ratio that normally accompanies VEGFI-induced hypertension (P = 0.020) and prevented the onset of proteinuria: 0.15 (0.10-0.25) g/24 h with DSR versus 0.19 (0.11-0.32) g/24 h without DSR; P = 0.005. DISCUSSION: DSR significantly attenuated VEGFI induced BP rise and proteinuria and thus is an effective non-pharmacological intervention.

2023 ESH Guidelines for the management of arterial hypertension The Task Force for the management of arterial hypertension of the European Society of Hypertension

“…in response to VEGF inhibitor treatment. Nevertheless, sodium restriction may be helpful as a maximum intake of 4 g sodium per day in combination with dietary counseling has recently been shown to attenuate the VEGF inhibitor-induced BP rise by almost 50% in a small (pilot) study (16 patients) [1597]. In a retrospective cohort study involving 343 cancer patients that were treated with oral VEGF inhibitors (sorafenib, sunitinib, pazopanib, regorafenib, lenvatinib or cabozantinib), about half of the included patients exhibited significant BP increases (20 mmHg in SBP or 10 mmHg in DBP).…”