Renal response to a dual vasopressin antagonist in acute heart failure: a post-hoc analysis from the AVANTI trial
L Cosic, D C H Ceelen, G H D Voordes, J M Ter Maaten, R T Gansevoort, K Damman, S R Goldsmith, D Burkhoff, F Gustafsson, K Duarte, L Monzo, N Girerd, F Zannad, J E Udelson, A A VoorsAbstract
Background
In a randomized placebo-controlled trial of hospitalized heart failure (HF) patients, the dual vasopressin 1a/2 receptor antagonist pecavaptan did not increase weight loss at 30 days. However, little is known about the renal effects of vasopressin antagonists. In this analysis, we investigated the effects of pecavaptan related to kidney function.
Methods
The AVANTI trial randomized hospitalized HF patients with residual congestion to a daily oral dose of 30 mg pecavaptan or placebo adjunctive to regular care. Changes in kidney function over time and treatment response according to baseline estimated glomerular filtration rate (eGFR) were assessed.
Results
Among 438 patients (median baseline eGFR 53 [IQR 42–68] mL/min/1.73m²), pecavaptan was associated with a smaller increase in eGFR (difference in change between pevacaptan and placebo -2.97 mL/min/1.73m2; treatment x time p-interaction 0.003) and an increased urinary albumin-creatinine ratio (UACR, geometric mean ratio 1.75; p-interaction 0.002) between day 7 and day 30 compared to placebo. In contrast, pecavaptan treatment significantly reduced blood urea nitrogen (BUN, difference -0.69 mg/dL; p-interaction 0.041). Baseline kidney function did not modify the effect of pecavaptan on weight loss at day 7 and day 30 (p-interaction 0.694 and 0.609), but the effects of pecavaptan on increase in serum sodium and osmolality from baseline to day 30 were more pronounced in patients with eGFR > 60 mL/min/1.73m² (p-interaction 0.020 and 0.036).
Conclusion
In hospitalized HF patients, pecavaptan relatively decreased eGFR and increased UACR, which might be related to volume changes. Pecavaptan reduced BUN most likely through the inhibition of vasopressin driven urea reabsorption in the inner medullary collecting duct. Finally, baseline kidney function did not modify the effect of pecavaptan on weight loss.Linear mixed effects modelling of eGFRFor image description, please refer to the figure legend and surrounding text.Linear mixed effects UACR and BUNFor image description, please refer to the figure legend and surrounding text.