Randomized Trial of Etelcalcetide for Cardiac Hypertrophy in Hemodialysis

Abstract

Rationale: Left ventricular hypertrophy (LVH) is highly prevalent in patients with chronic kidney disease and increases their risk of cardiac events and mortality. FGF23 (fibroblast growth factor 23) and parathyroid hormone levels, which are associated with the development of LVH, rise progressively with declining renal function. Objectives: To determine whether FGF23 suppression by calcimimetic therapy may reduce LVH progression in comparison to FGF23 elevation under vitamin D analogs at equal parathyroid hormone suppression under either therapy as well as tight volume control. Methods and Results: We conducted a single-blinded trial with 1:1 block randomization to investigate the effect of the intravenous treatment with etelcalcetide versus alfacalcidol on LVH progression in 62 maintenance hemodialysis patients with secondary hyperparathyroidism and LVH. In the intention-to-treat analysis of 59 patients, the mean difference in the change of left ventricular mass index determined by cardiac magnetic resonance imaging from baseline to 12 months of treatment was −6.9 g/m 2 (95% CI, −12.6 to −1.2, P =0.022) in the etelcalcetide compared with the alfacalcidol group. The effect estimate was −8.2 g/m 2 (95% CI, −14 to −2.4) in the per-protocol analysis on 52 patients. The trajectories of parathyroid hormone, phosphate, and αKlotho were similar in both groups throughout follow-up. FGF23 levels, which showed a strong positive association with left ventricular mass index, were decreasing under etelcalcetide and increasing under alfacalcidol at similar parathyroid hormone suppression. Mild hypocalcemia was the most common adverse event under etelcalcetide. Blood pressure and the distribution of antihypertensive medications were similar between groups. Conclusions: In this trial, we were able to show that FGF23 suppression by etelcalcetide inhibited the progression of LVH compared with alfacalcidol in hemodialysis patients. A successful prevention of increasing hypertrophy may reduce the risk of sudden cardiac death in this population. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT03182699.