Abstract MP07: Efficacy and safety of aprocitentan in patients with resistant hypertension and elevated NT-proBNP

Background and Objectives: The endothelin ETA/ETB receptor antagonist aprocitentan (APRO) decreased blood pressure (BP) in patients with confirmed resistant hypertension (RHT) in the PRECISION study. 19.6% of the overall population (143 subjects) had a reported history of Heart Failure (HF). It is well known that in subjects with RHT, HF is often underdiagnosed. In PRECISION, NT-proBNP (a marker of HF) was measured. Here we report the efficacy and safety of APRO in patients with increased NT-proBNP. Methods: 730 patients with RHT were switched to a standardized fixed-dose combination of amlodipine/valsartan/hydrochlorothiazide from their existing anti-hypertensive and diuretic medication and then randomized to APRO (12.5 mg or 25 mg) or placebo in PRECISION. This analysis considers subjects with baseline blood levels of NT-proBNP >125 pg/mL. Change in BP, incident cases of edema/fluid retention and change in body weight were assessed. Descriptive statistics are presented. Results: 236 enrolled subjects (32.3%) had NT-proBNP levels from 125–1125 pg/mL. At Week 4, APRO 12.5 mg decreased trough sitting systolic BP (SiSBP) by mean (SD) 14.2 (16.7) mm/Hg, APRO 25 mg by 15.8 (13.5) mm/Hg and placebo by 9.9 (18.0) mm/Hg, confirming that the effect was greater for APRO than placebo with no apparent difference between 12.5 and 25 mg, as observed in the overall population enrolled in PRECISION. The effect was maintained with APRO 25 mg at Week 36 with a decrease of 18.4 (15.2) mm/Hg versus baseline. Adverse events of edema/fluid retention were reported with an incidence of 13.4%, 25.7% and 1.2% in the 12.5 mg, 25 mg and placebo group, respectively, at Week 4. During the SB part up to 36 weeks edema/fluid retention was reported by 26.1% of subjects with 25 mg. Body weight change at Week 4 was +0.5, +0.7 and -0.2 Kg with 12.5 mg, 25mg and placebo, respectively. This weight increase was reversible: a subsequent decrease resulted in a difference versus baseline of 0.4 kg at Week 36. NT-proBNP ratio vs baseline (geometric mean) was 0.94, 0.86 and 0.78 with 12.5 mg, 25 mg and placebo, respectively, at Week 4. There was no increase over time, the ratio vs baseline was still below 1 (0.91) at Week 36. Conclusion: Aprocitentan is effective in patients with RHT and elevated NT-proBNP. Edema and fluid retention are more common in this sub-group compared with the overall population included in PRECISION, but it is not linked to significant weight gain or increase of NT-proBNP.