Abstract P406: Aprocitentan, A Novel Endothelin Receptor Antanognist, In Older Patients With Difficult-to-control Hypertension

Abstract

Background: In older adults, hypertension (HTN) control can be difficult despite multiple therapies, especially in those with altered kidney function. The PRECISION study showed that aprocitentan (APRO), a dual endothelin receptor antagonist12.5 or 25 mg daily decreases blood pressure (BP) in patients (Pts) with resistant HTN. We evaluated APRO BP lowering in Pts aged ≥ 65 years. Methods: Pts had sitting unattended automated office systolic BP (SBP) ≥ 140 mmHg after switching their antihypertensives (anti-HTN) (except beta-blockers) to a standardized therapy (ST) of amlodipine, valsartan and HCTZ. Reductions in office and ambulatory BP; and safety were assessed in 3 sequential parts over a 48-week period as follows: 4-week double-blind (DB) APRO 12.5 mg, APRO 25 mg, PBO; 32-week single-blind APRO 25 mg; and 12-week DB withdrawal APRO 25 mg, PBO. Results: In PRECISION, 321 Pts were aged ≥ 65 years. Of those, 202 (63%) were obese, 115 (36%) had chronic kidney disease stage 3-4, and 209 (65%) were on ≥ 4 anti-HTN prior switching to ST.At Week 4, APRO reduced office SBP, PBO adjusted SBP is: APRO 12.5 mg -5.64 and APRO 25 mg -4.63 mmHg in Pts 65–< 75 years; and APRO 12.5 mg -6.75 and APRO 25 mg -12.85 mmHg in Pts ≥ 75 years. APRO 25 mg maintained BP reduction over 32 weeks but this disappeared at Week 40 in those randomized to PBO at Week 36, PBO adjusted SBP is +5.70 mmHg in Pts 65–< 75 years; +3.51 mmHg in Pts ≥ 75 years. Ambulatory BP confirmed office BP reductions with both APRO doses, particularly with APRO 25 mg on nighttime SBP at Week 4 in Pts ≥ 75 years: 12.5 mg: -8.8; 25 mg: -14.8; PBO +1.0 mmHg. At Week 4, the most frequent adverse event (AE) was peripheral edema: 7.7%, 12.9%, and 2.3% in Pts 65–< 75 years, and 18.2%, 22.7%, and 3.6% in Pts ≥ 75 years, with APRO 12.5 mg, APRO 25 mg, and PBO, respectively. Edema was managed with additional diuretics. 4 Pts discontinued due to edema; none had received additional diuretics. 7 Pts (APRO 25 mg) were hospitalized for heart failure; 4 of them had switched from loop or more than one diuretic to HCTZ.No orthostatic hypotension events occurred. Conclusion: In older resistant HTN Pts, APRO added to ≥ 3 anti-HTN substantially decreased office and ambulatory BP. The most frequent AE was peripheral edema, which rarely led to treatment discontinuation.