Abstract 118: Effects Of Aprocitentan, A Dual Endothelin Receptor Antagonist, On Blood Pressure In Black/African American Patients With Resistant Hypertension: Results From A Randomized, Controlled Study (PRECISION) Including A Withdrawal Phase

Abstract

Background: Resistant hypertension is prevalent among Black/African American drug-treated hypertensives and may increase cardiovascular risk. We evaluated aprocitentan (APRO) for BP lowering in Black patients with resistant hypertension. Methods: Patients had sitting unattended automated office systolic BP (SBP) ≥140 mmHg despite use of ≥3 antihypertensives of different classes in the year prior. After 4 weeks of combination therapy (amlodipine, valsartan, hydrochlorothiazide), those still hypertensive could enter a 4-week single-blind placebo (PBO) run-in period, followed by a 4-week double-blind period wherein patients were randomized 1:1:1 to APRO 12.5 mg, 25 mg, or PBO. A 32-week single-blind period on APRO 25 mg followed. Patients were then re-randomized 1:1 to APRO 25 mg or PBO in a 12-week withdrawal period. The primary endpoint was change from baseline to Week 4 in mean trough SBP. Changes in SBP from withdrawal baseline (Week 36) to Week 40 and in 24-hour, daytime (09:00-21:00), and nighttime (01:00-06:00) ambulatory BP monitoring (ABPM) measures at Weeks 4 and 40 were also assessed. Results: Eighty-two of 730 patients (11.2%) were Black (APRO 12.5 mg, n = 28; 25 mg, n = 28; PBO, n = 26). At Week 4, APRO and PBO produced similar office SBP reductions (least squares mean difference from PBO, 12.5 mg: 0.63 mmHg; 25 mg: 0.12 mmHg). However, APRO produced pronounced reductions vs PBO in mean 24-hour (12.5 mg: –3.23 mmHg; 25 mg: –7.85 mmHg), daytime (12.5 mg: –6.16 mmHg; 25 mg: –9.13 mmHg), and nighttime (12.5 mg: –2.63 mmHg; 25 mg: –8.53 mmHg) ambulatory SBP. Four weeks after withdrawal, office SBP increased with PBO vs APRO 25 mg (difference: +9.87 mmHg), which was confirmed with ambulatory SBP (difference, 25 mg; 24-hour: +8.13 mmHg, daytime: +3.39 mmHg, nighttime: +9.70 mmHg). Safety in Black patients was comparable to the overall population, with no new signals. During the double-blind period, treatment-emergent adverse events were reported in 6/28 (21.4%), 9/29 (31.0%), and 4/25 (16.0%) patients with APRO 12.5 mg, APRO 25 mg, and PBO. Edema or fluid retention occurred in 3/29 patients (10.3%) on APRO 25 mg, and no patients on APRO 12.5 mg or PBO. Conclusion: APRO was well tolerated and produced clinically relevant reductions in SBP by ABPM in Black patients.