Abstract 13836: Percentage of Patients Achieving Blood Pressure Goals With Aprocitentan, a Dual Endothelin Receptor Antagonist: Results From a Randomized, Controlled Phase 3 Study (PRECISION)

Abstract

Background: In the phase 3 PRECISION trial, aprocitentan (APRO) lowered BP in patients with resistant hypertension. Research Question: How effective is APRO for achieving the following BP goals over 4 weeks: mean 24-hour ambulatory BP monitoring (ABPM) measurements <130/80 mmHg, daytime ABPM <135/85 mmHg, nighttime ABPM <120/70 mmHg, reduction in 24-hour ABPM ≥5 mmHg, mean trough unattended automated office BP <130/80 mmHg, and reduction in office systolic BP (SBP) ≥10 mmHg? Aim: To evaluate percentages of patients achieving BP goals with APRO or placebo (PBO) after 4 weeks of treatment. Methods: Patients had sitting unattended automated office SBP ≥140 mmHg despite prescription of ≥3 antihypertensives of different classes in the year prior to enrollment. After 4 weeks of standardized triple 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 added to background therapy. We evaluated percentages of patients achieving BP goals during the double-blind period. Results: The APRO 12.5 mg, APRO 25 mg, and PBO groups comprised 243, 243, and 244 patients, respectively. Among 633 patients with ABPM data, 41.1%, 51.6%, and 29.6% in the APRO 12.5 mg, APRO 25 mg, and PBO groups had 24-hour mean ABPM <130/80 mmHg. Similarly, 47.4%, 52.7%, and 35.8% in the APRO 12.5 mg, APRO 25 mg, and PBO groups had daytime ABPM <135/85 mmHg; 37.9%, 44.0%, and 22.9%, respectively, had nighttime ABPM <120/70 mmHg. In the APRO 12.5 mg, APRO 25 mg, and PBO groups, 61.7%, 64.8%, and 39.7% had reductions in ABPM of ≥5 mmHg. Overall, 25.1%, 24.2%, and 16.5% in the APRO 12.5 mg, APRO 25 mg, and PBO groups achieved mean office BP <130/80 mmHg; 65.0%, 65.8%, and 55.8%, respectively, had reductions in office SBP of ≥10 mmHg. APRO was generally well tolerated. Edema or fluid retention occurred in 9%, 18%, and 2% of patients in the APRO 12.5 mg, 25 mg, and PBO groups, respectively, during the 4-week double-blind period. Conclusion: Greater proportions of patients receiving APRO versus PBO achieved BP goals at 4 weeks. Based on ABPM, treatment benefits with APRO showed dose-dependency, with a larger effect for APRO 25 mg.