Abstract FR606: The effect of aprocitentan in patients with very high blood pressure at baseline

Background: Sustained elevated blood pressure (BP) markedly increases the risk of stroke, heart failure, kidney disease, and cardiovascular death. Thus, reducing BP is clinically critical, especially for patients with RHT, who remain at exceptionally high cardiovascular and renal risk despite multiple therapies. Aprocitentan, a newly approved dual endothelin receptor antagonist, offers a novel therapeutic option for these patients. This post hoc analysis aims to evaluate the effect of aprocitentan in patients with Grade 2 Hypertension (HTN) at baseline (160 to 179 mmHg). Methods: In PRECISION, patients with office systolic BP (SBP) ≥140 and <180 mmHg despite being treated with standardized background therapy of 3 antihypertensive drugs were initially randomized to receive aprocitentan (12.5 mg or 25 mg daily) or placebo for 4 weeks in Part 1, followed by a 32-week single-blind Part 2. BP was measured at trough. Here patients from PRECISION with Grade 1 (BL SBP <160 mmHg) and Grade 2 HTN (BL SBP ≥160 mmHg and <180 mmHg) were evaluated. Of the 730 patients, 23.4% (n=171) had Grade 2 HTN. Results: The baseline characteristics of both groups were similar (Table 1). At Week 2, the Grade 2 HTN group showed a mean reduction (SD) in SiSBP of 22.3 (13.7) mmHg and 21.8 mmHg (15.1) in the aprocitentan 12.5mg and 25mg arms, respectively (Placebo: 14.3 mmHg (16.8)). At week 4, this group showed a mean reduction (SD) in SiSBP of 22.5 mmHg (13.6) and 19.9 mmHg (16.1) in the aprocitentan 12.5mg and 25mg arms, respectively (Placebo: 18.9 mmHg (16.5)). This reduction was maintained at Week 36. The mean reduction in 24-hour ambulatory SBP, daytime and nighttime SBP at week 4 were significant and similar in both groups. At week 4, a higher reduction in UACR (urine albumin-creatinine ratio) was observed in the Grade 2 HTN group, i.e. 32% and 44% in the aprocitentan 12.5 mg and 25 mg arms, respectively (compared to reduction in the Grade 1 HTN group: 26% and 27% in the aprocitentan 12.5 mg and 25 mg arms). At Week 36, the reduction in UACR was similar in both groups. The incidence of treatment emergent edema, which was transient in nature, was comparable in both groups (Grade 2 HTN patients: 12.3% aprocitentan 12.5mg, 20.7% aprocitentan 25mg and 5.6% placebo), with peripheral edema being the most common. Conclusions: This analysis suggests that aprocitentan is effective and well-tolerated in patients with very high blood pressure, with a rapid onset of action by Week 2.