Blood Pressure Control With Aprocitentan in Resistant Hypertension

Objective: The results of the phase 3 PRECISON study demonstrated that in patients with resistant hypertension, aprocitentan in addition to a fixed-dose combination of amlodipine, valsartan, hydrochlorothiazide was well tolerated and superior to placebo in lowering blood pressure at week 4 with a sustained effect at week 40. This pre-planned analysis evaluates the % of subjects with controlled blood pressure according to hypertension guidelines at different timepoints during the study. Design and method: In PRECISION, the mean SiSBP and SiDBP were 153 mmHg and 88 mmHg at baseline, across groups. In the 4-week DB part 1, patients were randomized to aprocitentan 12.5 mg, 25 mg and placebo. Thereafter all patients received 25 mg aprocitentan during the SB part 2. At week 36, subjects were re-randomized to 25 mg or placebo up to week 48. The primary endpoint was at week 4 and the key secondary endpoint at week 40. Control was defined as SiSBP <140 or <135 and/or SiDBP < 90 or <85 mm/Hg (trough unattended office BP). The % of patients achieving control was calculated at the end of part 1 (week 4, primary end point), end of part 2 (week 36) and at the timepoint of the key secondary endpoint (week 40). Results: At week 4, more patients had SiSBP below 140 mmHg with 12.5 mg (56%) and 25 mg (57%) compared to placebo (44%). The % of patients with controlled SiSBP increased to 64% at the end of part 2 and reached 67% of patients treated with 25 mg during part 3. The % of patients achieving control decreased in those re-randomized to placebo (48%). A similar trend was observed when the threshold of 135 mmHg was considered, with 56% of patients achieving control at week 40 with 25 mg, while in patients re-randomized to placebo the control rate was 35%. 52 to 65% of patients had both SiSBP and SiDBP controlled with aprocitentan 25 mg at week 40. Conclusions: Aprocitentan controlled systolic and diastolic blood pressure in up to 67% and 90% respectively, of patients with resistant hypertension.