In the PRECISION trial of patients with resistant hypertension, the dual endothelin antagonist aprocitentan was “well tolerated and superior to placebo in lowering blood pressure,” researchers report.
The multicenter, blinded, randomized, parallel-group, phase 3 study included patients with sitting systolic blood pressure of 140 mm Hg or higher despite taking standardized background therapy with 3 antihypertensive drugs, including a diuretic, at centers in Europe, North America, Asia, and Australia. The study consisted of 3 parts, with double-blind aprocitentan 12.5 mg, aprocitentan 25 mg, or placebo for 4 weeks during part 1; single-blinded aprocitentan 25 mg for 32 weeks during part 2; and double-blind aprocitentan 25 mg or placebo for 12 weeks during part 3.
Based on primary and key secondary endpoints of changes in unattended office systolic blood pressure from baseline to week 4 and from withdrawal baseline to week 40, respectively, the researchers found the following: “The least square mean (SE) change in office systolic blood pressure at 4 weeks was –15.3 (SE 0.9) mm Hg for aprocitentan 12.5 mg, –15.2 (0.9) mm Hg for aprocitentan 25 mg, and –11.5 (0.9) mm Hg for placebo, for a difference versus placebo of –3.8 (1.3) mm Hg (97.5% CI –6.8 to –0.8, P = 0.0042) and –3.7 (1.3) mm Hg (–6.7 to –0.8; P = 0.0046), respectively. The respective difference for 24 h ambulatory systolic blood pressure was –4.2 mm Hg (95% CI –6.2 to –2.1) and –5.9 mm Hg (–7.9 to –3.8). After 4 weeks of withdrawal, office systolic blood pressure significantly increased with placebo versus aprocitentan (5.8 mm Hg, 95% CI 3.7 to 7.9, P <0.0001). The most frequent adverse event was mild-to-moderate oedema or fluid retention, occurring in 9%, 18%, and 2% for patients receiving aprocitentan 12.5 mg, 25 mg, and placebo, during the 4-week double-blind part, respectively. This event led to discontinuation in seven patients treated with aprocitentan. During the trial, a total of 11 treatment-emergent deaths occurred, none of which were regarded by the investigators to be related to study treatment.”