Aprocitentan lowers blood pressure without serious adverse effects

The dual endothelin receptor antagonist aprocitentan reduces blood pressure (BP) at doses of 10 to 25 mg without producing serious adverse effects, according to the results of a dose-response study.

The study randomized 490 patients with a sitting diastolic BP of 90–109 mm Hg to receive aprocitentan at 5, 10, 25 or 50 mg, placebo, or lisinopril 20 mg as a positive control. Treatment was given once daily for 8 weeks. Multiple automated office BP readings were taken as patients rested unattended (unattended automated office BP).

A total of 409 patients completed 8 weeks of therapy. Aprocitentan at higher doses yielded reductions in unattended automated office BP. Specifically, the 10-, 25- and 50-mg doses lowered sitting systolic/diastolic unattended automated office BP by 7.05/4.93, 9.90/6.99 and 7.58/4.95 mm Hg, respectively, compared with placebo (p≤0.014). On the other hand, lisinopril 20 mg produced a reduction of 4.84/3.81 mm Hg relative to placebo.

In the group of patients with valid ambulatory BP, the placebo-corrected 24-hour BP reductions were 3.99/4.04 mm Hg with aprocitentan 10 mg, 4.83/5.89 mm Hg with the 25-mg dose, and 3.67/4.45 mm Hg with the 50-mg dose.

Incidence of adverse events did not differ in the aprocitentan groups (22.0–40.2 percent) and the placebo group (36.6 percent). Relative to placebo, aprocitentan was associated with dose-dependent decreases in haemoglobin, haematocrit, albumin and uric acid, as well as an increase in estimated plasma volume, but no change in weight.

According to the researchers, aprocitentan doses of 12.5 and 25 mg were selected for further investigation in hypertension.