- Question
- Does the dual endothelin antagonist aprocitentan lower systolic blood pressure in patients with resistant hypertension?
- Design
- Multicentre, randomised, blinded, parallel-group phase 3 trial conducted in hospitals and research centres in Europe, North America, Asia and Australia, with 730 patients randomised. It had three parts: a 4-week double-blind placebo-controlled part, a 32-week patient-blind part with aprocitentan 25 mg, and a 12-week double-blind randomised withdrawal part.
- Population
- Adults with resistant hypertension, with sitting office systolic blood pressure of 140 mm Hg or higher despite standardised background therapy with three antihypertensive drugs including a diuretic.
- Intervention
- Aprocitentan 12.5 mg or 25 mg once daily for 4 weeks.
- Control
- Matching placebo for the same 4 weeks; in the withdrawal part, patients were re-randomised to aprocitentan 25 mg or placebo.
- Primary outcome
- Change in unattended office systolic blood pressure from baseline to week 4.
- Results
- At 4 weeks, the difference versus placebo was -3.8 mm Hg (97.5% CI -6.8 to -0.8; p=0.0042) with 12.5 mg and -3.7 mm Hg (-6.7 to -0.8; p=0.0046) with 25 mg. For 24-h ambulatory systolic pressure the difference was -4.2 mm Hg (95% CI -6.2 to -2.1) and -5.9 mm Hg (-7.9 to -3.8), respectively. After 4 weeks of withdrawal, systolic pressure rose by 5.8 mm Hg with placebo versus aprocitentan (95% CI 3.7 to 7.9; p<0.0001).
- Safety
- The most frequent adverse event was mild-to-moderate oedema or fluid retention: 9% with 12.5 mg, 18% with 25 mg and 2% with placebo; it led to discontinuation in seven aprocitentan-treated patients. Eleven treatment-emergent deaths occurred, none judged by investigators to be related to study treatment.
- Conclusion
- In patients with resistant hypertension, aprocitentan was well tolerated and superior to placebo in lowering blood pressure at week 4, with a sustained effect through week 40.
- Why it matters
- It showed that blocking the endothelin pathway, which is not targeted by currently available antihypertensive drugs, provides additional blood pressure lowering in resistant hypertension.
Card generated automatically with AI from the abstract of the original publication and the trial registry; every figure was checked against those sources. It may contain errors: verify the data at the source before using it for clinical decisions.
Generated on October 14, 2026