Aprocitentan has proved itself a promising new agent for blood pressure control. In the 730-patient PRECISION trial, aprocitentan (Idorsia Pharmaceuticals) lowered both office and 24-hour ambulatory BP among people with resistant hypertension.
Clinicians usually treat resistant hypertension with the general diuretic spironolactone, which targets the renin-angiotensin-aldosterone system. But aprocitentan, a dual endothelin receptor antagonist, works on the endothelin pathway – a previously untapped avenue to BP control.
PRECISION was a blinded, randomized, placebo-controlled, phase 3 trial conducted in Europe, Asia, Australia, and North America. The study consisted of three consecutive parts:
- In part 1, patients were randomized to take either 12.5 or 25 mg aprocitentan, or placebo, for four weeks.
- In part 2, all patients took aprocitentan 25 mg for 32 weeks.
- In part 3, patients were rerandomized to aprocitentan 25 mg or placebo for 12 weeks.
At the end of part 1, patients who took 12.5 and 25 mg aprocitentan saw the following placebo-adjusted blood pressure drops:
- Office systolic BP decreased by 3.8 and 3.7 mmHg
- Office diastolic BP decreased by 3.9 and 4.5 mmHg
- 24h ambulatory systolic BP dropped by 4.2 and 5.9 mmHg
By the end of part 2, patients showed sustained BP reduction for all 32 weeks.
At the end of part 3, BP rose in patients who had switched from taking 25 mg aprocitentan to placebo. For those who continued taking aprocitentan, their reduced BP level was maintained.
Edema was the most common side effect during the initial four weeks (9.1% w/ 12.5 mg, 18.4% w/ 25 mg), although the authors said this could be easily managed with diuretics.
Notably, the Lancet reviewers held a more skeptical view, questioning whether the result was clinically significant, especially in light of the high rate of edema. They conclude that the utility of aprocitentan remains unclear, particularly compared to existing options like spironolactone.
This appears to be a win for aprocitentan, especially since it offers a novel mechanism for BP reduction in patients with resistant hypertension, even if more research is needed to know for sure.