EFFECTS OF THE DUAL ENDOTHELIN ANTAGONIST APROCITENTAN ON AMBULATORY BLOOD PRESSURE INDICES IN PATIENTS WITH RESISTANT HYPERTENSION. RESULTS FROM THE PRECISION STUDY

Abstract

Objective: The phase-3 PRECISION trial demonstrated both the safety and the efficacy of aprocitentan to lower office blood pressure (BP) in patients with resistant hypertension. Here, we report on the effects on relevant indices of ambulatory BP measurements (ABPM). Design and method: A total of 730 patients with resistant hypertension were randomized to aprocitentan 12.5 mg (n = 243), 25 mg (n = 243), or placebo (n = 244). Paired ABPM results at baseline and week 4 of double-blind treatment were available for n = 174, n = 182, and n = 178 patients, respectively. Changes in 24h ABPM from baseline to week 4 were pre-defined as a secondary endpoint. Here, we analyzed effects on 24h average BP, daytime BP, night-time BP, nocturnal dipping, and BP load. Statistical significance was assessed using the Wilcoxon rank-sum test. Results: At week 4, after placebo correction, aprocitentan decreased 24-hour ambulatory SBP (-4.2 mmHg; 95% CI: –6.2, –2.1 for the 12.5-mg dose and –5.9 mmHg; 95% CI: –7.9, –3.8 for the 25-mg dose). The placebo-corrected SBP-lowering was more pronounced during night-time (–5·1 and –7·4 mmHg) compared with daytime (–3·8 and –5·3mmHg) for the 12.5 and 25mg doses, respectively. At baseline, non-dipper rates were 66%, 62%, and 60% for the 12.5mg, 25mg of aprocitentan, and placebo groups, respectively. Non-dippers had a particularly pronounced reduction in night-time systolic BP compared with dippers for both 12.5mg (-11.25 vs -2.79mmHg; p < 0.01) and 25mg of aprocitentan (-13.12 vs -6.29mmHg; p < 0.01). After 4 weeks of treatment, the proportion of non-dippers who had normalization of their dipping pattern was 44%, 40% and 31% for 12.5mg, 25mg of aprocitentan, and placebo, respectively. The change in BP load for both daytime and night-time was more pronounced with both doses of aprocitentan (-18.7/-24.5% for 12.5mg; -20.7/-21.1% for 25mg) compared to placebo (-9.2/-6.6 %; p < 0.001 for all comparisons). Conclusions: In patients with resistant hypertension, aprocitentan resulted in substantial ambulatory BP lowering, particularly during night-time. This was associated with reduction in non-dipping rates and BP load. These findings further support the likely clinical benefit of aprocitentan in resistant hypertension.