Abstract P442: Impact of arterial stiffness on the blood pressure lowering effect of the dual endothelin antagonist aprocitentan in patients with resistant hypertension

Abstract

Background: The phase-3 PRECISION study demonstrated the efficacy of aprocitentan to lower both office and ambulatory blood pressure (BP) in patients with resistant hypertension. Increased arterial stiffness has been associated with less favorable responses to pharmacologic BP lowering therapies. In this post-hoc analysis, we investigated the impact of arterial stiffness, assessed by the ambulatory arterial stiffness index (AASI), on the BP lowering effect of aprocitentan. Methods: The study included a 4-week double blind period (aprocitentan 12.5 mg, 25 mg, or placebo) and a 32-week single blind period (aprocitentan 25 mg). A total of 730 patients with resistant hypertension were randomized and 633 had available ambulatory BP monitoring (ABPM) results at baseline. The AASI was calculated from ABPM data as 1 minus the regression slope of diastolic on systolic BP. The patient population was dichotomized into two groups according to the baseline median AASI. Results: Patients with higher baseline AASI (≥0.54) tended to be older (63±11 versus 60±10) and to have a higher 24-hour ambulatory systolic BP (140±14 versus 135±14 mmHg) than patients with lower AASI (<0.54). These patients with higher baseline AASI were also more likely to have chronic kidney disease stage 3-4 corresponding to an estimated glomerular filtration rate in the 15 to 60 mL/min/1.73 m 2 range (27% versus 18%). The BP lowering effect of aprocitentan at Week 4 was similar for both the patients with stiffer vasculature who have a higher baseline AASI (≥0.54) and for those with a lower AASI (<0.54) (Table 1). No relevant change in AASI was reported with aprocitentan treatment at Week 4 (end of the double-blind period) or Week 36 (end of the single-blind period). Conclusion: Aprocitentan is an effective BP lowering therapy across the arterial stiffness continuum observed in patients with resistant hypertension. Longer observation times are needed to fully assess the impact of treatment on this structural and functional parameter.