Abstract 2584: Darusentan Significantly Reduces Systolic Blood Pressure in Patients with Resistant Hypertension on 4 or More Antihypertensive Drugs
Purpose: Patients with resistant hypertension (RHTN) as defined by JNC 7 guidelines do not achieve recommended systolic blood pressure (SBP) goals despite treatment with multidrug antihypertensive regimens. Darusentan is an ETA-selective endothelin receptor antagonist that has demonstrated significant decreases in trough cuff SBP and 24-hr ambulatory SBP in a Phase 2 dose-ranging study in patients with RHTN receiving full doses of ≥3 antihypertensive drugs (AHD). The purpose of this post hoc subanalysis was to assess the effects of darusentan according to the number of AHD received at baseline.
Methods: In the Phase 2 double-blind, placebo-controlled, multicenter, dose-ranging study, 115 RHTN subjects underwent a 2-wk placebo run-in, followed by 2:1 randomization of oral darusentan or placebo for 10 wks. Darusentan was initiated at 10 mg/day and was up-titrated every 2 wks, through doses of 50, 100, and 150 mg, until a maximum dose of 300 mg was achieved. The primary endpoint of the study examined change from baseline in trough sitting SBP. Secondary endpoints included change from baseline in diastolic blood pressure (DBP), 24-hr ambulatory SBP, and percentage of subjects achieving guideline-recommended SBP goal. P values were unadjusted for multiple comparisons.
Results: Of the 115 subjects, 64 were on 3 AHD and 51 were on ≥4 AHD at baseline. At week 10 of darusentan treatment (300 mg dose), the placebo-corrected change from baseline in trough sitting SBP was -9.39 mmHg (p=0.03) in the subjects on exactly 3 AHD and -12.71 mmHg (p=0.007) for subjects on ≥4 AHD. Although not powered to demonstrate statistical significance, the percentage of subjects achieving SBP goal or a decrease in SBP of at least 10 mmHg as compared to baseline values, was 76% on darusentan at week 10 versus 57% in the placebo group (p=0.11) in the subjects on exactly 3 AHD, and was 66% versus 38% on placebo (p=0.06) in the subjects on ≥4 AHD.
Conclusions: Darusentan significantly reduces SBP and may allow more RHTN patients to achieve guideline-recommended SBP goals when added to a regimen that includes exactly 3 or ≥4 antihypertensive drugs. Darusentan may be useful for reducing SBP in patients with RHTN independent of the number of background antihypertensive drugs.