Impact of Relacorilant on Blood Pressure and Antihypertensive Medication Burden in Patients With Hypercortisolism and Hypertension: Results From the GRACE Study

Abstract

In the phase 3 GRACE study (NCT03697109) in adults with endogenous hypercortisolism and hypertension, hyperglycemia, or both, relacorilant significantly improved blood pressure (BP), meeting the primary endpoint. We report on the impact of relacorilant on BP and antihypertensive medication use among study participants with hypertension. GRACE comprised a 22-week, open-label (OL) phase of relacorilant 100–400 mg once daily followed by a 12-week, double-blind, placebo-controlled randomized withdrawal phase. Hypertension was defined as mean systolic blood pressure (SBP) 135–170 mm Hg and/or diastolic blood pressure (DBP) 85–110 mm Hg. Among participants with hypertension at OL baseline (n=102), mean SBP and DBP were 141 and 89 mm Hg, respectively, and 76% (78/102) were taking ≥1 antihypertensive medication. The most common (≥15%) antihypertensive classes were calcium channel blockers (31%), angiotensin-converting enzyme (ACE) inhibitors (26%), angiotensin II receptor blockers (ARBs) (25%), beta blockers (22%), and aldosterone antagonists (20%). Relacorilant significantly improved BP from baseline to week 22 (P<0.0001), and 19% (15/78) of those taking antihypertensive medications discontinued and/or decreased use by week 22 or their early termination visit. Medication reductions were most common with aldosterone antagonists (10%) and ARBs (8%). Complete discontinuation was highest for loop diuretics (31%) and calcium channel blockers (19%), followed by aldosterone antagonists (10%), ACE inhibitors (7%), beta blockers (5%), and ARBs (4%). In summary, in GRACE, relacorilant improved BP and resulted in antihypertensive medication decreases/discontinuations for participants with hypertension.