Baxdrostat Efficacy and Safety in Resistant and Uncontrolled Hypertension: A Meta-Analysis

Background: Aldosterone dysregulation is becoming more widely acknowledged as a key factor in resistant hypertension. Baxdrostat, a highly selective aldosterone synthase inhibitor that shows a 100:1 preference for CYP11B2 over CYP11B1, has been tested in various randomized controlled trials involving different hypertensive groups. We carried out a systematic review and meta-analysis to assess the efficacy and safety of baxdrostat for treating resistant hypertension. Methods: We included randomized, double-blind, placebo-controlled trials of baxdrostat in adults with hypertension from inception through March 2026. The primary outcome was the placebo-corrected change in seated systolic blood pressure (SBP). Secondary outcomes included the change in diastolic blood pressure (DBP), the proportion of patients achieving seated SBP <130 mm Hg, and the incidence of hyperkalemia and other adverse events. Results: Five trials (N=1,730) were included: BrigHTN, HALO, BaxHTN, FigHTN, and Bax24. Baxdrostat significantly reduced seated SBP vs. placebo (MD -6.90 mm Hg ; P<0.0001), with high heterogeneity (I2=74%). A dose-response was evident: the 2 mg dose yielded the largest reduction (MD -8.16 mm Hg; P<0.00001; I2=45%), followed by 1 mg (MD -6.06 mm Hg; P=0.01), while 0.5 mg was non-significant (P=0.14). Baxdrostat increased the odds of achieving SBP <130 mm (OR 2.70; P=0.01), although the magnitude of this effect varied substantially across trials (I 2 = 89%). DBP reduction was significant at the 2 mg dose (MD -3.51 mm Hg; P<0.0001) and the 1 mg dose (MD -2.55 mm Hg; P=0.03). Safety analysis showed higher odds of hyperkalemia (8.9% vs. 1.2%; OR 5.98; P = 0.008), with potassium >6.0 mmol/L in 3.8% of baxdrostat-treated patients versus 0.2% with placebo. Serious adverse events were not significantly increased (OR 1.35; P = 0.37). No deaths were attributable to baxdrostat. Conclusions: Baxdrostat produces statistically significant, dose-dependent reductions in systolic blood pressure among various hypertensive populations, increasing the likelihood of achieving blood pressure targets. Hyperkalemia was the principal safety concern but was not associated with serious clinical sequelae in the included trials. These findings support further investigation of aldosterone synthase inhibition as a therapeutic strategy for resistant and uncontrolled hypertension, with definitive clinical positioning awaiting results from ongoing cardiovascular and renal outcomes trials.