Baxdrostat in Resistant and Uncontrolled Hypertension: A Systematic Review and Meta-Analysis

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• Picked for Nephrology (top studies of the week, 11 October 2026): Baxdrostat efficacy and safety in resistant hypertension

Abstract

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 mmHg, 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 mmHg; 95% CI, -10.25 to -3.55; P < 0.0001), with high heterogeneity (I2 = 74%). Numerically larger reductions were observed at higher doses: the 2 mg dose yielded the largest reduction (MD -8.16 mmHg; P < 0.00001; I2 = 45%), followed by 1 mg (MD -6.06 mmHg; P = 0.010), while 0.5 mg was non-significant (P = 0.14). Baxdrostat increased the odds of achieving SBP < 130 mmHg (OR 2.70; P = 0.01), although the magnitude of this effect varied substantially across trials (I² = 89%). DBP reduction was significant at the 2 mg dose (MD -3.51 mmHg; P < 0.0001) and the 1 mg dose (MD -2.55 mmHg; 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 reductions in systolic blood pressure among various hypertensive populations, increasing the likelihood of achieving blood pressure targets (SBP < 130 mmHg), although the magnitude of this effect varied substantially across trials (I² = 89%). 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.

Abstract as published, via PubMed.