Can baxdrostat redefine blood pressure control in resistant and uncontrolled hypertension? a systematic review, meta-analysis, and trial sequential analysis

Resistant hypertension remains a major clinical challenge despite multidrug therapy. Baxdrostat, a highly selective aldosterone synthase inhibitor, has emerged as a novel treatment option. We conducted an updated systematic review and meta-analysis to evaluate its efficacy and safety. PubMed, Embase, Scopus, Cochrane Library, and ClinicalTrials.gov were searched through April 30, 2026, for randomized controlled trials comparing baxdrostat with control in uncontrolled or resistant hypertension. Random-effects meta-analyses, Trial Sequential Analysis (TSA), subgroup/sensitivity analyses, risk of bias, and GRADE evaluations were performed. Baxdrostat significantly reduced seated systolic blood pressure (SBP) overall (MD: − 6.69 mmHg, 95% CI: − 9.30 to − 4.07; p < 0.00001) and in the resistant hypertension subgroup. Significant reductions were also observed in seated diastolic, 24-h ambulatory, and night-time ambulatory SBP (all p < 0.001), leading to higher achievement of target BP < 130 mmHg. Mechanistically, baxdrostat significantly increased hyperkalemia risk (RR: 3.84, 95% CI: 1.82 to 8.11) and serum potassium elevations > 5.5 and > 6.0 mmol/L. Crucially, severe hyperkalemia (6.5 mmol/L) did not increase significantly. While overall adverse events were more frequent, serious adverse events, hypotension, hyponatremia, mortality, and discontinuation due to hyperkalemia were comparable between groups. TSA confirmed conclusive evidence for SBP reduction. Baxdrostat, particularly at 2 mg, provides clinically meaningful BP reductions. Anticipated potassium elevations (> 5.5 and > 6.0 mmol/L) serve as a safety signal requiring cautious monitoring, but the absence of significant severe hyperkalemia (> 6.5 mmol/L) highlights a reassuring safety profile. Serious safety outcomes remain entirely comparable to control.