Nieuwe aldosteronsynthase-remmers bij hypertensie: Bayesiaanse meta-analyse

BACKGROUND: Second-generation aldosterone-synthase inhibitors (ASIs) may offer a novel treatment for hypertension. OBJECTIVES: The objective of the study was to assess the efficacy and safety of ASIs in this clinical setting. METHODS: We searched major databases for randomized controlled trials assessing ASIs (baxdrostat, lorundrostat, and vicadrostat) in patients with hypertension. For efficacy outcomes, mean differences (MD) with 95% credible intervals (CrIs) were estimated using a Bayesian random-effects model. For adverse events, OR with 95% CrI were estimated using a Bayesian binomial-normal hierarchical model. The protocol was registered in Prospective Register of Systematic Reviews (CRD420251132306). RESULTS: Eight randomized controlled trials were included (n = 3,371; 2,430 [72%] randomized to ASI). ASI reduced systolic blood pressure (SBP) (MD: -6.7 mm Hg; CrI: -8.78, -4.59; τ2 3.24), diastolic blood pressure (MD: -2.09 mm Hg; CrI: -3.68, 0.44; τ2 1.44), and hypertensive urgency (OR: 0.36; CrI: 0.13, 0.90; τ2 0.07) compared with placebo. There was no difference in all-cause mortality (OR: 0.45; CrI: 0.06, 3.20; τ2 0.10) or adrenal insufficiency (OR: 0.5; CrI: 0.1, 3.0; τ2 0.3) between groups. However, ASIs increased the odds of hyperkalemia (OR: 7.1; CrI: 3.56, 15.2; τ2 0.23), hyponatremia (OR: 2.6; CrI: 1.25, 5.98; τ2 0.1), and hypotension (OR: 3.28; CrI: 1.43, 8.16; τ2 0.1). In subgroup analysis, the probability of achieving a clinically meaningful reduction in SBP (MD <5 mm Hg) was 87.5% with baxdrostat and 94.3% with lorundrostat. CONCLUSIONS: Second-generation ASIs had a high likelihood of a clinically significant reduction in SBP compared with placebo. However, hyperkalemia, hyponatremia, and hypotension were more frequent with ASIs.