A new drug-level network meta-analysis including 10 RCTs and 2,865 patients provides an interesting perspective on therapies targeting the aldosterone-related sodium-retention pathway.

Compared with placebo, office systolic BP was reduced by:

Amiloride: −14.08 mmHg

Spironolactone: −10.78 mmHg

Baxdrostat: −9.09 mmHg

Eplerenone: −8.14 mmHg

Lorundrostat: −6.80 mmHg

But the key message is not the ranking of drugs. These are network estimates, not head-to-head comparisons.

The real message is the pathway:

Aldosterone synthesis → Mineralocorticoid receptor → ENaC → Sodium retention

Different therapies intervene at different points, but share a common therapeutic goal.

MRAs remain the established reference add-on therapy, while aldosterone synthase inhibitors and amiloride are expanding the possibilities for pathway-directed treatment.

Perhaps the question in resistant hypertension is evolving from “Which fourth drug should we add?” to “Which component of aldosterone-driven sodium retention should we target?”

Different mechanisms. Same pathophysiological axis.

1. Tsou Y-L et al. J Clin Hypertens. 2026;28:e70365.