Second-Generation Aldosterone Synthase Inhibitors for Hypertension
Pooled result · Systolic blood pressure (SBP)MD −6.7 mm Hg 95% CI −8.78 to −4.59- Bayesian meta-analysis of randomized controlled trials
- Bayesian random-effects model
- Bayesian binomial-normal hierarchical model
+2 more
- Bayesian random-effects model
- Bayesian binomial-normal hierarchical model
Authors' conclusion
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.
Study context
- Population
- Patients with hypertensionEight randomized controlled trials (RCTs), 2,430 [72%] randomized to ASI
- Participants
- 3,369 patients
- Comparison
- ASI compared with placebo
- ASIn = 2,430
Pooled result
Systolic blood pressure (SBP)
MD
−6.7 mm Hg
95% CI −8.78 to −4.59
ASI vs placebo
MD −6.7 mm Hg (95% CI −8.78 to −4.59)
As reported in the abstract
Further pooled results
| Outcome | MD (mm Hg) (95% CI) | |
|---|---|---|
| Diastolic blood pressure · τ2 1.44 | −2.09 (−3.68 to −0.44) | |
| −4−202Difference, mm Hg (linear scale) |
| Outcome | OR (95% CI) | |
|---|---|---|
| Hypertensive urgency · τ2 0.07 | 0.36 (0.13–0.90) | |
| All-cause mortality · τ2 0.10; no difference | 0.45 (0.06–3.20) | |
| 0.050.21520Odds ratio (log scale) |
Probability of clinically meaningful reduction in systolic blood pressure (SBP) (MD < −5 mm Hg) (subgroup)
- baxdrostat
- 87.5%
- lorundrostat
- 94.3%
Safety
| Outcome | OR (95% CI) | |
|---|---|---|
| Adrenal insufficiency · τ2 0.3; no difference | 0.5 (0.1–3.1) | |
| Hyperkalemia · τ2 0.23 | 7.1 (3.56–15.2) | |
| Hyponatremia · τ2 0.1 | 2.6 (1.25–5.98) | |
| Hypotension · τ2 0.1 | 3.28 (1.43–8.16) | |
| 0.050.21520Odds ratio (log scale) |
Original publication
Second-Generation Aldosterone Synthase Inhibitors for Hypertension. JACC Adv. Published 27 February 2026. doi:10.1016/j.jacadv.2026.102621
Summarised from the published abstract; every number is checked against it