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Aldosterone synthase inhibitors in uncontrolled and resistant hypertension: A phenotype-stratified systematic review and network meta-analysis of randomized trials.
This systematic review and network meta-analysis pooled randomized trials of aldosterone synthase inhibitors (ASIs) for people with resistant or uncontrol…
Signal score47Research triage score
CertaintyLowVerify in full text
PMID42234700Source identifier
Research triage, not medical advice
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Plain-English signal
This systematic review and network meta-analysis pooled randomized trials of aldosterone synthase inhibitors (ASIs) for people with resistant or uncontrolled high blood pressure. Across seven trials (2,828 participants), the ASIs baxdrostat, lorundrostat, and LCI699/osilodrostat lowered systolic blood pressure compared with placebo (largest reported reductions roughly 5-9 mmHg depending on agent). In resistant hypertension, lorundrostat and baxdrostat showed pronounced reductions; in the uncontrolled group, osilodrostat had a large point estimate but came from a single early-phase trial. Use of ASIs was associated with higher risks of hypotension, high potassium (hyperkalemia), and low sodium (hyponatremia). The authors conclude ASIs can meaningfully lower BP but note short-term electrolyte and blood-pressure risks and call for outcome-driven and longer-term safety studies.
Why it matters
- Addresses treatment options for resistant and uncontrolled hypertension, conditions with high cardiovascular risk and limited effective options.
- Evaluates aldosterone synthase inhibitors (ASIs) - a mechanistically targeted drug class - across phenotypes (resistant vs uncontrolled), which could inform phenotype-specific prescribing or trial design.
- Reports both efficacy (SBP/DBP reductions) and safety signals (hypotension, hyperkalemia, hyponatremia) that are directly relevant to clinical monitoring and risk-benefit considerations.
Primary outcomes
- Systolic blood pressure (SBP) change
- Diastolic blood pressure (DBP) change
- Safety outcomes: hypotension, hyperkalemia, hyponatremia, serious adverse events, discontinuation
Effect summary
Across 7 RCTs (n = 2,828), ASIs reduced SBP versus placebo: baxdrostat ~-8.63 mmHg, lorundrostat ~-7.47 mmHg, LCI699/osilodrostat ~-5.63 mmHg; DBP reductions significant for baxdrostat and lorundrostat. In phenotype subgroups, lorundrostat and baxdrostat had larger reductions in resistant hypertension; osilodrostat had a large point estimate in uncontrolled hypertension from a single early-phase trial. Safety: increased risks of hypotension (RR 2.67), hyperkalemia (RR 7.94), and hyponatremia (RR 2.07); no increase in serious adverse events or discontinuation reported in the abstract.
Benefit-cost lens
| Quick take | ASIs lowered systolic and diastolic BP versus placebo across trials, but short-term electrolyte and hypotension risks were increased. Use this as a monitoring/prioritization signal; do not change practice without full-text review and outcome trials. |
|---|---|
| BCR anchor | 1 |
| Time horizon | 3 |
| Discount rate | 0.03 |
| Assumptions | Based solely on abstract and metadata; assumes reported BP and safety effect sizes are accurate and generalizable, but long-term outcome effects and broader population harms are unknown. |
Benefit-cost fields are assumptions-based unless explicitly source-derived. Treat them as prompts for deeper economic review.
Risk of bias
| Tool | rapid-abstract-screen |
|---|---|
| Verdict | Higher uncertainty |
| Notes | Assessment based only on abstract and metadata. Though the review pooled randomized trials and used network meta-analysis with consistency checks, details on study-by-study risk of bias, trial durations, blinding, and outcome adjudication are not available in the abstract and may affect confidence. |
Harms, equity, conflicts & implementation
| Implementation | Full-text review for trial inclusion, durations, dosing, monitoring protocols, and subgroup definitions; local feasibility and cost assessment for drug availability and laboratory monitoring; clinician and patient education on electrolyte monitoring. |
|---|---|
| Equity impact | Unclear from abstract; equity considerations depend on differential access to novel ASIs, monitoring capacity for electrolyte disturbances, and whether trial populations reflect underserved groups. |
| Harms | Abstract reports increased risks of hypotension, hyperkalemia, and hyponatremia. Full-text needed to quantify absolute risks, timing, severity, and reversibility. |
| Registration | PROSPERO CRD420251266257 |
| Replication | Unknown from automated PubMed triage; authors pooled 7 RCTs but independent replication and long-term outcome studies are needed. |
Source links — verify original
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