# Lorundrostat (Aldosterone Synthase Inhibitor): Comprehensive Medical Review

> **Honest evidence-based assessment.** Lorundrostat is the second aldosterone synthase inhibitor with mature Phase 2/3 data. It is the most direct competitor to baxdrostat and the comparison matters: better selectivity ratio on paper, three positive trials, and a meaningfully larger Phase 3. The hyperkalemia signal is real and dose-dependent.

> **Cross-references:** - Hypertension Hub - baxdrostat aldosterone synthase inhibitor medical review — companion ASi review - aprocitentan dual endothelin antagonist resistant hypertension medical review - 2025 AHA expanded htn guideline analysis - MRA vs nsMRA vs aldo synthase inhib — class comparison in Cardiology folder

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## Executive Summary (TL;DR)

1.  **Lorundrostat is a selective aldosterone synthase inhibitor** developed by Mineralys Therapeutics (Radnor, PA) with a published selectivity ratio of approximately **374:1** for CYP11B2 (aldosterone synthase) over CYP11B1 (cortisol synthesis). This is **3-4 fold more selective than baxdrostat** (approximately 100:1), which should translate to lower cortisol-axis interference if the in vitro selectivity holds in vivo.

2.  **Three positive trials in hand.** Target-HTN Phase 2 (Laffin 2023 JAMA), Advance-HTN Phase 2 (Laffin 2025 NEJM), and **Launch-HTN Phase 3 (Saxena 2025 JAMA, n=1083)**. Launch-HTN is the largest single-trial dataset for any new HTN agent in this cycle and represents the most mature evidence package among the novel ASi class.

3.  **Launch-HTN Phase 3 — the headline result.** N=1083 patients on 2-5 background drugs. Pooled 50 mg lorundrostat group reduced office SBP by **−16.9 mmHg vs −7.9 mmHg placebo** at week 6, for a **placebo-corrected SBP reduction of −9.1 mmHg (95% CI −13.3 to −4.9, P\<0.001)**. Effect size on office SBP is similar to baxdrostat BaxHTN (approximately −9 mmHg).

4.  **Advance-HTN Phase 2 — the 24-h ABPM proof.** N=285 with 24-h ABPM as primary endpoint, double-blind, run-in to exclude pseudoresistance. Placebo-corrected 24-h SBP reduction **−7.9 mmHg (stable 50 mg) and −6.5 mmHg (dose-adjusted up to 100 mg)** at week 12. ABPM is the gold standard — this is the cleanest BP signal in the lorundrostat program.

5.  **Target-HTN Phase 2 dose-finding established 50 mg as the right dose.** N=200 (163 with suppressed renin + 37 with non-suppressed renin). Dose-ranging found **50 mg once daily** had the best efficacy/safety balance, with placebo-corrected SBP −9.6 mmHg. **The 100 mg dose did not give meaningfully better BP lowering** but increased the hyperkalemia signal — same dose-response pattern seen in baxdrostat BrigHTN.

6.  **Hyperkalemia signal is real but smaller than baxdrostat in CKD.** In Target-HTN, **6 of 200 patients had K+ \>6.0 mmol/L** that corrected with dose reduction or discontinuation. In Advance-HTN, **5% (stable 50 mg) and 7% (dose-adjusted) had K+ \>6.0**. In Launch-HTN, hyperkalemia discontinuation rates were very low (approximately 0.4%). **No CKD-specific Phase 2 (yet)** — the BAX-CKD style signal of 41% hyperkalemia in advanced CKD has no equivalent lorundrostat trial. This is a knowledge gap for nephrology.

7.  **No hard outcome trials. No HF trials. No DKD trials.** Same gap as baxdrostat. The cardiorenal hypothesis for the ASi class rests on extrapolation from MRA evidence (FIDELIO-DKD, FIGARO-DKD, FINEARTS-HF), not lorundrostat-specific outcome data.

The Honest Read for Clinical Practice

Lorundrostat is the most “complete” Phase 3 ASi package right now. Three trials, larger N, NEJM and JAMA pivotal publications, and a selectivity ratio that beats baxdrostat on paper. **The clinically meaningful difference between lorundrostat and baxdrostat is genuinely small** based on current data — both lower SBP by approximately 8-9 mmHg placebo-corrected, both have a hyperkalemia signal, both lack hard outcome data. **Where they diverge is the CKD safety database:** baxdrostat has BAX-CKD with the worrying 41% hyperkalemia rate; lorundrostat does not have an equivalent CKD-specific trial. Reasonable people can read this as either “lorundrostat is safer in CKD” or “lorundrostat just hasn’t been stressed yet.” The honest answer is the second one.

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## 1. Mechanism of Action

### 1.1 Aldosterone Synthase Inhibition — Class Background

CYP11B2 (aldosterone synthase) catalyzes the final three steps of aldosterone biosynthesis in zona glomerulosa: 11-beta-hydroxylation, 18-hydroxylation, and 18-oxidation of corticosterone. Its sister enzyme **CYP11B1 (11-beta-hydroxylase)** catalyzes cortisol synthesis in zona fasciculata. These two enzymes share **93% amino acid sequence homology** — the engineering challenge of the ASi class is finding a small molecule that blocks CYP11B2 without simultaneously blocking CYP11B1 and crashing cortisol production (which is what killed osilodrostat/LCI699 as an HTN drug).

The ASi class promises something MRAs cannot deliver: **lower aldosterone production at the source** rather than blocking the receptor. Theoretically this should: - Avoid the gynecomastia of spironolactone (no MR antagonism in androgen-target tissues) - Avoid the hyperkalemia ceiling of MRAs (less because aldosterone is reduced rather than fully blocked) - Reduce non-genomic aldosterone effects that bypass the MR (vascular fibrosis, endothelial dysfunction)

The reality is more nuanced. ASi drugs still cause hyperkalemia — just from a different mechanism (less aldosterone → less K+ excretion in the distal nephron). The “lower hyperkalemia” promise has not held up cleanly in CKD populations.

### 1.2 Lorundrostat-Specific Pharmacology

| Parameter | Value |
|----|----|
| Class | Selective CYP11B2 inhibitor (aldosterone synthase) |
| CYP11B2 / CYP11B1 selectivity ratio | **Approximately 374:1** (vs baxdrostat approximately 100:1) |
| Half-life | Approximately 10-12 hours |
| Dosing | Once daily (50 mg standard, 100 mg high) |
| Bioavailability | Oral, food-effect modest |
| Metabolism | Hepatic, multiple CYP pathways |
| Renal dose adjustment | Not yet defined (Launch-HTN required eGFR \>45) |
| Developer | Mineralys Therapeutics |

The **374:1 selectivity ratio** is the key marketing differentiator vs baxdrostat (100:1). Whether this translates to a meaningful clinical advantage on cortisol axis preservation requires comparing serum cortisol and ACTH measurements across trials — both BrigHTN and Target-HTN reported preserved cortisol with no clinical adrenal insufficiency events.

### 1.3 Lorundrostat Trial Eligibility and Investigational Status

Target-HTN was deliberately designed in two cohorts: - **Cohort 1 (n=163):** “Aldosterone-driven HTN” — suppressed plasma renin activity (PRA ≤1.0) AND elevated plasma aldosterone (≥1.0 ng/dL). This selects the patients most likely to respond. - **Cohort 2 (n=37):** “Non-suppressed renin” — confirms the drug works even without the ARR phenotype.

Both cohorts responded. The 100 mg dose in Cohort 2 reduced SBP by 11.4 mmHg (similar magnitude to Cohort 1). **This was a critical enrichment trial finding** because it showed lorundrostat does not require pre-screening with renin/aldosterone testing — meaning the drug can be deployed without lab gatekeeping.

    flowchart LR
        A[Cholesterol] --> B[Pregnenolone]
        B --> C[Progesterone]
        C --> D[Corticosterone]
        D --> E[CYP11B2<br/>Aldosterone Synthase]
        D --> F[CYP11B1<br/>11β-Hydroxylase]
        E --> G[Aldosterone]
        F --> H[Cortisol]
        I[Lorundrostat] -.blocks.-> E
        I -.minimal effect at therapeutic dose.-> F
        G -.suppression.-> J[Lower BP<br/>Lower K+ excretion]
        style I fill:#ffe066,color:#1a1a1a
        style J fill:#a3e4d7,color:#1a1a1a

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## 2. Clinical Evidence

### 2.1 Target-HTN — Phase 2 Dose-Ranging (Laffin et al., JAMA 2023, PMID 37690061)

| Cohort | Inclusion | N | Treatment Arms |
|----|----|----|----|
| 1 | Suppressed PRA (≤1.0 ng/mL/h) + elevated aldosterone (≥1.0 ng/dL) | 163 | Placebo or 1 of 5 lorundrostat doses (12.5, 50, 100 mg QD; 12.5 or 25 mg BID) |
| 2 | PRA \>1.0 ng/mL/h | 37 | Placebo or lorundrostat 100 mg QD (1:6 ratio) |

**Primary endpoint: change in automated office SBP at week 8.**

#### Cohort 1 Results

| Dose | SBP Change (mmHg) | Δ vs Placebo | 90% CI | P value |
|----|----|----|----|----|
| Placebo | −4.1 | reference | — | — |
| 12.5 mg QD | −6.9 | −2.8 | NS | NS |
| 50 mg QD | **−13.2** | **−9.6** | −15.8 to −3.4 | **0.01** |
| 100 mg QD | **−14.1** | not significant in pairwise | not significant | NS |
| 12.5 mg BID | −13.8 | similar to 50 mg QD | — | — |
| 25 mg BID | −10.1 | — | — | — |

**Key finding: 50 mg QD became the chosen dose** because it had the best efficacy/safety balance. The 100 mg arm did not achieve the primary endpoint despite numerically larger SBP reduction — likely a function of sample size and variability rather than true ceiling.

#### Cohort 2 Results

- **100 mg QD lorundrostat: SBP reduction 11.4 mmHg (SD 2.5) — similar magnitude to Cohort 1**
- This proved the drug works even without the suppressed-renin/elevated-aldosterone phenotype, eliminating the need for ARR-based patient selection in subsequent trials.

#### Safety

- **6 patients (3%) had K+ \>6.0 mmol/L** — corrected with dose reduction or discontinuation
- **No cortisol insufficiency** events
- No serious treatment-related deaths

Clinical Pearl — The Two-Cohort Design Was Smart

Most novel HTN drugs design enrichment trials around a phenotype (aldosterone, renin, salt-sensitive, etc) to maximize signal. Target-HTN did this in Cohort 1, then proved the drug also works in Cohort 2 without enrichment — meaning real-world prescribing does not require expensive ARR testing. **This is one reason lorundrostat may have a smoother regulatory path than osilodrostat ever did.**

### 2.2 Advance-HTN — Phase 2 with 24-h ABPM Primary Endpoint (Laffin et al., NEJM 2025, PMID 40267417)

| Element | Detail |
|----|----|
| Design | Phase 2 RCT, double-blind, placebo-controlled |
| Run-in | 3 weeks of standardized antihypertensive regimen + 24-h ABPM gate |
| Inclusion gate | 24-h ambulatory BP ≥130/80 after standardized regimen |
| Randomization | 1:1:1 |
| Arms | Placebo (n=95); 50 mg stable (n=94); 50 mg → 100 mg dose-adjustment (n=96) |
| Primary endpoint | Change in 24-h ABPM SBP at week 12 |
| Population | Mean age 60 years, **53% Black**, 285 total |
| ClinicalTrials.gov | NCT05769608 |

#### Primary Endpoint Results — 24-h ABPM SBP Change at Week 12

| Group | LS Mean Change (mmHg) | Δ vs Placebo | 97.5% CI |
|----|----|----|----|
| Placebo | **−7.4** | reference | — |
| Stable 50 mg | **−15.4** | **−7.9** | −13.3 to −2.6 |
| Dose-adjustment (50→100 mg) | **−13.9** | **−6.5** | −11.8 to −1.2 |

**Key finding:** Stable 50 mg outperformed dose-adjustment up to 100 mg. **The higher dose did not give better BP lowering — same flat dose-response curve seen in Target-HTN and BrigHTN.** This is becoming a class-defining feature of the ASi: 50 mg lorundrostat and 2 mg baxdrostat are at the top of the dose-response curve for BP, with higher doses adding side effects without adding efficacy.

#### Safety in Advance-HTN

- K+ \>6.0 mmol/L: **5% stable, 7% dose-adjusted, 0% placebo**
- Run-in design excluded patients with eGFR-related risk factors before randomization
- Placebo SBP reduction of 7.4 mmHg in the run-in confirms the pseudoresistance lesson from PRECISION applies here too

### 2.3 Launch-HTN — Phase 3 Pivotal (Saxena et al., JAMA 2025, PMID 40587141)

| Element | Detail |
|----|----|
| Design | Phase 3, multicenter, RCT, double-blind |
| Sites | 159 across 13 countries |
| Enrollment | November 2023 – September 2024 |
| N randomized | 1083 |
| Randomization | 1:2:1 — escalation 50→100 mg (n=270) : stable 50 mg (n=541) : placebo (n=272) |
| Background | 2-5 antihypertensive medications |
| Primary endpoint | Change in automated office SBP at week 6 (50 mg pooled vs placebo) |
| Inclusion gates | SBP ≥130, K ≤4.8, Na ≥135, eGFR \>45, \<25% eGFR drop |
| Population | Mean age 61.6, 46.9% female, 28.7% Black, 63.3% obese |
| ClinicalTrials.gov | NCT06153693 |

#### Primary Endpoint — Office SBP at Week 6

| Group | LS Mean Change (mmHg) | Δ vs Placebo | 95% CI | P value |
|----|----|----|----|----|
| Pooled 50 mg lorundrostat (n=808) | **−16.9** | **−9.1** | −13.3 to −4.9 | **\<0.001** |
| Placebo (n=272) | **−7.9** | reference | — | — |

**This is the cleanest, largest evidence for lorundrostat’s BP lowering effect.** The placebo-corrected SBP reduction of −9.1 mmHg in a Phase 3 setting with rigorous run-in is essentially identical to baxdrostat’s BaxHTN result (approximately −9 mmHg).

#### Safety

- Treatment discontinuation due to hyperkalemia: **2/541 (0.37%)** in stable 50 mg, **1/270 (0.37%)** in dose-adjustment
- Treatment discontinuation due to hyponatremia: 2/541 (0.37%) and 1/270 (0.37%)
- Treatment discontinuation due to eGFR reduction: 3/541 (0.56%) and 0/270
- Treatment-emergent adverse events overall: 49.9% (538/1078) — mostly mild-to-moderate

What Launch-HTN Did NOT Test

Launch-HTN required **eGFR \>45** at entry, K+ ≤4.8, and Na ≥135. **It excluded the patients most likely to develop hyperkalemia.** The 0.37% hyperkalemia discontinuation rate is for a population pre-selected away from K+ risk. In CKD stages 3b-4, where Andy practices most, the rate will be higher. The BAX-CKD experience with baxdrostat (41% K+ signal) should be the cautionary template — lorundrostat just has not been stressed in that population yet.

### 2.4 Trial Comparison Table

| Dimension | Target-HTN | Advance-HTN | Launch-HTN |
|----|----|----|----|
| Phase | 2 dose-ranging | 2 confirmatory | 3 pivotal |
| N | 200 | 285 | 1083 |
| Design | Dose-ranging RCT | RCT, ABPM primary | RCT, office SBP primary |
| Run-in | 4 weeks | 3 weeks standardized regimen | Standardized regimen |
| Background | 2+ HTN drugs | 2-5 HTN drugs | 2-5 HTN drugs |
| Primary endpoint | Office SBP wk 8 | 24-h ABPM SBP wk 12 | Office SBP wk 6 |
| Best dose | 50 mg QD | 50 mg stable | 50 mg pooled |
| Δ SBP vs placebo | −9.6 mmHg | −7.9 mmHg (24-h ABPM) | −9.1 mmHg (office) |
| K \>6.0 % | 3% | 5-7% | low (excluded gate) |
| Year | 2023 | 2025 | 2025 |
| Journal | JAMA | NEJM | JAMA |
| First author | Laffin | Laffin | Saxena |
| PMID | 37690061 | 40267417 | 40587141 |

The **three-trial signal** is impressive. Four randomized comparisons (counting two cohorts of Target-HTN), three different primary endpoints (office BP, ABPM, Phase 3 office BP), all showing approximately 7-10 mmHg placebo-corrected SBP reduction. **The lorundrostat program is more methodologically diverse than the baxdrostat program** (which has BrigHTN, HALO failed, BaxHTN, BAX-CKD).

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## 3. Lorundrostat vs Baxdrostat — Head-to-Head Comparison

This is the question Andy will get asked at the AZ dinner: **why baxdrostat over lorundrostat (or vice versa)?** The honest answer:

| Dimension | Lorundrostat | Baxdrostat | Edge |
|----|----|----|----|
| CYP11B2/CYP11B1 selectivity | approximately 374:1 | approximately 100:1 | Lorundrostat (in vitro) |
| Pivotal Phase 3 | Launch-HTN n=1083 | BaxHTN n=794 | Lorundrostat (larger N) |
| ABPM Phase 2 | Advance-HTN −7.9 mmHg 24-h | None reported | Lorundrostat |
| Office SBP placebo-corrected | approximately −9.1 mmHg | approximately −9 mmHg | Tie |
| CKD-specific Phase 2 | None | BAX-CKD n=195 | Baxdrostat (more data, even if signal is concerning) |
| Hyperkalemia rate (general HTN) | 5-7% K\>6.0 | similar | Tie |
| Hyperkalemia rate (CKD) | Unknown | 41% any TEAE in BAX-CKD | Lorundrostat (favorable in absence of data) |
| HF trial | None | None | Tie |
| DKD trial | None | None | Tie |
| FDA approval (October 3, 2026) | Pending | Approved May 2026 | Different regulatory status |
| Developer | Mineralys (small biotech) | AstraZeneca (large pharma) | Baxdrostat (commercial muscle, marketing reach) |
| Once-daily dosing | Yes (50 mg) | Yes (1-2 mg) | Tie |
| Drug interactions | Hepatic CYP metabolism | Limited interactions | Baxdrostat (cleaner profile so far) |
| Cost projection | TBD | TBD | TBD |

The Honest Differentiator

Lorundrostat has a **better selectivity ratio on paper, more Phase 2/3 evidence, and a 24-h ABPM Phase 2 that baxdrostat lacks**. Baxdrostat has **AstraZeneca’s commercial reach, the BAX-CKD CKD-specific data (despite the worrying signal), and a cleaner drug interaction profile**. From a **clinical evidence standpoint**, lorundrostat is currently the more complete package. From a **commercial-positioning standpoint**, baxdrostat will likely be more visible in clinic because of AZ’s sales infrastructure. **Neither has hard outcome data, neither has HF data, neither has DKD trials. Both are 4th-line options for true resistant HTN where MRA is contraindicated or inadequate.**

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## 4. The CKD Question — Lorundrostat’s Big Unknown

**This is the section that matters most for nephrology.**

### 4.1 What We Don’t Know

Lorundrostat has **no published CKD-specific Phase 2 trial**. Launch-HTN excluded eGFR \<45. Target-HTN and Advance-HTN did not stratify or report CKD subgroups in their primary publications. This leaves nephrologists in an uncomfortable position: the drug class clearly works on BP, the mechanism predicts CKD benefit (lower aldosterone → less proteinuria, less fibrosis), but **the safety database in advanced CKD does not yet exist for lorundrostat**.

### 4.2 What BAX-CKD Tells Us About the Class Risk

Baxdrostat’s BAX-CKD trial showed a **41% hyperkalemia signal** in patients with CKD on baxdrostat vs 5% on placebo. This is the cautionary template. Whether lorundrostat’s better in vitro selectivity ratio translates to a smaller CKD hyperkalemia rate is unknown. **The mechanistic case is the same:** lower aldosterone → less K+ excretion in the cortical collecting duct → hyperkalemia, especially when GFR is already low and tubular K+ secretion is borderline.

### 4.3 What I’d Want Before Prescribing in CKD 3b-4

1.  A dedicated lorundrostat-CKD Phase 2 trial with eGFR 25-45 and granular K+ monitoring
2.  Direct comparison vs BAX-CKD population characteristics
3.  Hard outcome data on UACR slope and eGFR slope (analogous to FIDELIO-DKD for finerenone)
4.  Combination data with SGLT2i (the natriuretic offset for hyperkalemia and fluid retention)

**Until those exist, lorundrostat in CKD is empirical extrapolation. So is baxdrostat. So is the entire ASi class for nephrology indications.**

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## 5. Practical Prescribing — When and How

### 5.1 Patient Selection (Best Candidate)

- True resistant HTN confirmed by ABPM
- Already on optimized triple therapy
- Adherence verified
- Pseudoresistance excluded
- Spironolactone failed, contraindicated, or caused gynecomastia
- eGFR \>45 (until CKD-specific data available)
- K+ ≤4.8 at baseline
- No HFrEF history
- No active liver disease

### 5.2 Dosing

| Step | Dose | Notes |
|----|----|----|
| Start | **50 mg PO daily** | Same dose used in Launch-HTN pivotal |
| Titration | Consider 100 mg if SBP not at goal AND K+ \<4.5 | Limited additional benefit, more K+ risk |
| Renal | Avoid eGFR \<45 until more data | Trials excluded this population |
| Hepatic | Caution; CYP-mediated metabolism | Limited data |

### 5.3 Monitoring

| Parameter | Baseline | Frequency |
|----|----|----|
| BMP / K+ / Na+ / Cr / eGFR | Yes | 2 weeks, 4 weeks, 8 weeks, then quarterly |
| BP (preferably home or ABPM) | Yes | 2 weeks, 6 weeks, then quarterly |
| Adrenal axis (cortisol, ACTH) | Not routinely | Only if symptoms |
| Pregnancy test | If applicable | Investigational protocol; no approved US label as of October 3, 2026 |

### 5.4 Hyperkalemia Management Algorithm

1.  **K+ 5.0-5.4:** Continue, recheck in 1-2 weeks. Dietary K+ counseling. Consider stopping K+ supplements.
2.  **K+ 5.5-5.9:** Hold lorundrostat. Stop ACEi/ARB temporarily if dual therapy. Diet review. Recheck in 1 week.
3.  **K+ ≥6.0:** Discontinue lorundrostat. Treat hyperkalemia (calcium gluconate IV, insulin/dextrose, kayexalate or patiromer). Do not rechallenge unless K+ stably \<5.0 with clear trigger identified.

Clinical Pearl — The K+ Buffer Drugs

Patiromer (Veltassa) and sodium zirconium cyclosilicate (Lokelma) were essentially developed to enable RAAS therapy in CKD. They work just as well to enable ASi therapy. **Combination ASi + K+ binder is the future of resistant HTN management in CKD** — but no head-to-head trial has tested this strategy yet.

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## 6. Open Questions and Honest Gaps

1.  **No dedicated CKD trial.** The most important nephrology question is unanswered.
2.  **No hard outcome data.** Same gap as baxdrostat. PROBE-style trials are not yet planned.
3.  **No HF trial.** EF preserved or reduced — neither has a lorundrostat outcome trial.
4.  **No DKD outcome trial.** FIDELIO-DKD-style proteinuria/eGFR slope endpoints are absent.
5.  **No SGLT2i combination data.** The obvious complementary drug pairing has not been tested.
6.  **No head-to-head with baxdrostat.** We compare across trials with different populations and endpoints.
7.  **No long-term safety beyond 12 weeks for most patients.** Launch-HTN’s primary endpoint was week 6.
8.  **The 374:1 selectivity ratio is in vitro.** In vivo cortisol axis impact has been measured (preserved ACTH and cortisol in the trials) but the mechanistic advantage over baxdrostat is theoretical until proven by a head-to-head.

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## 7. Vault Cross-References

- baxdrostat aldosterone synthase inhibitor medical review — companion ASi review (BrigHTN, BaxHTN, BAX-CKD, HALO)
- aprocitentan dual endothelin antagonist resistant hypertension medical review — alternative add-on for true RH
- renal denervation resistant hypertension medical review — procedural alternative
- 2025 AHA expanded htn guideline analysis — current guideline framework
- Hypertension Hub
- hypertension management report
- MRA vs nsMRA vs aldo synthase inhib — class comparison file in Cardiology folder

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## References

1.  **Laffin LJ, Rodman D, Luther JM, et al.** Aldosterone Synthase Inhibition With Lorundrostat for Uncontrolled Hypertension: The Target-HTN Randomized Clinical Trial. **JAMA** 2023;330(12):1140-1150. PMID: [37690061](https://pubmed.ncbi.nlm.nih.gov/37690061/). [DOI](https://doi.org/10.1001/jama.2023.16029)

2.  **Laffin LJ, Kopjar B, Melgaard C, et al.** Lorundrostat Efficacy and Safety in Patients with Uncontrolled Hypertension. **N Engl J Med** 2025;392(18):1813-1823. PMID: [40267417](https://pubmed.ncbi.nlm.nih.gov/40267417/). [DOI](https://doi.org/10.1056/NEJMoa2501440)

3.  **Saxena M, Laffin L, Borghi C, et al.** Lorundrostat in Participants With Uncontrolled Hypertension and Treatment-Resistant Hypertension: The Launch-HTN Randomized Clinical Trial. **JAMA** 2025;334(5):409-418. PMID: [40587141](https://pubmed.ncbi.nlm.nih.gov/40587141/). [DOI](https://doi.org/10.1001/jama.2025.9413)

4.  **Saxena M, Rodman D.** Lorundrostat for Uncontrolled Hypertension and Treatment-Resistant Hypertension—Reply. **JAMA** 2025;334(20):1856-1857. PMID: [41123913](https://pubmed.ncbi.nlm.nih.gov/41123913/). [DOI](https://doi.org/10.1001/jama.2025.16170)

5.  **Feldman JM, Frishman WH, Aronow WS.** Emerging Therapies for Treatment-Resistant Hypertension: A Review of Lorundrostat and Related Selective Aldosterone Synthase Inhibitors. **Cardiol Rev** 2026;34(2):113-116. PMID: [38358268](https://pubmed.ncbi.nlm.nih.gov/38358268/). [DOI](https://doi.org/10.1097/CRD.0000000000000665)

6.  **Irfan H, Ahmed A, Nawani KD.** Hypertension and Lorundrostat: Key Discoveries From the TARGET-HTN Trial. **Curr Probl Cardiol** 2024;49(1 Pt C):102144. PMID: [37858848](https://pubmed.ncbi.nlm.nih.gov/37858848/). [DOI](https://doi.org/10.1016/j.cpcardiol.2023.102144)

7.  **Smeijer JD, Kohan DE, Dhaun N, et al.** Endothelin receptor antagonists in chronic kidney disease. **Nat Rev Nephrol** 2025;21(3):175-188. PMID: [39643698](https://pubmed.ncbi.nlm.nih.gov/39643698/). [DOI](https://doi.org/10.1038/s41581-024-00908-z)

8.  **Georgianos PI, Agarwal R.** Hypertension in chronic kidney disease-treatment standard 2023. **Nephrol Dial Transplant** 2023;38(12):2694-2703. PMID: [37355779](https://pubmed.ncbi.nlm.nih.gov/37355779/). [DOI](https://doi.org/10.1093/ndt/gfad118)

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**Andrew Bland, MD, FACP, FAAP** Medical Associates Dept of Nephrology \| University of Illinois College of Medicine at Peoria \| University of Dubuque PA Program \| Butler College of Osteopathic Medicine


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