Matt Luther, MD MSCI

Treatment of hypertension - Lasker Foundation Explore All 1957 Winners & Awards > Rustom Jal VakilKing Edward VII Memorial Hospital, Bombay For studies on the use of reserpine in the treatment of hypertension. The story of Rauwolfia…

#LaskerLaureate Rustom Jal Vakil was born #OTD in 1911. He won a #LaskerAward in 1957 for his studies on the use of reserpine in the treatment of #hypertension. ow.ly/bFTR50FunRI 🧪

almost always lower dose 12.5-25, occasionally higher 50-100mg.
hyperkalemia/CKD > gynecomastia > dysmenorrhea of course can be limiting

Yes you should be able to reduce medications after adding Spironolactone.
I withdraw based on other adverse med effects (edema = CCB; K = thiazide/RAASi)

I use this figure in my talks on Resistant HTN...(observational, but holds up imo)

pubmed.ncbi.nlm.nih.gov/11991219/

Primary Aldosteronism: An Endocrine Society Clinical Practice Guideline AbstractBackground. Primary aldosteronism (PA), a primary adrenal disorder leading to excessive aldosterone production by one or both adrenal glands, is a

New PA Endo guideline is also out by experts @anandvaidya17.bsky.social #Cardiosky @hswapnil.medsky.social doi.org/10.1210/clin...

Urinary Albumin-to-Creatinine Ratio, Serum Potassium Level, Estimated Glomerular Filtration Rate, and Systolic Blood Pressure over Time.

The first #ERA25 simultaneous pub

CONFIDENCE trial of empagliflozin + finerenone in N = 579

Greater reduction in ACR and BP
Note the impressive GFR dip

www.nejm.org/doi/full/10....

Bring back methyldopa too!

Standardized treatment in advance-HTN included thiazide + ARB for all.

Upcoming Launch-HTN uses standard background meds so will be a mix of real world regimens.
Longer term open label followup is ongoing too.

I'm gonna guess Geriatrics

old drugs in HT

Plenary at @hypertensioncanada.bsky.social with @drjmluther.bsky.social on new drugs

He starts of with the really old drugs!

#CHC25

*in rodents

Add-On Treatment With Zilebesiran for Inadequately Controlled Hypertension This randomized clinical trial examines the efficacy and safety of zilebesiran vs placebo when added to a standard antihypertensive medication in adult patients with uncontrolled hypertension.

Phase 2 trial of the new antihypertensive agent, ultra-long-acting (q6 month), subq, small interfering RNA against angiotensinogen (Zilebesiran), hit JAMA!

h/t @drjmluther.bsky.social

jamanetwork.com/journals/jam...

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Hyponatremia define here as <135, and also while all patients on a thiazide. Suspect clinically significant hypoNa is much less common.
#NephJC

I do not have any inside info- doesn't look like it is being studied in the US, likely due to lack of patent protection. But it appears much less selective than newer agents. It is just R-fadrazole.

the bigger issue is - don't block cortisol synthesis, which ramps up ACTH and revs up the steroid pathway and further augments DOC accumulation.
#NephJC

btw @kidneyboy.bsky.social this pathway needs to be taught to our Neph fellows so they can think this problem out like you're doing

Indapamide 2.5mg or if previously on HCTZ continue that dose (if I recall correctly).
Plus Olmesartan 40mg in all.
If previously on 3 drugs then Amlodipine 10mg or max tolerated dose used.
#NephJC

absolutely.

Not sure the numbers are sig different, but I think your rationale is correct. The dose would have been pushed up to 100mg only in the most resistant #NephJC

Theoretically:
- it targets the primary issue in many patients- unregulated aldosterone production.
-avoid effect of further elevated Aldo during MRA treatment

Obvs -avoid gynecomastia and off-target effects of Spiro.
For other MRAs it has always been difficult to push dose high enough.
#NephJC

I would classify Osilodrostat as a nonselective inhibitor. It impaired Cort-stim response in those doses. also Lowered BP - would not include with selective ASIs.

Osilodrostat is now approved for treatment of Cushing's (Cortisol inhibition) at much higher dose than used in these trials.
#NephJC

That is why they added the Cystatin-C measurement to help clarify.
I do expect some hemodynamic effect with treatment of uncontrolled HTN into a lower range, though.
#NephJC

correct. Aldo usually increases with MRA treatment.
Renin increases during both ASI and MRA.

Plasma Aldo provides a snapshot in time.
24hr urine Aldo may give a better measure of coverage.
#NephJC

At very high dose, ASIs increase DOC.
Less potent MR agonist - BP reduction and Renin increase is still evident.
CYP11B1 inhibition also increases ACTH, DOC.
Lower dose for each ASI is chosen in part to limit DOC response.
#NephJC

Baxdrostat HALO study failed to reach primary endpoint - I don't know why but VERY large placebo drop in AOBP.
Trial design or conduct error. I don't think it was the drug.
#NephJC

Still early, safety first.
Hyponatremia defined as <135 was very annoying to me since most of my patients live at 130-135 on a thiazide.
#nephJC

As data emerges, the 3 new agents are much more selective than prior drugs. Still need more data on Vicadrostat (done but not shown in publications).
#nephJC

It has been the main barrier to development- off target Cortisol inhibition, due to the high homology and overlapping functionality.
#nephJC

Matt Luther, Nephrologist/HTN specialist
COI: Mineralys consulting
#NephJC

Mineralys Therapeutics Announces Late-Breaking Presentation of Data from the Launch-HTN Pivotal Trial of Lorundrostat in Uncontrolled or Resistant Hypertension at 34th European Meeting on Hypertension and Cardiovascular Protection (ESH 2025)

Today we presented detailed results from our pivotal Ph3 Launch-HTN trial at #ESH2025, reinforcing the promise of lorundrostat as a new treatment approach for aldosterone driven #hypertension.

Read our press release to learn more: ir.mineralystx.com/news-events/...

$MLYS #bloodpressure

Figure of survival curve showing no difference

There you have it: BEDMED published in @jama.com

jamanetwork.com/journals/jam...

h/t @drjmluther.bsky.social

No difference in bedtime versus morning BP meds - as expected

#NephSky #Hypertension
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Lorundrostat Efficacy and Safety in Patients with Uncontrolled Hypertension | NEJM Aldosterone dysregulation contributes to hypertension. Lorundrostat is an aldosterone synthase inhibitor, but data on its efficacy and safety in patients with hypertension are limited. In this mult...

Aaand it’s official, we have a new antihypertensive class!!!! 🎉🍾🎊

I like this RCT design in particular because it was open to both uncontrolled not-yet-resistant AND resistant hypertensive patients, opening to door to prescribe it as an earlier line agent

www.nejm.org/doi/full/10....