Is Baxdrostat the Missing Link in Hypertension Treatment? With Payal Kohli, MD

Hypertension affects an estimated 1.4 billion people worldwide, yet approximately 50% of patients in the US who are already taking multiple antihypertensive medications continue to have persistently elevated blood pressure. For the roughly 23 million US patients who remain uncontrolled on ≥ 2 medications, the field has seen little meaningful therapeutic innovation in more than 2 decades.

On May 18, 2026, the FDA approved baxdrostat (Baxfendy, AstraZeneca) as the first-in-class aldosterone synthase inhibitor (ASI) for the treatment of hypertension in adults whose blood pressure is not adequately controlled on existing antihypertensive therapy. The approval was based on results from the BaxHTN phase 3 trial in which baxdrostat 2mg reduced mean seated systolic blood pressure by 15.7 mmHg from baseline at 12 weeks, a placebo-adjusted reduction of 9.8 mmHg (95% CI, -12.6 to -7.0; P <.001), on top of standard-of-care antihypertensive regimens. The 1mg dose produced a placebo-adjusted reduction of 8.7 mmHg (95% CI, -11.5 to -5.8; P <.001).

Results were consistent across both uncontrolled and treatment-resistant subgroups, and the drug was generally well tolerated. Separate data from the Bax24 phase 3 trial confirmed statistically significant reductions in 24-hour ambulatory systolic blood pressure in patients with resistant hypertension.

Unlike mineralocorticoid receptor antagonists, which block the downstream effects of aldosterone after it is produced, baxdrostat targets aldosterone synthase (CYP11B2) upstream, directly inhibiting aldosterone synthesis with high selectivity over cortisol-producing pathways.

Payal Kohli, MD, a general and preventive cardiologist at Cherry Creek Heart and an associate adjunct professor of cardiology at Duke University and Johns Hopkins University, sat down with Patient Care Online to discuss how baxdrostat's mechanism fits into the current treatment landscape and which patients are most appropriate candidates for the new therapy:

Patient Care Online: Baxdrostat works differently from the hypertension medications clinicians are used to prescribing for a primary care audience. How would you explain what makes this drug's mechanism unique?

Kohli: As a cardiologist, I'm very excited to finally have a drug in my armamentarium that works by a parallel mechanism of action. As primary care doctors, we're very used to using thiazide diuretics, we're used to using ACEs and ARBs, we're used to using calcium channel blockers, those are sort of our 3 first line medications. Believe it or not, thiazide diuretics and mineralocorticoid receptor antagonists can actually raise the aldosterone level, and what we've realized is that letting the aldosterone be manufactured or produced and then trying to antagonize it with an MRA is sort of backwards logic.

What this drug does is it goes upstream, so it targets what's called aldosterone synthase. It's the first treatment in this class of medications called aldosterone synthase inhibitors, and it is very specific for aldo synthase. It has a 1 to 100 specificity for aldosterone synthase compared to cortico synthase, so we're not so worried about affecting cortisol production when we reduce aldosterone synthesis, but it goes upstream.

I like to use the analogy of think about having a clogged bathtub and you've got the faucet on all the way and you're bailing the water out. That's really what an MRA is doing, and the MRAs can actually increase that aldosterone level even more because of that homeostatic feedback loop. Here, what you're doing is you're turning down the faucet, and so you're not inhibiting it 100%, but you're largely inhibiting aldosterone synthase, which means that you're decreasing the production of aldosterone, and therefore the faucet is turned down. You don't have to bail out that water quite as quickly. So, it’s a novel mechanism of action, and I'm very excited to use it in my patients who have uncontrolled hypertension.

The appropriate patient phenotype for who would get this is somebody who is on 2 or more blood pressure medications, and they're not at their goal. That's where we think aldosterone may be the missing link in really helping to bridge that treatment gap.

Patient Care Online: In the Bax Hypertension trial, baxtrostat lowered seated systolic blood pressure by nearly 9 to 10 millimeters per mercury, more than placebo at 12 weeks. How meaningful is that level of reduction for patients who are already on multiple blood pressure medications?

Kohli: It is incredibly meaningful, and I like to joke around that this may be the GOAT of blood pressure medications, the greatest of all time, because we really don't have a lot of medicines that lead to a nearly 10 point systolic reduction in blood pressure. Now I want to remind our audience that, of course, every 10 point systolic blood pressure that I reduce, I reduce your risk of major adverse cardiovascular events, such as MI and stroke, by 20%. Even though Bax Hypertension is not an outcomes trial, the primary endpoint was reduction in seated blood pressure, but it's a really impressive reduction, and it can help again to bridge that gap in our patients, especially in the context of the new ACC AHA guidelines, where we're now shooting for even more stringent blood pressure targets.

These guidelines have now made 120 the new 130 and we're saying for most patients, if you can, try to get them below a systolic blood pressure of 120. I think it's a really efficacious medication, and keep in mind that the Bax hypertension trial was done on the background of several other medicines, so patients in this trial by protocol design were on multiple other blood pressure medicines, so you're really talking about an additional systolic reduction of nearly 10 points on top of what they were already taking.

Patient Care Online: The approval is for adults whose blood pressure is still not adequately controlled, despite other anti-hypertensive medications like you alluded to before. In your view, which patients in everyday practice are most likely to benefit from baxdrostat?

Kohli: I can think of so many patients, because I feel like nearly half of my patients with hypertension are uncontrolled, and that is a staggering statistic. We're not bad people, but we do bad medicine, and part of that challenge is really that we've not had a lot of innovation in the field of hypertension. I mean, we're using thiazides, which are 68 years old. They're decades old medications, and again, like I said, thiazides can raise your aldosterone levels, as can MRAs, and so a lot of these medicines kind of work against themselves.

We also, of course, know that some patients with MRAs have significant sexual or hormonal side effects, because that medication has a non-specificity and hits multiple different receptors that can cause many of those sexual side effects. So for me, this is a really important advance in the field of hypertension, to have something that has a novel mechanism of action like this that is so efficacious and that is so well tolerated. It's not like we're seeing a lot of side effects or concerning signals either, because tolerability is a really important part of patient compliance, especially when blood pressure can be asymptomatic, high blood pressure can be asymptomatic, but the treatments for high blood pressure can be symptomatic, right? We can cause symptoms with the treatments, and that can affect patient compliance as well.

Patient Care Online: Going back to the trial, it showed strong blood pressure reductions, but clinicians will also be thinking about monitoring, especially for potassium, sodium, and kidney function. What should primary care physicians keep in mind before and after starting this medication with their patients?

Kohli: In the clinical trials, we saw signals for hyperkalemia, which makes sense because you're reducing aldosterone production, which can affect your potassium homeostasis. So, usually 2 to 4 weeks after, you should check serum potassium, and certainly those patients that have chronic kidney disease or the patients that have more elevated potassiums at baseline are at higher risk for hyperkalemia. Keep in mind that everybody in the Bax Hypertension trial had a GFR greater than 45, so you really want to live in that zone when you're thinking about which of your patients are most appropriate to start this, and you want to check their GFR before you initiate it.

Then you want to check a basic metabolic panel after to keep an eye not just on that potassium, but also the sodium. We know that hyponatremia can occur from many different drugs, and so it's important to monitor that as well. Thankfully, the risk of hyponatremia or hyperkalemia was pretty rare and infrequent in the trial, so it occurred at very low rates, and the drug itself was well tolerated in terms of patient-reported outcomes. Patients complained of dizziness, and they complained of muscle spasms, and then a small subset of patients had hypotension, because it lowers their blood pressure, lowered it a bit too much, but it's really not that challenging a drug to use, because you just have to check a CMP essentially a few weeks after you start it, anytime you titrate the dose, and of course, if you're changing any other medicines that affect potassium homeostasis, like an ACE or an ARB or a thiazide diuretic, then of course you would want to recheck that CMP again.

Patient Care Online: Where do you see baxdrostat fitting into the hypertension treatment pathway? Is this something you see being used mainly after other options have failed, or could it be used earlier for patients?

Kohli: It’s such an important question. I think, looking into the future, I might be using it earlier, but today, based on the FDA approval, I'm certainly not using it as a first line agent. I'm still reaching for my old friends, my thiazides, my ACEs, my ARBs, my calcium channel blockers, and when that cocktail of medications is either not tolerated or it's not resulting in getting them to their goal, which, like I said, now the goals are even more stringent at less than 120, then I think I'm going to use this medication.

Keep in mind you can't use this medication in combination with an MRA, so instead of reaching for that MRA, I would reach for this particular medication, because again, we're going upstream, we're targeting aldo production rather than allowing the aldosterone to be made and then trying to antagonize the receptor.

Patient Care Online: Is there anything else you would like to add or highlight?

Kohli: Just a couple more points to keep in mind. Certainly, we talk about not just a snapshot of blood pressure control, but ambulatory blood pressure control, that's long lasting and 24 hours, so the Bax24 trial looked at long term blood pressure control over the entire 24 hour period, and the nice thing about this drug is that it's got a 29 hour half life, so we really do see kind of prolonged extended blood pressure control. We're not seeing a lot of the ups and the downs, and we know that early morning blood pressure control is really important when it comes to prognosis for cardiovascular risk outcomes, so that was really reassuring to see in the trial as well.

Editors’ note: Kohli reports relevant disclosures with Lexicon Pharmaceuticals, Novartis, Amgen, AstraZeneca, Boston Scientific, Bristol-Myers Squibb Company, Merck, and others.

References

1. Jennings S. FDA Approves Baxdrostat for Uncontrolled Hypertension on Background Therapy. Patient Care. May 18, 2026. Accessed May 27, 2026. https://www.patientcareonline.com/view/fda-approves-baxdrostat-for-uncontrolled-hypertension-on-background-therapy

2. CDC. High Blood Pressure Facts. January 28, 2025. Accessed May 27, 2026. https://www.cdc.gov/high-blood-pressure/data-research/facts-stats/index.html