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Enhancing Resistant Hypertension Care: Appropriate Screening and Treatment for Aldosterone-Related Considerations

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Released: August 24, 2026

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Examine evidence-based and guideline-directed approaches to diagnosing resistant hypertension, such as using appropriate blood pressure measurement techniques, ruling out pseudoresistance, and screening for aldosterone-driven disease. Then enhance your understanding of the latest advancements in managing resistant hypertension with mineralocorticoid receptor antagonists and aldosterone synthase inhibitors.

Debbie Cohen
Debbie Cohen, MD
Resistant hypertension screening and management

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Key Takeaways
  • All patients with resistant hypertension or hypokalemia in the setting of hypertension, among others, should be screened for primary aldosteronism.
  • MRAs are the guideline-directed fourth-line therapy for patients with resistant hypertension and can be safely used in this setting.
  • Aldosterone synthase inhibitors are an emerging class of add-on therapies showing promise in providing cardiovascular benefit to patients with resistant hypertension, yet further data are needed to understand their role in the larger cardiovascular treatment algorithm.

Distinguishing between true resistant hypertension and pseudoresistance requires a detailed workup that includes measuring blood pressure correctly with the right cuff size and good technique. If healthcare professionals (HCPs) suspect that white coat effect is present, patients’ ambulatory or out-of-office blood pressure should be monitored. In cases of pseudoresistance, usually poor measurement techniques are at fault, or there are other factors, such as over-the-counter medications like nonsteroidal anti-inflammatory drugs and decongestants, interfering with patients’ blood pressure. Adherence issues are also a major contributor to apparent or pseudoresistant hypertension, and partial or total nonadherence can be present in over 50% of patients with treatment-resistant hypertension.

Aldosterone in Resistant Hypertension
There is now a greater understanding of the larger role aldosterone plays in resistant hypertension, not just with the renin–angiotensin–aldosterone pathway but also with the sympathetic pathway. For example, studies like PATHWAY-2 have demonstrated that even patients with higher plasma renin levels responded well to mineralocorticoid receptor agonists (MRA) like spironolactone.

Because of these studies, there also is a consensus among HCPs that many patients with resistant hypertension have relative hyperaldosteronism that drives their uncontrolled blood pressure. In the more extreme form, less than a third of patients with resistant hypertension have primary aldosteronism (PA); however, many more cases are primarily driven by aldosterone dysregulation without a PA diagnosis. That is why patients may respond well to very low doses of MRAs.

Diagnosing Aldosterone-Driven Disease
There are some guidelines for evaluating for aldosterone-driven resistant hypertension.  I think that anyone who meets the diagnostic criteria for resistant hypertension—persistent, uncontrolled blood pressure despite using 3 optimized antihypertensive therapies, including a diuretic, or controlled blood pressure that requires 4 or more antihypertensive therapies—should have their plasma renin activity and aldosterone levels checked.

In my clinic, we have done this for around 20 years, and about a third of our patients who are considered resistant receive a confirmed PA diagnosis. HCPs should understand that PA is much more common in the resistant hypertension population and widely undertested, misdiagnosed, or entirely missed in clinical practice. Current research demonstrates that less than 2% of patients are screened for PA despite meeting criteria.

The guideline-directed indications that signal patients should be screened for PA include those with:

  • Resistant hypertension regardless of potassium levels
  • Hypokalemia in the setting of hypertension
  • Comorbid obstructive sleep apnea and hypertension
  • An adrenal mass
  • Family history of primary aldosteronism
  • Prior or family history of stroke at a young age

The more people we screen, the more awareness there will be, resulting in an increased diagnosis of PA or relative hyperaldosteronism. But there is a lot of work that still needs to be done. First is HCP and patient education. PA is a recognized endocrine disease that is more common than people originally thought, so educating HCPs and patients about it and asking HCPs to screen earlier is critical.Second, many HCPs do not know what to do with patients’ renin/aldosterone screening results. They may feel overwhelmed or not know how to deal with it appropriately. That is why there is a large push from national internal medicine, nephrology, and endocrine societies to screen and act early. Obviously, newer therapies are coming out as well, which has helped raise awareness about PA. Yet there remains a lack of awareness, inability to interpret results, and knowledge on how to act on results among some HCPs.

Current Treatment Strategies for Resistant Hypertension
The guidelines generally recommend adding an MRA as the fourth-line therapy. For HCPs who are in the know, we prescribe these agents a lot. Unfortunately, in the primary care setting where more than 90% of patients with hypertension are seen, the uptake of these agents is much lower. Primary care HCPs and patients often are concerned about using MRAs due to their associated adverse events. For example, some might not tolerate these therapies well, and others may be scared about potential potassium issues, especially if they have underlying chronic kidney disease. Most HCPs do not want to risk patients developing hyperkalemia or, less commonly, hyponatremia, nor do they want to create more work for themselves, as this does require monitoring with laboratory measurements. Therefore, HCPs must address this reluctance, either within themselves or among patients, to refrain from underusing MRAs as indicated.

Enter Aldosterone Synthase Inhibitors
A novel class of agents being studied in resistant hypertension comprises aldosterone synthase inhibitors (ASIs), with baxdrostat as the only one currently approved by the FDA. It is indicated to treat hypertension in combination with other antihypertensive therapies in adults with inadequately controlled blood pressure. I have some patients on baxdrostat, and they seem to be doing well. 

There are also several cardiovascular outcomes trials looking at ASIs in combination with SGLT2 inhibitors. Once we get the results, we should have a solid placement of where ASIs fit in the larger cardiovascular treatment algorithm. In addition, these trials will hopefully make a stronger case for health insurance coverage and for HCPs to feel confident about prescribing ASIs when the time comes.

Other investigational ASIs (eg, lorundrostat, vicadrostat) are being evaluated in trials, and hopefully their results will confirm both blood pressure and cardiovascular benefits.

Regarding PA, there is 1 ongoing phase III study for baxdrostat. If those results are positive, it would support a direct indication for this patient population.

My advice is that HCPs who treat patients with resistant hypertension or PA keep up with these pivotal trials. We all saw how SGLT2 inhibitors were not well reimbursed and people were nervous about using them in the beginning. But now they are commonly prescribed and covered by health insurance because we have strong data demonstrating their clinical benefits. As with SLGT2 inhibitors, if the data support their use, ASIs will be integrated into the treatment paradigms for resistant hypertension. Ultimately, we need more positive data that will hopefully be forthcoming for HCPs to have a good level of comfort in prescribing ASIs.

Your Thoughts
Are you currently prescribing ASIs like baxdrostat in your practice? You can get involved in the conversation by answering the poll question and posting a comment below.

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