What is it about?
High blood pressure is one of the leading causes of heart disease, stroke, kidney disease, and early death worldwide. Many people still have high blood pressure even after taking several medications. This is called uncontrolled or resistant hypertension. Our study looked at a new group of medicines called aldosterone synthase inhibitors. These medicines work by reducing the body’s production of aldosterone, a hormone that can make the body retain salt and water, raise blood pressure, and contribute to damage in the heart, blood vessels, and kidneys. We reviewed and combined evidence from randomized clinical trials that tested three aldosterone synthase inhibitors: baxdrostat, lorundrostat, and osilodrostat/LCI699. We compared how well these medicines lowered blood pressure and also examined their safety. Overall, the medicines lowered systolic blood pressure meaningfully compared with placebo. Baxdrostat and lorundrostat showed strong effects, especially in resistant hypertension. Osilodrostat/LCI699 also showed benefit, although some findings came from smaller early-stage studies. The medicines were generally not linked to more serious adverse events, but they did increase the risk of low blood pressure and electrolyte problems, especially high potassium levels.
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Why is it important?
This work is important because many patients with hypertension remain above target blood pressure despite using existing treatments. Resistant hypertension is especially difficult to manage and is linked to a higher risk of stroke, heart failure, kidney disease, and other cardiovascular complications. Aldosterone synthase inhibitors may offer a more targeted treatment option for patients whose high blood pressure is partly driven by excess aldosterone activity. By comparing these drugs across different hypertension types, our study helps clarify where they may be most useful and what safety issues clinicians should monitor. The findings suggest that these medications could become valuable additions to hypertension care, but they should be used with careful monitoring of blood pressure, potassium, and sodium levels. Longer studies are still needed to confirm their long-term safety and whether they reduce major outcomes such as stroke, heart failure, kidney failure, and cardiovascular death.
Perspectives
As researchers and clinicians interested in cardiovascular prevention, we see this study as part of a broader shift toward more precise treatment of hypertension. Instead of treating all uncontrolled blood pressure the same way, future care may increasingly consider the biological drivers behind each patient’s condition. Our findings suggest that aldosterone synthase inhibition is a promising strategy, particularly for patients with resistant hypertension. However, the safety signals also remind us that powerful blood pressure treatments must be paired with careful clinical monitoring. The next step is to determine which patients benefit most, how these drugs perform over longer periods, and whether they improve real-world cardiovascular outcomes.
Micah Okwah
Yale University
Read the Original
This page is a summary of: Aldosterone synthase inhibitors in uncontrolled and resistant hypertension: A phenotype-stratified systematic review and network meta-analysis of randomized trials, PLOS One, June 2026, PLOS,
DOI: 10.1371/journal.pone.0349932.
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