The Future of Hypertension Treatment: Promising New & Upcoming Therapies

Hypertension Management– Unmet Needs

Hypertension, which is commonly known as high blood pressure (BP), is the primary cause of death and years lost to disability. Perhaps something like high BP relentlessly claims lives and fuels disability worldwide, standing as a leading risk factor for debilitating conditions like heart disease, stroke, and dementia (Redon et al,2024).¹

However, despite the wide availability of various classes of medications, the incidence of high BP continues to increase. (Kanbay et al,2023).² Also, a significant portion either do not respond or are resistant to these treatment options. Resistant hypertension is a critical form of high BP associated with a higher risk of complications and death. The American Heart Association describes resistant hypertension as a state in which BP continues to exceed the target range despite the administration of three or more high BP medications from different classes, including a diuretic, at their highest tolerated doses (Naseralallah et al,2024).³ Thus, there is a renewed interest in new and upcoming innovative therapies for the management of High BP that can effectively lower BP, some of which are discussed here.

Newly Approved Therapies

Recently, the U.S. Food and Drug Administration (FDA) has approved a new drug, Aprocitentan, to treat hypertension, specifically in conjunction with other medications, for patients whose BP is not adequately managed by current treatments. Additionally, renal denervation, a procedure, is being recognized as a potential solution for resistant hypertension. We hereby discuss a few key points.

Aprocitentan (ET Receptor Antagonist)

Aprocitentan (TRYVIO™) is an oral medication that acts as a dual antagonist for endothelin A (ETA) and B (ETB) receptors. Idorsia Pharmaceuticals has developed it specifically to treat resistant hypertension. Moreover, this drug is designed to focus on the endothelin (ET) pathway, “a pathway largely untouched by current therapies,” for resistant hypertension.

Approval

• In March 2024, the U.S. Food and Drug Administration (FDA) approved Aprocitentan for the treatment of hypertension in combination with other antihypertensive drugs to lower BP in adults with resistant hypertension (who are not adequately controlled by other drugs).
• It was approved based on the results of the Phase 3 PRECISION trial.
• Consequently, the PRECISION trial demonstrated that Aprocitentan effectively reduces BP in patients with resistant hypertension, underscoring the need for additional studies to evaluate its long-term safety and broader clinical applications.

Mechanism of action

• Endothelin-1 (ET-1) is a natural chemical made by the body that causes blood vessels to tighten or narrow. When blood vessels become narrow, it increases BP.
• Aprocitentan is a medicine that blocks the effects of ET-1. It does this by preventing ET-1 from attaching to receptors ETA and ETB on blood vessels. As a result, the blood vessels stay more relaxed and open, which helps to lower BP (Figure 1).

Figure 1: Mechanism of Action of Aprocitentan

Safety Profile

• The most common adverse reactions reported are edema (swelling) and fluid retention, as well as anemia.
• Also, Aprocitentan may cause serious birth defects, so it is not allowed to be taken during pregnancy. In addition, you should avoid becoming pregnant during treatment with Aprocitentan and continue using effective contraception for one month after stopping the medication, to prevent potential harm to the fetus.
• Aprocitentan has the potential to lead to liver damage or toxicity. Therefore, patients who are at a higher risk should be made aware of the symptoms of liver toxicity and urged to quickly reach out to their healthcare provider if they experience any signs.

Dosage Form and Strength

• It is available as a 12.5 mg tablet for oral use.

Dosage and Administration

• The recommended dosage is 12.5 mg orally once daily, with or without food.

(Naseralallah et.al,2024 ³; Dhillon et.al.,2024 ⁴ ;Tryvio ⁵; Riaz et.al.,2025 ⁶)

Renal Denervation (Device-Based Therapy)

In November 2023, the U.S. FDA approved two renal (kidneys) denervation systems for the treatment of hypertension. Additionally, the FDA’s approval of renal denervation represents a significant milestone in hypertension treatment, introducing a novel therapeutic option for individuals with resistant hypertension.

Mechanism of Action

• Renal denervation involves the selective destruction or interruption of renal nerves of the renal arteries (blood vessels that supply the kidneys).
• These renal nerves are part of the sympathetic nervous system, which plays a major role in regulating BP.
• In patients with hypertension, particularly resistant hypertension, there’s often an overactivity of the renal sympathetic nervous system.
• Renal denervation aims to disrupt or destroy these overactive sympathetic nerves.

Procedure

Figure 2: Renal Denervation Procedure

• The procedure is generally performed under local anesthesia and conscious sedation to lessen pain.
• During the process of renal denervation, a catheter is inserted into the femoral artery, located in the groin, and navigated to the renal arteries.
• Once correctly positioned, the catheter administers radiofrequency energy or ultrasound to ablate/destroy/burn the nerve fibers around the renal arteries (Figure 2).
• The primary objective is to reduce the activity of these nerves, which may be excessively active in individuals with hypertension, leading to increased BP.

(Zhang etal,2025 ⁷; Cluett et.al,2024 ⁸)

• Pros (Advantages)
  • May lower BP when medicines don’t work well
  • One-time procedure (no daily pills required)
  • Minimally invasive (done through a small puncture, not surgery)
  • Safe and well-tolerated in most studies
  • No major recovery time – quick return to daily activities

• Cons (Limitations)
  • Not suitable for everyone
  • Still not widely available in all countries
  • Some risk of bleeding or injury at the catheter site
  • May not work for all patients
  • Long-term effects still being studied
  • May need to continue BP medications in some cases

Therapies in the Pipeline

Several innovative therapies for hypertension are emerging, such as mineralocorticoid receptor antagonists and aldosterone synthase inhibitors. Moreover, device-based therapies are showing potential, especially for resistant hypertension. Here’s a brief look at a few of the upcoming therapies.

Finerenone

• Finerenone, known by its brand name Kerendia, was granted approval by the US FDA in July 2021 for the management of chronic kidney disease (CKD) in adult patients with type 2 diabetes. Furthermore, it obtained approval from the European Medicines Agency in February 2022.
• In recent research, Finerenone has shown positive results in patients suffering from resistant hypertension.
• Finerenone serves as a nonsteroidal selective mineralocorticoid antagonist. It works by blocking the effects of aldosterone, a mineralocorticoid.
• Aldosterone causes the kidneys to retain sodium and water, resulting in increased blood volume and elevated BP. 
• Finerenone, by blocking the action of aldosterone, helps the kidneys excrete more sodium and water, which subsequently lowers BP.
• Although Finerenone is currently not recognized as a first-line treatment for hypertension, its ability to protect organs makes it an important adjunct therapy for specific individuals, especially those with CKD, diabetes, or resistant hypertension.

(Nyamagoud et.al.,2023 ⁹)

Lorundrostat

• Lorundrostat is a novel oral medication that acts as a highly selective inhibitor of aldosterone synthase, currently under development by Mineralys Therapeutics for addressing uncontrolled hypertension.
• Aldosterone is a hormone that plays a crucial role in regulating BP and maintaining electrolyte balance. In certain instances, an overproduction of aldosterone can lead to hypertension. Thus, by inhibiting aldosterone synthase, Lorundrostat lowers aldosterone levels and helps to control BP.
• In Phase 3 clinical trials (Launch-HTN trial ), Lorundrostat has revealed promising findings for cases of uncontrolled or resistant hypertension.
• Lorundrostat 50 mg, administered once daily, showed clinically meaningful and sustained reductions in systolic BP, with a 16.9 mmHg decrease at Week 6 and a 19.0 mmHg decrease at Week 12.

(Laffin,2023 ¹⁰ ; Lapoce,2025¹¹)

Baxdrostat

• Baxdrostat is another strong aldosterone synthase inhibitor.
• The Phase 2 trial, BrigHTN, demonstrated robust efficacy in managing treatment-resistant hypertension, with a systolic BP decrease of up to 20 mmHg at 2 mg compared to placebo.
• However, in another Phase 2 trial, the HALO Baxdrostat failed to achieve the primary endpoint.
• The ongoing phase 3 BaxHTN trial aims to assess the safety profile of baxdrostat and its influence on BP among patients experiencing uncontrolled or resistant hypertension. The results are projected to be released in late 2025.

(BrigHTN,2022¹²; HALO,2023 ¹³; Shira et.al,2024 ¹⁴)

Zilebesiran

• Zilebesiran represents a novel RNA interference therapy that is being explored for the management of hypertension.
• Zilebesiran utilizes RNA interference technology to reduce the synthesis of angiotensinogen, a protein essential to the Renin-Angiotensin-Aldosterone System (RAAS), which regulates BP.
• When administered via subcutaneous injection, Zilebesiran exhibited prolonged BP reductions over 6 months following a single dose in patients with hypertension who were not on any antihypertensive medications.
• Further, ongoing Phase 3 trials are assessing its effectiveness as an add-on therapy for individuals with uncontrolled hypertension who also carry a high cardiovascular risk.

(Desai et.al.,2023 ¹⁵; Laffin,2023 ¹⁰)

Firibastat

• Firibastat, an inhibitor of brain aminopeptidase A, is being developed by Quantum Genomics. Also, It represents a first-in-class medication that acts within the brain to control BP levels. It may provide a new method for treating patients with resistant hypertension.
• Nonetheless, two recent phase 3 open-label multicenter studies assessing the efficacy and safety of Firibastat in patients with difficult-to-treat hypertension (FRESH and REFRESH) have not succeeded in lowering BP in cases of resistant hypertension.

(Alomar et.al,2021 ¹⁶; Redon et.al,2024 ¹)

Key Takeaway

The range of therapies available for managing high BP has evolved significantly, marked by the introduction of medications that can affect the primary mechanisms contributing to the onset and maintenance of hypertension. Although lifestyle changes are fundamental, these innovations hold the potential for more individualized and effective care, particularly for patients who struggle with standard treatments.

Further Reading

1. Redon, J., & Carmena, R. (2024). Present and future of drug therapy in hypertension: An overview. Blood Pressure, 33(1), 2320401. https://doi.org/10.1080/08037051.2024.2320401
2. Kanbay, M., Copur, S., Tanriover, C., Ucku, D., & Laffin, L. (2023). Future treatments in hypertension: Can we meet the unmet needs of patients? European Journal of Internal Medicine, 115, 18–28. https://pubmed.ncbi.nlm.nih.gov/37330317
3. Naseralallah, L., & Koraysh, S. (2024). Aprocitentan: A new emerging prospect in the pharmacotherapy of hypertension. Blood Pressure, 33(1), 2424824. https://doi.org/10.1080/08037051.2024.2424824
4. Dhillon, S. (2024). Aprocitentan: First approval. Drugs, 84(7), 841–847. https://pubmed.ncbi.nlm.nih.gov/38833193
5. Idorsia Pharmaceuticals Ltd. (n.d.). Tryvio® (aprocitentan). https://www.tryvio.com
6. Riaz, R., Ahmed, U., Naqi, U., Afaq, L., Shaukat, A., Khan, Y., & Akilimali, A. (2025). Aprocitentan in hypertension management: Clinical efficacy, safety, and future prospects. Annals of Medicine and Surgery (London), 87(3), 1472–1478. https://doi.org/10.1097/MS9.0000000000006477
7. Zhang, J., Belford, P. M., & Stouffer, G. A. (2025). Renal denervation after USA FDA approval: An update from an interventional cardiologist’s perspective. Journal of Clinical Medicine, 14(10), 3554. https://doi.org/10.3390/jcm14103554
8. Cluett, J. L., Blazek, O., Brown, A. L., East, C., Ferdinand, K. C., Fisher, N. D. L., Ford, C. D., Griffin, K. A., Mena-Hurtado, C. I., Sarathy, H., Vongpatanasin, W., & Townsend, R. R.; American Heart Association Council on Hypertension; Council on Cardiovascular and Stroke Nursing; Council on the Kidney in Cardiovascular Disease; & Council on Peripheral Vascular Disease. (2024). Renal denervation for the treatment of hypertension: A scientific statement from the American Heart Association. Hypertension, 81(10), e135–e148. https://doi.org/10.1161/HYP.0000000000000253
9. Nyamagoud, S. B., Viswanatha Swamy, A. H., Hiremath, J., Abhishek, A. B., Raj, S., Hegde, M., et al. (2023). Finerenone as a new potent resistant hypertension agent: A review. International Journal of Pharmaceutical Investigation, 14(1), 10–15. https://doi.org/10.5530/ijpi.14.1.3
10. Laffin, L. J. (2024). Future of antihypertensive therapies. Circulation, 150(25), 1987–1989. https://doi.org/10.1161/CIRCULATIONAHA.124.072036
11. The American Journal of Managed Care. (2023). Lorundrostat significantly lowers blood pressure in key hypertension trials. https://www.ajmc.com/view/lorundrostat-significantly-lowers-blood-pressure-in-key-hypertension-trials
12. Cardiac Vascular News. (2022). CinCor Pharma announces positive topline data for phase 2 BRIGHTN trial evaluating baxdrostat, its selective aldosterone synthase inhibitor, in treatment-resistant hypertension. https://cardiacvascularnews.com/cincor-pharma-announces-positive-topline-data-for-phase-2-brightn-trial-evaluating-baxdrostat-its-selective-aldosterone-synthase-inhibitor-in-treatment-resistant-hypertension
13. The American Journal of Managed Care. (2023). HALO misses end point but optimism remains for baxdrostat in resistant hypertension. https://www.ajmc.com/view/halo-misses-end-point-but-optimism-remains-for-baxdrostat-in-resistant-hypertension
14. Perl, S., Azizi, M., Bakris, G., Brown, J. M., Flack, J. M., Jones, E., Shibata, H., Wittes, J., Wilderäng, U., Olsson, D. S., & Williams, B. (2024). Rationale and design of phase 3 trial for baxdrostat, a novel highly selective aldosterone synthetase inhibitor. Journal of Hypertension, 42(Suppl 1), e259–e260. https://doi.org/10.1097/HJH.0000000000003965
15. Desai, A. S., Webb, D. J., Taubel, J., Casey, S., Cheng, Y., Robbie, G. J., Foster, D., Huang, S. A., Rhyee, S., Sweetser, M. T., & Bakris, G. L. (2023). Zilebesiran, an RNA interference therapeutic agent for hypertension. The New England Journal of Medicine, 389(3), 228–238. https://doi.org/10.1056/NEJMoa2303264
16. Alomar, S. A., Alghabban, S. A., Alharbi, H. A., Almoqati, M. F., Alduraibi, Y., & Abu-Zaid, A. (2021). Firibastat, the first-in-class brain aminopeptidase A inhibitor, in the management of hypertension: A review of clinical trials. Avicenna Journal of Medicine, 11(1), 1–17. https://doi.org/10.1055/s-0040-1719177.

Share on Facebook

Post on X

Follow us