Game-Changing Blood Pressure Drug Works for Patients Not Controlled by Standard Treatments

Researchers have found that a long-acting injection, given just twice a year alongside standard drugs.

Blood pressure is one of the most common health problems worldwide, yet it remains difficult to control for many patients even with daily medication. New research from the United Kingdom suggests a different approach could help. Scientists report that a treatment given just twice a year may offer sustained blood pressure reductions for people whose hypertension has proven hard to manage.

The findings come from a large international clinical trial published in JAMA and led by researchers at Queen Mary University of London. The study focused on a long-acting injectable therapy designed to work alongside existing blood pressure medications rather than replace them.

A Twice-Yearly Option for Hypertension

The trial, known as KARDIA-2, enrolled 663 adults whose blood pressure remained above recommended levels despite standard treatment. All participants continued taking their usual medications. Some also received an injection of an investigational drug called zilebesiran once every six months.

Researchers found that patients who received zilebesiran experienced greater and more consistent reductions in blood pressure than those who remained on standard therapy alone. The results suggest that long-acting treatments could help close the gap for patients who struggle to achieve adequate control with daily pills.

Why Long-Lasting Treatments Matter

High blood pressure is often called a silent condition because it rarely causes symptoms until serious damage has occurred. In the UK, around one in three adults lives with hypertension, a major contributor to heart attacks and strokes. Managing the condition typically requires taking medication every day, sometimes multiple times a day, which can be challenging over the long term.

A treatment that works for months at a time could reduce the burden of daily dosing and help maintain more stable blood pressure levels. For patients who miss doses or need additional support, this kind of approach could make a meaningful difference.

Expert Perspective

Dr. Manish Saxena, Clinical Co-Director of the William Harvey Clinical Research Centre at Queen Mary University of London and a hypertension specialist at Barts Health NHS Trust, was the UK lead investigator and senior author of the study. He emphasized both the scale of the problem and the potential impact of the findings:

“Hypertension is a global health concern as blood pressure control rates remain poor, and is a leading cause of heart attacks and strokes. This study demonstrates the efficacy and safety of zilebesiran, when added to commonly used first-line blood pressure-lowering drugs. The novelty of this treatment is its long duration; giving just one injection every six months could help millions of patients to better manage their condition.”

How the Treatment Works

Zilebesiran uses RNA interference technology to target a key process involved in blood pressure regulation. The drug reduces the production of a liver protein called angiotensinogen (angiotensinogen), which plays a central role in tightening blood vessels. Lower levels of this protein allow blood vessels to relax, leading to reduced blood pressure. The medication is administered as an injection under the skin.

What Comes Next

Researchers are now preparing to test the therapy in broader and higher-risk groups. A follow-up Phase 2 trial, KARDIA-3, will examine whether zilebesiran could benefit people with high blood pressure who already have cardiovascular disease or who face an elevated risk of developing it.

The study sponsor also plans to launch a large global outcomes trial. That research will focus on whether long-term treatment with zilebesiran can reduce serious events such as heart attacks, strokes, and deaths from cardiovascular disease. If successful, the approach could mark a shift in how chronic blood pressure management is delivered.

Reference: “Add-On Treatment With Zilebesiran for Inadequately Controlled Hypertension: The KARDIA-2 Randomized Clinical Trial” by Akshay S. Desai et al, 28 May 2025, JAMA.
DOI: 10.1001/jama.2025.6681

The study was funded by Alnylam Pharmaceuticals, with Barts Health NHS Trust serving as a lead site for the trial and top European enroller on the study.

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