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Adhering to high blood pressure medication is important to lower the risks associated with uncontrolled hypertension. A novel drug being studied may lead to clues for developing safe medications with longer-lasting effects. Jovana Milanko/Stocksy
  • An investigational drug called zilebesiran has been found to be safe and effective in reducing systolic blood pressure in people with mild-to-moderate high blood pressure for up to six months with just one injection.
  • Over 1 billion people globally have high blood pressure. Hypertension places a person at a higher risk for various health issues throughout the body.
  • Many people have trouble adhering to their high blood pressure medication prescription, leaving them open to risks associated with uncontrolled hypertension.

An investigational drug called zilebesiran has been found to be safe and effective in reducing systolic blood pressure in people with mild-to-moderate high blood pressure for up to six months with just one injection.

These findings from the drug’s phase 2 clinical trial were recently presented at the American Heart Association’s Scientific Sessions 2023.

Over 1 billion people around the world have high blood pressure, medically known as hypertension.

Past studies show that having high blood pressure increases a person’s risk for several cardiovascular issues, such as stroke, heart failure, and atrial fibrillation.

Additionally, people with hypertension have a higher chance of kidney damage, metabolic syndrome, dementia, and vision issues.

High blood pressure is treated through medications and lifestyle changes, such as a healthy diet and increased physical activity.

However, previous research shows not all people with high blood pressure adhere to their prescribed medication, with many stopping taking the drugs after one year. This leaves them open to risks associated with uncontrolled hypertension.

According to Dr. George L. Bakris, professor of medicine and director of the American Heart Association Comprehensive Hypertension Center at the University of Chicago Medicine and lead author of this study, over 70% of people with hypertension either do not take their medications or do not take them as prescribed.

“Hence (we) have less than 30% of people with hypertension controlled in the country,” Dr. Bakris told Medical News Today. “This is in spite of the fact that we have over 100 antihypertensive medications for use.”

Dr. Cheng-Han Chen, a board certified interventional cardiologist and medical director of the Structural Heart Program at MemorialCare Saddleback Medical Center in Laguna Hills, CA — who was not involved in this study — agreed:

“It is thought that a large percentage of patients do not take their blood pressure medications as prescribed. When patients are not completely adherent to their medication regimen, (the) chances of their blood pressure not being under control increase, which in turn increases their risk of a cardiovascular event.

A big problem is simply the large number of prescribed medications that patients need to keep track of, some of which need to be taken multiple times a day.”

Dr. Jennifer Wong, a board-certified cardiologist and medical director of Non-Invasive Cardiology at MemorialCare Heart and Vascular Institute at Orange Coast Medical Center in Fountain Valley, CA, told MNT she has found that compliance with high blood pressure medication can be difficult with any daily medication that does not have an immediate tangible effect.

“Uncontrolled hypertension is a major risk factor for developing atherosclerotic diseases,” Dr. Wong continued. “And often it’s such a future event that many patients find it difficult to take …medication regularly. Every 10 mm drop in blood pressure can significantly reduce their risk for these diseases.”

Zilebesiran is an investigational RNA interference agent targeting angiotensinogen (AGT). AGT is a hormone mainly produced in the liver that helps regulate a person’s blood pressure.

“Zilebesiran blocks the message within the cell that stimulates (the) production of a substance called angiotensinogen,” Dr. Bakris explained. “This is the substance that is transformed into angiotensin II — (a) potent agent that causes arteries to constrict and raises blood pressure.”

“Angiotensin II has many purposes but, in excess, can raise blood pressure,” he added. “Thus, blocking its production reduces the likelihood of blood pressure elevation and will lower pre-existing high blood pressures.”

For this study, Dr. Bakris and his team recruited about 400 people with mild-to-moderate high blood pressure, defined as systolic blood pressure of 135-160 mm Hg. All participants were either untreated for high blood pressure or on stable therapy with up to two antihypertensive medications.

Study participants received either 150mg, 300mg, or 600mg doses once every six months, a 300mg dose once every three months of zilebesiran, or a placebo.

After six months, researchers found participants who received zilebesiran were significantly more likely to experience 24-hour average systolic blood pressure reductions of 20 mm Hg or more without needing to take additional high blood pressure medications.

Study participants taking zilebesiran were also more likely to reach 24-hour average systolic blood pressure measurements of 130 mm Hg or less at six months.

“I was pleasantly surprised that the effect lasted six months, but based on what I knew about the drug, I expected three months. Also, I did not expect the magnitude of the fall to be as great as 14-15 mm Hg, but more like 7-8 mm Hg, which is what the pills deliver. But then again, zilebesiran more effectively blocks the system.”

– Dr. George L. Bakris

After reviewing this research, Dr. Ian del Conde, cardiologist and director of vascular medicine at Miami Cardiac & Vascular Institute, part of Baptist Health South Florida, told MNT that this is an exciting study that marks a new era in the treatment of high blood pressure.

“I do not think most doctors anticipated a therapy such as this just a few years ago,” Dr. del Conde continued. “The idea that a chronic condition that is extremely prevalent in all societies in the world and has been clearly shown to increase the risk of premature death can be effectively and safely treated with a single injection administered every six months or so is a game changer.”

“[D]espite the availability of several classes of blood pressure-lowering drugs that are effective, safe, and expensive, there are still many patients who do not have our code for pressure control. Adherence or tolerance to the usual therapies is a common cause of uncontrolled blood pressure. This new treatment may change the way you treat high blood pressure in the future.”

Prof. Sir Nilesh Samani, Medical Director at the British Heart Foundation, also reviewed the study and told MNT:

“This study shows that an injection which could be given as little as twice a year is effective at lowering blood pressure. Further work is needed to show that it reduces heart attacks and strokes but if this is the case, then this could be a game-changing new treatment for high blood pressure.”

Dr. Chen told MNT that doctors do not currently have any effective blood pressure medications for such a long time after a single dose.

“This type of dosing interval gives us a tool to improve blood pressure over a prolonged period of time without having to rely on consistent daily medication adherence,” he added.

“This drug significantly lowered systolic blood pressure (by) at least 10 mm Hg on average, and sometimes 20 mm Hg or more on average,” Dr. Chen continued. “As the average systolic blood pressure at the start of this study was 142mmHg, this meant that a patient’s blood pressure could be brought to a ‘normal’ range simply with this injection, without the help of additional blood pressure medications.”