• Posted July 20, 2023

Experimental Shot Given Every Six Months Controlled High Blood Pressure in Early Trial

Every day, millions of people must take one or more pills to control their blood pressure and reduce their risk for heart attack or stroke, but if new research pans out, some may be able to scrap their pills for a twice-yearly shot with the same benefits.

Given as a shot every six months, zilebesiran suppresses the gene that produces a hormone called angiotensin that causes blood vessels to contract. This contraction causes blood pressure to rise.

The new shot isn't ready for prime time yet, but phase 2 trials are underway.

“This approach offers the potential for sustained reduction in blood pressure that may obviate the need for daily pills in select patients and may help overcome some of the challenges with adherence that compromise our ability to effectively treat high blood pressure,” said lead author Dr. Akshay Suvas Desai, medical director of the Cardiomyopathy and Heart Failure Program at Brigham and Women's Hospital in Boston.

Many people with high blood pressure miss or skip pills because they are overwhelmed and don't necessarily feel sick, among other reasons.

For the study, 107 people with high blood pressure received either varying doses of zilebesiran as a shot, or a placebo injection, and were then followed for 24 weeks.

The researchers also looked at the effect of the 800-mg dose of zilebesiran on blood pressure when people ate a low- or high-salt diet. Another arm of the study looked at how well the shot worked when it was combined with another blood pressure-lowering medication.

The higher the dose, the greater the effects on blood pressure, with results lasting for up to six months, the study showed. The shot was even more effective when paired with a low-salt diet or another medication. The new trial was funded by Alnylam Pharmaceuticals, the Cambridge, Mass.-based maker of zilebesiran.

“This compound does what we hoped it would do, and blood pressure reduction lasts,” Desai said. “Patients may be able to come into the office quarterly or on a biannual basis to manage blood pressure."

He called the findings exciting but said researchers are eager to learn more.

"We need more data to tell us if this approach will reduce rates of heart failure, stroke and heart attacks,” Desai said.

Zilebesiran likely won't be the only blood pressure-lowering medication that people need, he noted.

“It may provide a nice background of blood pressure control on which other medications can be layered,” Desai said.

The new study assuages concerns that such a long-acting medication might make blood pressure dip too low.

“Putting a person on a high-salt diet can help reverse the effects,” Desai said. There are also medications available to reverse the effects of low blood pressure.

Study co-author Dr. George Bakris called the approach "very feasible" for managing high blood pressure.

“The advantages are that it is given as one injection, is good for six months, and you are going to get a substantial drop in blood pressure that would be equivalent to a high dose of a commonly used blood pressure drug,” said Bakris, director of the University of Chicago Comprehensive Hypertension Center.

So far, there don't seem to be many side effects, he said.

“It's not a substitute for pills, but it can reduce pill count and improve adherence,” Bakris said.

The study was published July 20 in the New England Journal of Medicine.

Dr. Maria Carolina Delgado-Lelievre, director of the University of Miami Comprehensive Hypertension Center, said more research is needed before anyone can start to think about downsizing their pill boxes.

“Diet and lifestyle changes remain fundamental for managing blood pressure effectively, even with the use of medication like zilebesiran,” said Delgado-Lelievre, who reviewed the findings.

Certain poor lifestyle choices, such as consuming too much salt, can reduce the effectiveness of blood pressure medications, she pointed out.

“Zilebesiran is not exempt from this phenomenon, as their results indicate that individuals exposed to a high-salt diet saw their blood pressure return to baseline levels,” Delgado-Lelievre said. “Adopting a heart-healthy diet and lifestyle is vital to complement the benefits of medication.”

High blood pressure is the No. 1 risk factor for heart disease and stroke.

“The concerning issue is that despite various classes of hypertensive medications and advancements in medical technologies, only 1 in 4 adults with hypertension have their condition under control,” Delgado-Lelievre said. “This highlights the critical need to effectively manage blood pressure to reduce the risk of serious complications like heart disease and stroke, ultimately improving overall health and well-being.”

More information

Learn how to lower your blood pressure at the American Heart Association.

SOURCES: Akshay Suvas Desai, MD, MPH, medical director, Cardiomyopathy and Heart Failure Program, Advanced Heart Disease Section, Brigham and Women's Hospital, Boston; George Bakris, MD, professor, medicine, director, University of Chicago Medicine Comprehensive Hypertension Center; Maria Carolina Delgado-Lelievre, MD, assistant professor, University of Miami School of Medicine, and director, University of Miami Comprehensive Hypertension Center; New England Journal of Medicine, July 20, 2023