A new review published in The Lancet has highlighted emerging long-acting therapies for hypertension that may allow patients to receive just two injections per year instead of taking daily oral medications. The development could represent a significant shift in blood pressure management, particularly for patients who struggle with taking medications daily.
Hypertension, or high blood pressure, is one of the leading risk factors for cardiovascular disease worldwide. According to the World Health Organization, an estimated 1.28 billion adults aged 30–79 years globally have hypertension. Nearly half are unaware of their condition, and only about one in five have it under control.
The WHO notes that hypertension contributes significantly to heart attacks, strokes, kidney failure, and premature death. Poor adherence to daily medication is one of the major barriers to effective blood pressure control.1
The therapies discussed in the Lancet review include long-acting injectable medications designed to suppress components of the renin-angiotensin-aldosterone system (RAAS), a hormonal system that regulates blood pressure and fluid balance.
Some of the investigational drugs function by:
Targeting angiotensinogen production in the liver using RNA interference (RNAi) technology
Reducing levels of angiotensin II, a hormone that narrows blood vessels
Producing sustained vasodilation (widening of blood vessels)
Lowering overall systemic blood pressure
By acting upstream in the RAAS pathway, these therapies may provide prolonged blood pressure reduction after a single injection.
RNA-based therapies work by “silencing” specific genes responsible for producing proteins involved in blood pressure regulation. This approach has already been used in other chronic conditions, including lipid disorders. 2
See also: Smartwatch Alert Helps Detect Hypertensive Crisis in 26-Year-Old
Daily oral antihypertensive medications are effective when taken consistently. However, studies show that long-term adherence can be challenging due to forgetfulness or while taking multiple medications.
According to coverage of the Lancet review, these therapies are currently in various stages of clinical development. Early trials have demonstrated sustained reductions in blood pressure over several months.
Safety monitoring in clinical studies has focused on:
Injection site reactions
Electrolyte balance
Kidney function
Long-term hormonal effects
As of now, the treatments are not widely available and remain under regulatory evaluation. Larger phase trials are ongoing to assess long-term cardiovascular outcomes and safety profiles.
Speaking to MedBound Times, Dr. Hari Kishan Boorugu, Consultant Physician and Diabetologist at Yashoda Hospitals, Hyderabad, clarified that zilebesiran is an antihypertensive therapy recently developed.
Dr. Boorugu explained that zilebesiran works by targeting the renin–angiotensin–aldosterone system (RAAS) at the level of the liver. Using RNA interference technology, it reduces the production of angiotensinogen, a precursor protein involved in blood pressure regulation. Because it acts upstream in the RAAS pathway, its effects can last for three to six months after a single injection.
However, current evidence remains limited to phase II clinical trials. In studies comparing zilebesiran to placebo, systolic blood pressure was reduced by approximately 10 mmHg, which he described as a modest reduction. When evaluated as an add-on therapy alongside existing RAAS blockers such as ACE inhibitors, the additional reduction was around 5 mmHg, which may not be clinically significant.
Dr. Boorugu also highlighted safety considerations. Similar to other RAAS-blocking drugs, zilebesiran has been associated with risks such as hyperkalemia (elevated potassium levels) and hypotension. A key concern is its prolonged duration of action. Unlike ACE inhibitors or angiotensin receptor blockers, which can be discontinued before surgery or acute illness, this long-acting injectable cannot be rapidly reversed. In situations involving dehydration, blood loss, or major surgery, suppression of the RAAS pathway could increase the risk of severe hypotension or acute kidney injury. Currently, there is no specific antidote to reverse its effects, and management would rely on supportive measures such as intravenous fluids and vasopressor medications.
He emphasized that phase III data are still pending, and long-term safety, cost, cardiovascular outcomes, and real-world effectiveness remain unknown. At present, he noted, the therapy remains investigational and should be viewed as an early-stage development rather than an immediate replacement for established antihypertensive treatments.
With hypertension affecting over a billion people worldwide, innovations that simplify treatment regimens may help address gaps in care.
The WHO emphasizes that improving detection, treatment adherence, and long-term control remains critical in reducing cardiovascular mortality globally.
Long-acting injectable therapies could be particularly relevant in:
Rural or underserved regions
Populations with limited follow-up access
Patients with poor medication adherence
Further research will determine cost-effectiveness and integration into national hypertension programs.
References
World Health Organization. “Hypertension.” WHO Newsroom. Accessed February 2026. https://www.who.int/news-room/fact-sheets/detail/hypertension.
Kronborg, Camilla S., Morten Bøttger, Mikkel B. Kramer, Charlotte H. Nielsen, Allan Flyvbjerg, and Peter Rossing. “Long-Acting Therapies for Hypertension: A Review.” The Lancet (2026). https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(25)02064-1/abstract.