Twice-Yearly Injections May Transform Hypertension Treatment, Lancet Review Finds

Treatment for high blood pressure which has long depended on daily pills could soon move to just two injections a year, according to a new review in The Lancet that outlines late-stage therapies now in global trials. The development could fundamentally change how hypertension is managed, particularly at a time when control rates remain alarmingly low despite decades of available medicines.

The review highlights emerging treatments that act upstream in the disease pathway rather than simply lowering numbers. One of the most advanced candidates, Zilebesiran, being developed by Roche and Alnylam Pharmaceuticals, uses small interfering RNA (siRNA) technology to suppress the liver's production of angiotensinogen, a protein central to blood pressure regulation. By dampening this pathway, the drug can reduce blood pressure for up to six months after a single injection. It is currently in phase 3 trials following promising mid-stage results.

Clinical trials of investigational agents have shown that one subcutaneous injection can lower systolic blood pressure for up to six months. Mid-stage findings, some also reported in the New England Journal of Medicine, demonstrated meaningful and sustained reductions.

Another investigational therapy, Ziltivekimab from Novo Nordisk, targets inflammatory pathways increasingly linked to cardiovascular risk, aiming to reduce both blood pressure and broader vascular damage. Additional strategies are exploring more precise control of aldosterone, a hormone that regulates salt and water balance and increases blood volume and pressure.

The review notes that poor adherence to daily medication remains one of the largest barriers to effective hypertension control globally. Long-acting injectables could help bridge this gap if ongoing studies confirm safety and durability. The appeal of twice-yearly injections lies in their durability and ability to ensure consistent drug exposure, potentially improving long-term control and reducing heart attacks and strokes.

Hypertension remains the leading cause of heart attacks, strokes and premature deaths worldwide. The World Health Organization defines it as blood pressure at or above 140 mm Hg systolic and/or 90 mm Hg diastolic, while normal levels are below 120/80 mm Hg. Globally, an estimated 1.4 billion adults aged 30 to 79 live with hypertension, with nearly 44 per cent unaware of their condition. Among those diagnosed, fewer than one in four have their blood pressure under control.

India mirrors the crisis. The Indian Council of Medical Research-INDIAB study in 2023 estimated that 315 million Indians, or 35.5 per cent of the population, have hypertension. Data from National Family Health Survey-5 showed that nearly half of hypertensive men and over a third of hypertensive women in the country do not have adequate control.

For decades, treatment has relied on combinations of daily oral drugs such as ACE inhibitors, angiotensin receptor blockers, calcium channel blockers and thiazide diuretics. While effective in theory, adherence remains a major challenge, especially as many patients also manage diabetes, obesity or cholesterol disorders requiring multiple medications.

Early trials suggest a favourable safety profile, but researchers caution that hypertension is a lifelong condition and that these therapies remain under clinical evaluation and are not yet ready to replace standard treatment. Long-term cardiovascular outcome studies and large-scale safety data will be essential before widespread rollout. If someone develops an adverse reaction months after receiving a long-acting drug, managing that becomes complex. Long-term safety data across diverse populations is essential.

Affordability could also shape accessibility. Long-acting injectables in other cardiovascular domains have entered the market at high price points, raising concerns about equitable access, particularly in low- and middle-income countries where hypertension rates are highest. The example of inclisiran, an injectable cholesterol-lowering drug introduced in India in 2024 at an annual cost of Rs 1.8 lakh to Rs 2.4 lakh, underscores affordability concerns.

A director at Plexus Cardiac Care said the field may be approaching a structural shift in how hypertension is treated. These therapies are designed to act at the biological source of high blood pressure rather than repeatedly countering its effects. Injectable treatment for hypertension has the potential to significantly improve real-world control rates by eliminating missed daily doses, which is one of the biggest barriers in hypertension management globally. This represents more than just a new drug, it signals the beginning of a precision cardiovascular era, where treatment is longer-acting, more predictable and designed around real-world patient behavior.

A senior cardiologist at AIIMS Delhi urged caution in interpreting the development as a breakthrough. The bigger challenge in hypertension control is access to affordable healthcare. Unless care is accessible and affordable, patients do not return for regular follow-ups, diagnosis remains delayed, and treatment continuity suffers. Strengthening primary care systems, expanding wellness centres and increasing the number of general physicians may have a far greater impact on blood pressure control than introducing high-cost therapies. These injectables may benefit a segment of patients, but to suggest they are the solution to uncontrolled hypertension globally would be premature. While conventional antihypertensive therapies have robust evidence showing reduction in heart attacks and strokes, similar long-term cardiovascular outcome data for these newer agents is still evolving.

Specialists stress that while early trial results are encouraging, robust long-term data across diverse populations will be essential before widespread adoption. If proven safe, effective and affordable, twice-yearly injections could mark a decisive shift in preventive cardiology, easing the treatment burden for millions worldwide.