New Delhi: The results of a late-stage clinical trial of a breakthrough treatment for hard-to-control hypertension—blood pressure that does not respond even to multiple therapies— have cardiologists across many countries hopeful.
Baxdrostat, an experimental drug by British-Swedish pharmaceutical major AstraZeneca, has shown in phase three clinical trials to significantly lower blood pressure in people whose levels remain dangerously high despite taking several medicines.
The results offer hope to patients who are at a high risk of cardiovascular events such as heart attacks, strokes, kidney complications and early death despite taking medication for controlling blood pressure.
The results of the BaxHTN study, whose first arm involved 796 patients from 214 sites worldwide, showed that after 12 weeks, patients taking baxdrostat saw their systolic blood pressure fall by about 9-10 mmHg (millimetres of mercury, the unit of measurement of blood pressure) more than those given a placebo–a reduction significant enough to cut cardiovascular risks.
Hypertension, or high BP, occurs when the pressure in the blood vessels is too high–140/90 mm Hg or higher. The first number, known as systolic pressure, measures pressure created as blood pumps out of the heart and into the arteries. Diastolic pressure is the pressure created as the heart rests between heartbeats.
The results of the BaxHTN trial were presented at the European Society of Cardiology Congress 2025 and simultaneously published in the New England Journal of Medicine last week.
Dr Bryan William, chair of medicine at University College London and chief investigator of the trial, said that the findings demonstrate baxdrostat’s potential in tackling one of the toughest challenges in cardiovascular care–hypertension that is hard to control despite multiple therapies.
“Achieving a nearly 10 mmHg placebo-adjusted reduction in systolic blood pressure with baxdrostat in the BaxHTN phase 3 trial is exciting, as this level of reduction is linked to substantially lower risk of heart attack, stroke, heart failure and kidney disease,” Dr William said in a statement.
Big hope
A large proportion of hypertensive adults, despite diligent clinical management, fail to achieve their recommended blood pressure treatment targets despite three antihypertensive medications. They sometimes require four or more medications to achieve their targets.
In such cases, the condition is categorised as hard-to-control, stubborn, uncontrolled or resistant hypertension.
It is estimated that nearly 50 percent of patients in the US being treated for hypertension still do not have their blood pressure under control despite lifestyle changes and the use of multiple medications.
Though there is no large-scale estimate for Indians with hard-to-control hypertension, scientists say nearly 10 percent have resistant hypertension.
A 2023 large study by the Indian Council of Medical Research (ICMR) and the Madras Diabetes Research Foundation (MDRF) showed that India has 31.5 crore people with hypertension. But it was also estimated that fewer than 10 percent of people with hypertension had their blood pressure under control in 2019-21.
According to recent guidelines, diagnosis of hypertension typically requires at least two BP-lowering medications, as monotherapy effectively achieves optimal BP control for only about 30 percent of patients.
Current recommendations advocate combination therapy as a first-line treatment in most adults, particularly patients with comorbid conditions that require rapid BP reduction.
These combinations usually include an angiotensin-converting enzyme (ACE) inhibitor such as perindopril, which relaxes blood vessels; or an angiotensin II receptor blocker (ARB) paired with a calcium channel blocker (CCB) such as amlodipine, which prevents calcium from entering the heart’s muscle cells and blood vessels; or a thiazide or thiazide-like diuretic such as indapamide, which treats hypertension by increasing the excretion of water and salt from the body.
A key contributor to hard-to-control hypertension is aldosterone, a hormone that raises blood pressure by promoting sodium and water retention.
Elevated aldosterone levels, along with factors such as obesity, high salt intake and various genetic or secondary conditions, are strongly associated with poor blood pressure control.
Heart specialists are keenly watching the trial results which have shown that baxdrostat significantly lowers aldosterone levels. “This is a first-in-class drug and an important addition in the armamentarium of drugs used for management of difficult-to-treat hypertension,” Dr Ambuj Roy, senior interventional cardiologist with the All India Institute of Medical Sciences (AIIMS), told ThePrint.
He said the therapy helps inhibit the synthesis of aldosterone, a key driver of difficult-to-treat hypertension.
“So far, we have only had medicines that blocked the effect of aldosterone and did not inhibit its synthesis and spironolactone or eplerenone were the drugs of choice in resistant hypertension. But results indicate that the experimental medicine could be as effective with possibly fewer side effects,” the cardiologist added.
Novel potential
Baxdrostat is a potential first-in-class, highly selective aldosterone synthase inhibitor (ASI) that targets one of the key hormones driving elevated blood pressure and increased cardiovascular and renal risk.
The BaxHTN Phase III trial had three parts. Its primary goal was assessed during a 12-week double-blind, placebo-controlled period. A total of 796 patients were characterised in a 1:1:1 ratio to receive either baxdrostat 2mg or 1mg, or a placebo, once daily.
To assess its long-term safety and efficacy, the drug is also being investigated in clinical trials enrolling more than 20,000 patients globally, as a monotherapy for hypertension and primary aldosteronism, and in combination with dapagliflozin for chronic kidney disease and hypertension, and the prevention of heart failure in patients with hypertension.
But based on the primary results, AstraZeneca, which acquired the therapy following its purchase of CinCor Pharma in 2023, has declared its intent to apply for the drug’s approval in some countries.
Experts, meanwhile, said that even if approved and useful for many, its affordability could be a concern in countries like India.
“I reckon that it will be far more expensive than the currently used generic drugs to treat the condition,” Dr Roy said.
He also hoped that the researchers associated with the drug’s clinical trial had done a head-to-head trial with the current therapies instead of a placebo to better understand the efficacy and safety of the new medicine.
(Edited by Sugita Katyal)
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