Uncontrolled hypertension? A new therapy changes the rules of the game.

Living with uncontrolled hypertension is a challenge millions of people face every day. Despite multiple therapies and lifestyle changes, a significant portion of patients fail to achieve adequate blood pressure. This results in an increased risk of heart attack, stroke, kidney failure, and cardiovascular death. It is against this backdrop that encouraging results from the Phase III BaxHTN study, evaluating the efficacy and safety of baxdrostat, a new investigational drug for difficult-to-treat hypertension, are emerging.

The results of the BaxHTN study

The multicenter, randomized BaxHTN study enrolled 796 patients with uncontrolled or resistant hypertension, meaning patients unable to achieve target blood pressure despite the use of at least two or three antihypertensive medications (including a diuretic). Participants were randomly assigned to receive baxdrostat (1 mg or 2 mg) or placebo, in addition to standard therapy, once daily for 12 weeks. Baxdrostat achieved the study's primary endpoint, a statistically significant and clinically relevant reduction in mean resting systolic blood pressure compared to placebo. The drug was generally well tolerated, with a favorable safety profile even in long-term treatment.

A targeted mechanism of action

Baxdrostat is a highly selective inhibitor of aldosterone synthase (ASI), an enzyme involved in the production of aldosterone, the hormone that regulates sodium and water balance in the body and which, if in excess, can contribute to elevated blood pressure. Several studies indicate that aldosterone dysregulation is a major cause of resistant hypertension. By targeting this mechanism, baxdrostat introduces a completely new therapeutic approach in an area that has seen no significant innovations in the past twenty years.

The experts' opinion

“Many people continue to experience difficulty controlling their blood pressure, even when taking multiple medications. The very promising results from the Phase III BaxHTN study demonstrate that baxdrostat, administered once daily in addition to standard therapy, can significantly reduce systolic blood pressure, offering a potential new therapeutic approach for the control of hypertension, the main risk factor for cardiovascular disease,” said Professor Bryan Williams , Chair of Medicine at University College London and principal investigator of the study.

Extension of the study and public presentation

In addition to the initial 12-week period, the study included a double-blind extension to evaluate the persistence of efficacy: approximately 300 patients treated with baxdrostat 2 mg were re-randomized to continue treatment or receive a placebo for 8 weeks. Again, systolic blood pressure was significantly lower in the treated group compared to the placebo. Long-term safety evaluation at 52 weeks compared to standard treatment is also ongoing. The study results will be officially presented during a late-breaking session at the European Society of Cardiology (ESC) Congress in August 2025 and shared with regulatory authorities globally.

An evolving molecule

Baxdrostat is also currently being tested in other areas: it is being studied as a treatment for primary aldosteronism, alone for hypertension, and in combination with dapagliflozin for the management of chronic kidney disease and the prevention of heart failure in high-risk hypertensive patients.

A global problem still unsolved

The World Health Organization estimates that over 1.3 billion people worldwide suffer from hypertension. Over time, this condition can damage blood vessels and vital organs, increasing the risk of serious health complications. Resistant hypertension is the most severe and persistent form. Despite lifestyle changes and the use of multiple drug therapies, a significant portion of people with hypertension do not reach their desired blood pressure targets. Uncontrolled hypertension persists despite treatment with two or more drugs, while resistant hypertension, a more severe form, remains elevated even after the use of three or more antihypertensive drugs.

The role of aldosterone

One of the main factors contributing to difficult-to-control hypertension is aldosterone, a hormone that contributes to increased blood pressure by promoting sodium and water retention. High aldosterone levels, along with factors such as obesity, excessive salt consumption, and genetic or secondary conditions, are strongly associated with difficult blood pressure control. If not properly treated, the condition significantly increases the risk of heart attack, stroke, and deterioration of kidney function.

A new therapeutic perspective

In this scenario, baxdrostat could represent a turning point, introducing an innovative treatment targeting a specific biological mechanism and offering a concrete solution to those who, until now, have not found effective solutions. Attention is now focused on long-term data and approval by health authorities. For many people with uncontrolled hypertension, this could truly be the breakthrough they have been waiting for years.