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24th November 2022
Use of baxdrostat in patients with treatment-resistant hypertension, concurrently taking three other anti-hypertensives, led to significant reductions in systolic blood pressure compared to placebo according to the findings of a trial by UK and US researchers.
Hypertension is the leading preventable cause of premature death worldwide with one analysis of 90 countries estimated that globally, in 2010, 31.1% of the world’s adults had hypertension and which equated to 1.39 billion people. Despite the availability of a range of effective anti-hypertensive therapies, treatment-resistant hypertension, defined as above-goal elevated blood pressure in a patient despite the concurrent use of 3 antihypertensive drug classes, can be as high as 10.3%. One therapeutic target in hypertension is aldosterone synthase and a new class of drugs, the aldosterone synthase inhibitors, are currently under development. One such agent is baxdrostat and which has been shown in preclinical studies to completely suppress aldosterone production in humans without affecting cortisol production. Nevertheless, whether reducing aldosterone would also lower blood pressure was unclear and the subject of the current study.
Researchers focused on patients with treatment-resistant hypertension with a mean blood pressure of at least 130/80 mmHg, despite the use of three different anti-hypertensives. Participants were then randomised equally to 0.5, 1 or 2 mg of baxdrostat or matching placebo and were assessed for a period of 12 weeks. The primary efficacy endpoint was the change in the mean seated systolic blood pressure from baseline to the end of the study period. The change in diastolic pressure was then set as the secondary outcome measure.
Baxdrostat and changes in systolic blood pressure
A total of 248 patients with a mean age of 62.3 (55.8% male) were included and randomised to either placebo, 0.5, 1 and 2 mg of baxdrostat. The mean baseline systolic blood pressure ranged from 147.7 to 148.9 mmHg and the mean diastolic from 87.6 to 88.2 mmHg.
The change in systolic blood pressure at 12 weeks was significantly greater than placebo for the 2 mg dose (-20.3) and the mean difference compared to placebo was significant (p < 0.001). Similarly, the 1 mg dose achieved -17.5 reduction in systolic pressure and again the mean difference compared to placebo was significant (p = 0.003). There was no significant difference for the 0.5 mg dose.
The highest reduction in diastolic pressure occurred with the 2 mg dose (-14.3) and the 1 mg dose (-11.8) although no statistical significance data were reported.
The authors that there were reported no serious adverse events attributable to baxdrostat, and no instances of adrenocortical insufficiency.
They concluded that in patients with treatment-resistant hypertension, baxdrostat provided a dose-related reduction in blood pressure.
Freeman MW et al. Phase 2 Trial of Baxdrostat for Treatment-Resistant Hypertension. N Eng J Med 2022