A team of West Australian researchers has tested a ground-breaking new treatment for those with high-blood pressure, one of the world’s leading causes of death.
Chair in Clinical Research at the Dobney Hypertension Centre (DHC), Professor Markus Schlaich, from UWA’s Medical School, shared the positive findings from the Phase 3 PRECISION trial of a new drug targeting treatment-resistant hypertension with Perth audiences at a special media conference held on 16 November 2022 at the DHC.
“The trial tested a new drug, aprocitentan, which blocks the effects of endothelin – a very potent constrictor of blood vessels – and after four weeks of treatment, we found a clinically meaningful lowering of both office and 24-hour out-of-office blood pressure in patients with treatment-resistant hypertension,” Professor Schlaich said.
“What we saw is significant blood pressure lowering of around 10 – 15 points, which is quite significant in this difficult to control group of patients.
“Very importantly, this was backed up by what we consider the gold standard of assessing blood pressure, namely 24-hour ambulatory blood pressure monitoring, where a patient wears a blood pressure cuff for a full day and night – which gives us a much better reflection of their true blood pressure during that time.
“And the results were substantial, particularly during night-time. We had a blood pressure reduction of around ten points with this specific measure, and we would estimate that equates to a risk reduction of at least 30 to 35% in these patients. So, it’s big news.”
Significantly, the effects were sustained for 48 weeks and the international trial, which included some 730 participants, also reported no unexpected safety signals, with the main adverse event being oedema (fluid retention), which can usually be managed with additional diuretic therapy.
Professor Schlaich explained that endothelium, a molecule produced by the body, is one of the most potent natural vasoconstrictors, which helps to drive up blood pressure when released.
“[Aprocientan] targets the receptor for this specific molecule – the so-called endothelium A and B receptors. It is a dual endothelial antagonist, and by blocking these receptors, it prevents the molecule from causing vasoconstriction: it keeps it the blood vessel open and widens it,” Professor Schlaich said.
“But it also has several additional mechanisms. For example, endothelium increases aldosterone secretion, another important hormone, and by blocking the receptor, again you get a reduction. [Aprocientan] essentially covers a number of systems in one hit – and that makes it quite unique.
“I believe we get this significant blood pressure lowering effect because the [so-called endothelial] system stands alone, and nobody was taking care of it… The Phase 3 PRECISION study is a significant breakthrough as a promising new therapeutic approach.”
Professor Schlaich has just returned from presenting the findings to the American Heart Association and hopes that the drug will become available in the not-too-distant future, following its upcoming submission to the US Food and Drug Administration.
Hypertension is the biggest single killer world-wide, with an estimated 10 million deaths a year directly attributable to uncontrolled blood pressure.
More than 30% of adult Australians are affected by high blood pressure, and while many are successfully treated with currently available therapies, a significant proportion are categorised as having treatment-resistant hypertension.
The ground-breaking research was made possible with the ongoing support from the RPH Research Foundation, which has a long-standing partnership with the Dobney Hypertension Centre and provides in-house facilities in their research hub at the RPH Campus.
RPH Research Foundation Chair, Professor Lyn Beazley AO, said it was an exciting development.
“We know the significant health impacts of hypertension, and the importance of being able to offer a potential new treatment for those patients who have been treatment-resistant,” Professor Beazley said.
“The results of the Phase 3 trial are very promising and highlight the importance of supporting the brilliant scientific researchers we have here in WA, [and] the RPH Research Foundation is thrilled to have played a role in developing a potential new treatment for this condition.
“As WA’s former Chief Scientist, I am acutely aware of the impact of medical advances, which simply wouldn’t be possible without medical research. I am always in awe of what can be delivered when you invest in people with the passion and purpose to improve health outcomes.”