New treatment may cure common hormonal cause of high blood pressure

The treatment, known as extended aldosterone synthase inhibition (EASI), involves taking a new class of drugs for 6-12 months to target excess production of the hormone aldosterone, a common cause of high blood pressure. Unlike conventional treatments that control blood pressure, the EASI-treatment appears to reverse its underlying cause, removing the need for lifelong medication. Until now, cure has required surgery to remove an entire adrenal gland.

The study, published in the New England Journal of Medicine, followed 14 people treated at eight centres across the United States. Researchers found that the EASI-treatment led to sustained reversal of excess aldosterone production and partial or complete resolution of high blood pressure for up to two years after treatment ended. 

Hormone levels and blood pressure remained similar to, or lower than, those recorded during their EASI treatment, suggesting that the benefits could persist long after people stop taking the drug. The findings raise the possibility that, for some people, high blood pressure could be cured rather than managed with lifelong medication. 

^{Figure 1: The graphs compare blood pressure and hormone measurements before treatment with those at 6 months, 1 year and 2 years after stopping an extended course of aldosterone synthase inhibition. The large reduction in aldosterone-to-renin ratio is due to a fall in the adrenal gland hormone, aldosterone, and compensatory increase in the kidney hormone, renin. The third row shows apparent safety of the treatment, with only modest increases in blood potassium and creatinine – a marker of kidney function.}

High blood pressure, or hypertension, affects millions of people worldwide. It is estimated that between 5-10 per cent of cases are caused by primary aldosteronism, a condition in which benign nodules in the adrenal glands produce too much aldosterone. This causes the kidneys to retain excess salt, raising blood pressure. 

The scientific basis for EASI-treatment dates back to a 2005 experiment in mice, which showed that deleting the gene responsible for producing aldosterone synthase caused the cells that make aldosterone to disappear. Researchers at Queen Mary predicted that prolonged treatment with an aldosterone synthase inhibitor might have a similar effect in humans, potentially removing the underlying cause of their hypertension.  

The opportunity to investigate this came through the first study of this class of drugs in people with primary aldosteronism, reported last year in the New England Journal of Medicine, in a paper also led by Queen Mary. 

Researchers subsequently examined routine follow-up measurements of people’s blood pressure and hormone levels, comparing them with values recorded before EASI treatment. They found that the main marker of excess aldosterone production remained 99 per cent lower than before treatment, while blood pressure was, on average 25 points lower. Almost a quarter of those who participated had normal blood pressure without taking any other medication. 

Although aldosterone synthase inhibitors have previously been tested in larger studies of people with hypertension, these generally involved shorter treatment periods of 6–12 weeks, with outcomes measured during treatment. In contrast, the new Queen Mary-led study found that the benefits of 6–12 months of treatment persisted for up to two years after treatment had ended.

Morris Brown, lead author and Professor of Endocrine Hypertension at Queen Mary, said: “While duly cautious about our findings because of the pragmatic nature of the study, they were predicted by previous experiments, and longer follow-up may justify a claim that a finite course of medication leads to infinite cure.  

“EASI-treatment is unlikely to be the elixir for most patients with hypertension. But the possibility of tablets achieving a surgical cure has long been a holy grail for this common type of hypertension.” 

Mason Freeman, Professor of Medicine at Harvard Medical School and initiator of the original study while medical director at Cincor, said "This follow up study led by Dr. Brown has generated some extraordinary and unexpected findings. The sustained remission in the biochemical markers of the hyperaldosterone state, combined with much improved blood pressure levels, offers the very exciting possibility that many patients with primary aldosteronism may be able to be treated with a once a day pill, perhaps for a limited period of time, and obtain similar benefits to what we now achieve only after invasive diagnostic testing and major adrenal surgery.”

Building on these findings, the researchers are now leading a larger prospective clinical trial called ELIXIR to investigate whether the EASI treatment can provide a lasting cure for people with primary aldosteronism. The trial will also use molecular imaging of the adrenal glands to investigate whether prolonged treatment causes aldosterone-producing cells to disappear.