Short Drug Course May Cure Hormone-Driven High Blood Pressure, Small Study Suggests

A course of tablets lasting six to twelve months may be enough to switch off a common hormonal cause of high blood pressure, and the effect appears to hold for as long as two years after the pills are stopped. That is the finding of a study led by Queen Mary University of London and published in the New England Journal of Medicine.

The approach is called extended aldosterone synthase inhibition, or EASI. It uses a new class of drugs that block production of aldosterone, a hormone that makes the kidneys retain salt and so pushes blood pressure up. Conventional treatment controls the pressure while the patient keeps taking medication. Until now, the only cure for this form of hypertension has been surgery to remove an entire adrenal gland.

The condition behind it is primary aldosteronism, in which benign nodules in the adrenal glands produce too much aldosterone. It is estimated to account for 5 to 10 per cent of high blood pressure cases, in a disease that affects millions of people worldwide.

The idea has a long lineage. A 2005 experiment in mice showed that deleting the gene for aldosterone synthase made the aldosterone-producing cells disappear. Researchers at Queen Mary predicted that prolonged treatment with an inhibitor of the enzyme might do something similar in people, removing the root of the hypertension. The chance to test that came from the first study of this drug class in people with primary aldosteronism, reported last year in the same journal, also led by Queen Mary.

In the new work, the team looked at routine follow-up measurements of blood pressure and hormone levels in 14 people treated at eight centres across the United States, and compared them with values from before treatment. The main marker of excess aldosterone production stayed 99 per cent lower than before treatment. Blood pressure was on average 25 points lower. Almost a quarter of participants had normal blood pressure without taking any other medication. Hormone and blood pressure readings stayed similar to, or better than, those recorded while patients were on the drug.

The duration is what sets the work apart. Aldosterone synthase inhibitors have been tested before in larger groups of people with hypertension, but those trials generally ran for 6 to 12 weeks and measured outcomes during treatment. Here, the benefit of 6 to 12 months of treatment outlasted the treatment itself.

Morris Brown, lead author and Professor of Endocrine Hypertension at Queen Mary, urged caution because of the pragmatic nature of the study, though he noted the results were predicted by earlier experiments. He said longer follow-up might justify claiming that a finite course of medication leads to an infinite cure. He also said EASI is unlikely to be the elixir for most people with hypertension, but that tablets achieving a surgical cure have long been a holy grail for this type.

Mason Freeman, Professor of Medicine at Harvard Medical School, who initiated the original study while medical director at Cincor, called the findings extraordinary and unexpected. He said they raise the prospect that many patients could be treated with a once-a-day pill, perhaps for a limited time, and gain benefits now achieved only after invasive diagnostic testing and major adrenal surgery.

The researchers are now leading a larger prospective trial, ELIXIR, to test whether EASI can give a lasting cure in primary aldosteronism. It will also use molecular imaging of the adrenal glands to check whether prolonged treatment really makes the aldosterone-producing cells disappear.