Finite Course of Aldosterone-Blocking Pill May Cure Common Hormonal High Blood Pressure

Fourteen people at eight centers across the United States took a new kind of pill for six to twelve months, then stopped. Researchers at Queen Mary University of London have now reported what happened next: for up to two years afterward, the hormonal driver of their high blood pressure stayed suppressed. The findings appear 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 the enzyme the body needs to make aldosterone, a hormone that tells the kidneys to hold on to salt. In primary aldosteronism, benign nodules in the adrenal glands produce too much of it, and blood pressure rises. The condition is estimated to account for between 5% and 10% of all high blood pressure cases. Until now, a cure has meant surgery to remove an entire adrenal gland, while everyone else has relied on medication to control the numbers.

The idea has a long lineage. In 2005, an experiment in mice showed that deleting the gene for aldosterone synthase caused the aldosterone-making cells to disappear. The Queen Mary team reasoned that a long enough course of an inhibitor might do something similar in people, removing the cause rather than masking the effect. Their chance to test it came from the first study of this drug class in people with primary aldosteronism, reported last year in the same journal and also led by Queen Mary.

For the new analysis, the researchers looked at routine follow-up measurements of blood pressure and hormone levels and compared them with values recorded before EASI treatment. The main marker of excess aldosterone production remained 99% 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 levels and blood pressure were similar to, or lower than, those seen during the treatment itself, which suggests the benefit may outlast the drug.

The duration is what sets this apart. Aldosterone synthase inhibitors have been tested before in larger groups of people with hypertension, but those studies generally ran for 6 to 12 weeks and measured results while patients were still on the drug. This one followed people after the treatment ended.

Morris Brown, the lead author and professor of endocrine hypertension at Queen Mary, was careful about what the study can carry. Because the study was pragmatic in design, he said, he is duly cautious, though the results were predicted by earlier experiments, and longer follow-up may justify saying that a finite course of medication leads to an infinite cure. He added that EASI is unlikely to be an elixir for most people with hypertension, but that tablets achieving a surgical cure has long been a holy grail for this type.

Mason Freeman, a professor of medicine at Harvard Medical School who initiated the original study while medical director at Cincor, called the results extraordinary and unexpected. He pointed to the sustained remission in the biochemical markers together with much improved blood pressure, and said many patients might one day be treated with a once-a-day pill, perhaps for a limited time. That would deliver benefits now achieved only after invasive diagnostic testing and major adrenal surgery.

The next step is a larger prospective clinical trial called ELIXIR, which the researchers are now leading. It will test whether EASI can provide a lasting cure for people with primary aldosteronism, and it will use molecular imaging of the adrenal glands to see whether prolonged treatment really does make the aldosterone-producing cells disappear.