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Drug Developed to Treat Uncontrolled Hypertension Significantly Lowers Blood Pressure

Findings from a clinical trial led by a Cleveland Clinic cardiologist showed that lorundrostat – a new type of blood pressure medication — safely decreased blood pressure in patients with uncontrolled hypertension.

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Lorundrostat was developed to address abnormally elevated aldosterone, a hormone your adrenal glands release that regulates blood pressure by managing the levels of sodium and potassium in your blood. Image for illustration purposes
Lorundrostat was developed to address abnormally elevated aldosterone, a hormone your adrenal glands release that regulates blood pressure by managing the levels of sodium and potassium in your blood. Image for illustration purposes

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Findings were presented during a late breaking science session at the American Heart Association’s annual Hypertension Scientific Sessions in Boston and simultaneously published in the Journal of the American Medical Association. 

High blood pressure, also called hypertension, is when the force of blood pushing against your artery walls is consistently too high. This damages your arteries over time and can lead to serious complications like heart attack or stroke. Uncontrolled or resistant hypertension is when your blood pressure remains high or unmanaged, despite taking medications. People with hard-to-treat, resistant hypertension have an even higher risk of stroke, kidney disease and heart failure than those whose high blood pressure is regulated.

Lorundrostat was developed to address abnormally elevated aldosterone, a hormone your adrenal glands release that regulates blood pressure by managing the levels of sodium and potassium in your blood. Aldosterone synthase inhibitors are a novel class of blood pressure-lowering medication that decrease the body’s production of aldosterone. Medicines currently available for patients block the receptor for aldosterone, but aldosterone can still be circulating and have a negative impact on patients. Up to 25 percent of all people with hypertension exhibit abnormal aldosterone levels.

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In the Target-HTN Phase 2 randomized clinical trial, 200 patients were given a placebo or one of five different doses of lorundrostat, ranging from 12.5mg to 100mg a day. Researchers found patients who had taken the drug had lower blood pressure, particularly at the higher dosages. Those taking 50mg daily dose of lorundrostat saw a decrease of 10 blood pressure points when compared to placebo. The amount of blood pressure lowering was even better among individuals with obesity.

“We know that only a third of people with high blood pressure in the United States have it under control and we know obesity is a major factor increasing blood pressure,” said the study’s lead author Luke Laffin, M.D., co-director of the Center for Blood Pressure Disorders in the Heart Vascular & Thoracic Institute at Cleveland Clinic. “New strategies and new safe, effective medications are needed to help this patient population. While further studies of this drug are needed, these results are encouraging, particularly among patients with obesity-associated hypertension.”

“These findings are important because no new classes of blood pressure lowering-drugs have been introduced for many years, said the study’s senior author , Steven E. Nissen, M.D., Chief Academic Officer of the Heart, Vascular & Thoracic Institute at Cleveland Clinic. “Blood pressure is difficult to control in some patients particularly those with obesity and diabetes, so new options will be valuable.”

Additional trials are planned to further study this medication paired with standard treatments.

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The study was funded by Mineralys Therapeutics, developer of lorundrostat.

Dr. Laffin has served on steering committees for Mineralys Therapeutics, however, he did not receive any compensation.

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