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New Medication Shows Promise in Lowering Uncontrolled High Blood Pressure
Researchers presented findings at the American College of Cardiology annual meeting in Chicago on Saturday, indicating that a novel medication may offer hope for individuals with uncontrolled hypertension. This experimental treatment targets resistant high blood pressure, a condition where existing medications are insufficient.
Experimental Drug Lorundrostat Demonstrates Significant Blood Pressure Reduction
A pivotal Phase 2b clinical trial assessed the efficacy of lorundrostat, an investigational drug, in conjunction with standard hypertension therapies. Participants who received lorundrostat alongside two or three established blood pressure medications experienced a notable reduction in systolic blood pressure (the top number in a reading). This decrease was, on average, 8 points greater than that observed in the placebo group. The results of this significant study are slated for publication in The New England Journal of Medicine.
Expert Perspectives on New Hypertension Therapy
“This novel therapeutic approach for hypertension holds considerable promise,” stated Dr. Luke Laffin, the study’s principal investigator and co-director of the Center for Blood Pressure Disorders at the Cleveland Clinic’s Heart, Vascular and Thoracic Institute. He emphasized the challenges in effectively managing blood pressure within the United States.
Data from the Centers for Disease Control and Prevention reveal that approximately half of U.S. adults grapple with hypertension. Alarmingly, fewer than 25% of those diagnosed have their condition adequately managed.
Understanding Hypertension and Its Risks
Hypertension, or high blood pressure, is clinically defined as readings consistently at or above 130/80 mm Hg. Systolic blood pressure between 120 and 129 mm Hg is classified as elevated, while a normal blood pressure reading is 120/80 mm Hg or lower.
Uncontrolled hypertension, defined by Dr. Laffin as blood pressure remaining at 130/80 mm Hg or higher despite medication, elevates the risk of serious cardiovascular events. These include heart attacks, strokes, heart failure, and kidney failure.
Addressing the Unmet Needs in Hypertension Management
According to Dr. Ajay Kirtane, a cardiologist and professor of medicine at Columbia University Vagelos College of Physicians and Surgeons in New York City, approximately 60% to 70% of medicated hypertension patients achieve blood pressure control. This leaves a substantial 30% to 40% of patients requiring alternative treatment strategies. Dr. Kirtane was not directly involved in the lorundrostat research.
Lorundrostat is specifically designed for this patient population. This medication belongs to a class of drugs known as aldosterone synthase inhibitors. It functions by inhibiting the adrenal glands’ production of aldosterone, a hormone crucial in regulating sodium retention. By reducing aldosterone levels, the body retains less salt, consequently lowering blood pressure.
Clinical Trial Design and Participant Demographics
To evaluate lorundrostat’s safety and effectiveness, Dr. Laffin and his team enrolled 285 adults with uncontrolled hypertension, with an average age of 60. A significant proportion of the study participants, 53%, were Black.
Dr. Laffin highlighted the heightened risk of hypertension among Black individuals, citing that approximately 55% of Black adults in the U.S. have high blood pressure, according to the American Heart Association.
Dr. Oscar Cingolani, director of the hypertension program at Johns Hopkins Medicine, emphasized the importance of the diverse patient population in the trial. He noted that “African Americans … tend to be more responsive to this pathway,” making the inclusion of a substantial number of Black participants particularly relevant.
Study Methodology and Blood Pressure Monitoring
All participants were already receiving blood pressure-lowering medications prior to the trial. At the trial’s outset, researchers standardized these medications to a regimen of two or three specific drugs for all participants. After three weeks, participants were randomly assigned to receive either a placebo or one of two dosages of lorundrostat for a 12-week period.
Blood pressure was monitored using 24-hour ambulatory blood pressure monitoring at three intervals: baseline, four weeks after treatment initiation, and at the study’s conclusion at 12 weeks.
Trial Results: Lorundrostat Efficacy
Participants receiving the lower dose of lorundrostat (50 milligrams) in addition to standard medications experienced an average systolic blood pressure reduction of 15.4 points. In contrast, the placebo group, also on standard medications, showed a decrease of 7.4 points. Thus, the net blood pressure decrease attributable to lorundrostat beyond the placebo effect was 8 points.
Increasing the lorundrostat dosage did not yield further improvements in blood pressure reduction.
Experts attributed the observed placebo response to the study environment and increased patient adherence to medication regimens due to heightened medical attention.
Clinical Significance of Blood Pressure Reduction
Dr. Deepak Bhatt, director of the Mount Sinai Fuster Heart Hospital in New York City, explained that an 8-point reduction in systolic blood pressure, for instance, from 170 to 162, could translate to meaningful reductions in the occurrence of heart attacks and strokes in longer-term studies.
Future of Aldosterone Synthase Inhibitors and Lorundrostat Availability
Aldosterone synthase inhibitors represent a relatively new class of medications. Dr. Bhatt noted that several drugs in this category are progressing toward potential FDA approval. Baxdrostat, another aldosterone synthase inhibitor, is currently in Phase 3 clinical trials.
Lorundrostat has successfully navigated Phase 1, 2, and 3 clinical trials, indicating promising results throughout its development. While Phase 3 trial results are pending publication, Dr. Laffin indicated that the drug could potentially become available within 12 to 18 months. Mineralys Therapeutics, the pharmaceutical company sponsoring the trials, funded the research.
Potential Side Effects and Future Research
Trial participants taking lorundrostat exhibited a higher incidence of elevated potassium levels compared to the placebo group. Dr. Bhatt advised that physicians would need to monitor potassium levels in patients prescribed lorundrostat due to the risk of potentially causing abnormal heart rhythms.
Dr. Cingolani advocated for further long-term studies on lorundrostat. He also suggested comparative studies evaluating lorundrostat against spironolactone, an older medication that also targets the aldosterone pathway by blocking its receptor.