The investigational drug lorundrostat led to a significant reduction in systolic blood pressure (SBP) at 12 weeks compared to placebo in patients with uncontrolled hypertension, according to a Late-Breaking Clinical Trial presented at ACC.25 in Chicago.

The phase 2b, double-blind trial, only the second to study the effects of the drug on SBP, randomized 285 patients (average age 60 years, 40% women, 53% Black) across 103 sites in the U.S. to one of three groups following a three-week period of standard BP-lowering medications: placebo, 50 mg daily lorundrostat, or 50 mg daily lorundrostat with the potential to increase to 100 mg daily if BP remained uncontrolled at four weeks. Among those in the third group, the dose was increased in 20% of patients. Lorundrostat is an aldosterone synthase inhibitor, a novel class of BP-lowering medication.

Patients were eligible if they had high BP despite taking two to five BP-lowering medications. While investigators had a special focus on enrolling Black patients, who are often underrepresented in antihypertensive drug trials, no differences in treatment effect were seen across racial subgroups.

At four and 12 weeks, patients underwent 24-hour ambulatory BP monitoring. At four weeks, 42% of those in the treatment groups already had their SBP under control compared to 19% in the placebo group.

For the primary endpoint of average mean ambulatory SBP at 12 weeks, a greater reduction was seen in both treatment groups compared to placebo: by 15.4 mm Hg in the 50 mg lorundrostat group, 13.9 mm Hg in the 50-100 mg lorundrostat group and 7.4 mm Hg in the placebo group.

Similar patterns were seen in the secondary endpoints, including change in SBP as measured in a medical office at four and 12 weeks. Side effects were comparable to similar drugs, with some patients seeing an increase in potassium and a decrease in glomerular filtration rate.

"It was overall a well-tolerated drug," said the study's first author, Luke Laffin, MD, FACC. "More studies are needed; however, this drug could be another tool in our armamentarium to reduce blood pressure and, ultimately, reduce the risk from uncontrolled hypertension in terms of outcomes like strokes, heart attacks and heart failure."

Clinical Topics: Prevention, Hypertension

Keywords: ACC Annual Scientific Session, ACC25, Hypertension