The addition of AZD5462, an oral once-daily relaxin family peptide receptor 1 agonist, was well tolerated among individuals with well-treated chronic heart failure (HF), based on findings from LUMINARA presented at ESC Congress 2026 and simultaneously published in Circulation. In addition, researchers observed encouraging effects on cardiovascular hemodynamic measures across a wide range of left ventricular ejection fraction (LVEF).

The international, multicenter trial divided 375 patients into two cohorts based on LVEF (Cohort A: ≤35%; and Cohort B: 41% to 55%) and randomized them to one of three doses of AZD5462 (20 mg, 80 mg, or 360 mg) or placebo. Primary endpoints were changes in end-systolic volume index (cohort A) and systemic vascular resistance index (cohort B) after 24 weeks.

Overall results found AZD5462 to be well tolerated compared with placebo. In cohort A, AZD5462 had the most beneficial effects on cardiac function at the lowest dose, decreasing the end systolic volume index by 5.4 mL/m2 from baseline. In cohort B, patients across all AZD5462 dose groups experienced significant placebo-adjusted reductions in systemic vascular resistance index.

Researchers noted that the incidence of adverse events was low with no evidence for excess of adverse events among those receiving AZD5462. Mild lowering of blood pressure was noted, but the incidence of significant hypotension was no different in those treated with AZD5462 compared with placebo, they said.

“Target engagement was demonstrated in both cohorts, with signs of improved cardiac function at the lowest AZD5462 dose when given on top of standard-care therapies,” said James L. Januzzi, MD, FACC, who presented the findings. “Larger randomized trials with AZD5462 are now warranted, focused on outcomes.”

In a related editorial comment, Andrew P. Ambrosy, MD, MPH, and Adrian F. Hernandez, MD, MHS, called LUMINARA “informative in many regards,” noting that beyond the primary endpoint or any single p-value, the findings “[establish] biological plausibility in clinically relevant terms, as well as [frame] opportunities and challenges that clarify the path toward future clinical utility of a study drug.”

Visit ACC’s ESC Congress 2026 coverage page to explore the latest science and key takeaways shaping cardiovascular care.

Clinical Topics: Cardiovascular Care Team, Heart Failure and Cardiomyopathies, Acute Heart Failure

Keywords: ESC Congress, ESC26, Heart Failure, Relaxin, Receptors, Peptide, Drug Therapy