ORLANDO, Fla. — First-in-man results suggest that patients with chronic heart failure (HF) who received mirabegron, a beta 3-adrenoceptor agonist, failed to demonstrate improvements in left ventricular ejection fraction (LVEF) compared with patients who received placebo.
“The exploratory analysis indicated an increase in left ventricular ejection fraction in patients with more severe heart failure at baseline [given mirabegron], but not in patients with ejection fraction [≥]40[%],” said study investigator Henning Bundgaard, DMSc during a press conference at the American Heart Association Scientific Sessions.
In the single center, double blind, placebo-controlled randomized BEAT-HF trial, Dr Bundgaard, of the National University Hospital, Rigshospitalet, Copenhagen, and colleagues randomly assigned 70 patients with chronic HF to either mirabegron (Astellas Pharma, Tokyo, Japan) daily (n=35) or placebo (n=35) for 6 months. Currently, mirabegron has received approvals from the United States Food and Drug Administration and European Medicines Agency for treatment of overactive bladder.
Patients who received mirabegron were given an initial dose of 25 mg twice daily, and if tolerated, the dose was increased at 1-week intervals until a target dose of 300 mg, or the highest-tolerated dose, was achieved.
The primary end point was computed tomography assessed change in left ventricular ejection fraction (LVEF). Secondary end point analysis assessed volumetric parameters, physical capacity, laboratory measurements, and electrocardiogram measurements.
Baseline characteristics were similar between groups, with the exception of age (placebo, 56 ± 12 years vs mirabegron, 62 ± 12 years; P=.05).
According to results, all 61 patients who completed the study were compliant, as assessed by pill count, and 94% of the patients reached the target dose.
At 6 months, there was no significant between-group differences in the primary end point (mean difference, 0.4%; P=.82) or any of the secondary end points. Similarly, there were no differences in any of the adverse events measured, including sudden death, chest pain, and serious adverse events.
In an exploratory analysis, patients with a baseline LVEF <40% who were given mirabegron did experience a significant increase in LVEF compared with those given placebo (mean difference, 5.5%; P<.03). However, this association was not observed in patients with an LVEF ≥40% (mean difference, -2%; P=.4).
“The beneficial effect of the beta 3-adrenoceptor agonist only in severe heart failure is in agreement with the mechanistic foundation of our study,” Dr Bundgaard said. “An additional study on effects of beta 3-adrenoceptor agonists in patients with severe heart failure is needed for the design of a phase 3 trial.”
Disclosures: Dr Bundgaard serves on the speakers’ bureau for Amgen, AstraZeneca, Merck Sharp & Dohme, Pfizer, and Sanofi-Aventis.
Bundgaard H. LBCT 04. Novel Therapies for Common Problems. The First-In-Man Randomized Trial of a ß3-Adrenoceptor Agonist in Chronic Heart Failure: BEAT-HF. Presented at: American Heart Association Scientific Sessions; November 7-11, 2015; Orlando, FL.