Mirabegron for Cardiac Disease: A New Therapeutic Frontier

Abstract

Mirabegron, a selective β3-adrenergic receptor agonist approved for overactive bladder, is being investigated for its cardiovascular applications, particularly in heart failure (HF) and left ventricular hypertrophy. This review explores the mechanistic rationale, safety profile, and emerging clinical data supporting β3-adrenergic stimulation as a novel therapeutic strategy. Unlike β1-blockers, mirabegron activates nitric oxide-dependent pathways that confer vasodilatory, antifibrotic, and autonomic regulatory benefits, particularly relevant in HF with preserved ejection fraction. However, its use raises safety concerns, including modest increases in blood pressure, heart rate, and QTc interval, especially in high-risk cardiac populations. Early clinical trials have shown improvements in hemodynamic parameters such as cardiac index and pulmonary vascular resistance, with a neutral or favorable impact on symptoms and ventricular function. Nevertheless, long-term safety, optimal patient selection, and potential for combination therapy with established HF treatments remain unresolved. Future research must prioritize identifying biomarkers predictive of response, evaluating synergy with current therapies, and determining the durability of benefits. Mirabegron represents a promising, mechanistically distinct approach to neurohormonal modulation in HF, with the potential to address gaps unmet by conventional therapies.

Keywords: autonomic modulation; baroreflex sensitivity; cardiovascular safety; heart failure; heart failure with preserved ejection fraction; mirabegron; neurohormonal regulation; nitric oxide signaling; sympathetic nervous system; β3-adrenergic receptor agonist.