Efficacy and Safety of the β3-Adrenergic Agonist Mirabegron in Patients with Heart Failure: An Updated Systematic Review and Meta-Analysis

Heart failure (HF) remains a leading cause of global mortality. β3-adrenergic receptors are upregulated in HF and their activation has demonstrated cardioprotective effects in preclinical studies. This systematic review and meta-analysis evaluated the efficacy and safety of the β3-adrenergic agonist mirabegron in HF patients. Five randomized controlled trials including 538 participants were analyzed. Mirabegron showed no definitive evidence of improved physical capacity, quality of life, left ventricular ejection fraction (pooled mean difference of change from baseline = +0.51%, 95% CI: -4.56 to 5.57) or NT-proBNP (pooled mean difference of change from baseline = +5.42 pg/mL, 95% CI: -292.15 to 302.98). However, isolated benefits in cardiac index and pulmonary vascular resistance were noted in severe HF. Mirabegron did not demonstrate definitive evidence of safety in HF patients, with a 4% higher odds of serious adverse events compared to placebo (OR = 1.04, 95% CI: 0.63 to 1.72), and a 4:0 imbalance in deaths with mirabegron compared to placebo. No statistically significant changes were seen in systolic or diastolic blood pressure, heart rate, QT interval, or urinary adverse events. The GRADE certainty of evidence for left ventricular ejection fraction, systolic blood pressure, and urinary adverse events was rated low due to serious imprecision and high risk of publication bias. Mirabegron did not demonstrate definitive evidence of improved physical capacity, quality of life, or cardiac function in HF, although isolated benefits were noted. Mirabegron's safety profile in HF patients remains uncertain. Larger, long-term trials targeting patients with severe HF are warranted.