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Few agonists of the third isotype of beta-adrenergic receptors, the β3-adrenoreceptor, are currently used clinically, and new agonists are under development for the treatment of overactive bladder disease. As the receptor is expressed in human cardiac and vascular tissues, it is important to understand their beneficial (or adverse) effect(s) on these targets. We discuss the most recent results of clinical trials testing the benefit and safety of β3-adrenoreceptor activation on cardiovascular outcomes in light of current knowledge on the receptor biology, genetic polymorphisms, and agonist pharmacology. While evidence from small clinical trials is limited so far, the β3-agonist, mirabegron seems to be safe in patients at high cardiovascular risk but produces benefits on selected cardiovascular outcomes only at higher than standard doses. Activation of cardiovascular β3-adrenoreceptors deserves to be tested with more potent agonists, such as vibegron.

Clinical pharmacology of β-3 adrenergic receptor agonists for cardiovascular diseases