Discussion
obesity, heart disease, Heart Failure I and II, heart failure, hypertension
OBESITY, HEART DISEASE, DISEASE, OVERACTIVE BLADDER, TYPE 2 DIABETES, ATRIAL FIBRILLATION, HEART FAILURE, HYPERTENSION, INSULIN SENSITIVITY
Changes in the primary end points of LVMI or E/e′ over 1 year of treatment did not differ between the 2 Beta3-LVH groups treated with mirabegron or placebo. The current therapeutic mirabegron dosage (50 mg/d) did not cause harm in a selected patient population at risk of developing or worsening HF.Thus far, very few clinical trials have tested the effect of mirabegron on cardiovascular outcomes. Two pilot studies (Beta 3 Agonist Treatment in Heart Failure I and II [BEAT-HF I and BEAT-HF II]) evaluated the effect of high dosages of mirabegron (300 mg/d) on LV function in patients with heart failure with reduced ejection fraction (HFrEF).To our knowledge, Beta3-LVH is the first trial to test the longer-term effects of mirabegron (over 12 months) in a patient population with pre-HF structural heart disease (stage B) at risk of developing (or worsening) HF,Compared with previous literature on similar patients, our study population had lower LVMI and E/e′ at baseline, which left limited room for treatment-specific improvement. Despite our selection of primarily patients with hypertension (>90%), LVMI (determined with cardiac MRI analysis in the core laboratory) was relatively low and did not progress substantially in the placebo group. This finding is consistent with more recent literature on hypertensionThe mirabegron dosage used here (50 mg/d) was shown previously to produce white adipocyte “beiging” and improvements in metabolic parameters, including insulin sensitivity in a patient population with obesity that was comparable to that of Beta3-LVH.To our knowledge, Beta3-LVH is the first placebo-controlled randomized clinical trial to assess AE incidence in a patient population with a more severe cardiovascular risk profile (ie, with hypertension, obesity, and structural heart disease and type 2 diabetes or atrial fibrillation) than in previous phase 3 or 4 trials of mirabegron for overactive bladder disease.