Statistical Analysis
atrial fibrillation
ATRIAL FIBRILLATION, SECONDARY, TYPE 2 DIABETES, POLAND
The Beta3-LVH trial tested the hypothesis that, compared with placebo, mirabegron as an add-on to standard treatment improves at least 1 of the 2 primary end points over 12 months. The Hochberg method was used to adjust for end-point multiplicity; that is, efficacy was claimed for both primary end points if both Sample size calculation was based on the E/e′ ratio, with the aim to detect a difference of 1.2 between the 2 treatment groups. This roughly corresponds to 5 points on the Short Form-36 physical functional scale, a patient-relevant difference.Analyses of both primary and secondary end points were identically structured. Mean changes from baseline were analyzed using a repeated-measures linear mixed model without the intercept containing the fixed, categorical effects of visit (baseline, 6 months, or 12 months), treatment (active or placebo), treatment-by-visit interaction, atrial fibrillation (yes or no), type 2 diabetes (yes or no), and a patient-specific visit random effect (3-dimensional normal with a general unstructured variance covariance matrix). The model implicitly used the estimated covariance matrix to deal with missed visits. Assuming that missing end points are missing at random, the model can deal with patients with incomplete end-point data provided that at least 1 valid measurement is documented. Given randomization at baseline, the treatment by baseline interaction was not included in the model. This indirectly adjusted for possible random chance fluctuation at baseline and generally increased the power.The per-protocol set included all patients from the full analysis set without major violations of the study protocol. The population in the safety analysis set was defined by all randomized patients belonging to the full analysis set who received at least 1 dose of study medication.Exploratory subgroup analyses for the 2 primary end points were performed with baseline characteristics, including sex, β-blocker use in standard treatment, type 2 diabetes, atrial fibrillation at registration, age older than 65 years, BMI greater than 30 at baseline, and region (Poland, Germany, or other countries).We used χ