Benefit of integrated care in patients with atrial fibrillation- a predictive heterogeneous treatment effect analysis of the ALL-IN trial

FUNDING ACKNOWLEDGEMENTS: Type of funding sources: None. INTRODUCTION: Integrated care is effective in reducing all-cause mortality in patients with atrial fibrillation (AF) in primary care. Although this overall effect is undisputed, some individual patients may benefit more than others. The aim of this post-hoc analysis of the cluster-randomized ALL-IN trial, performed in primary care, is to explore heterogeneity of the effect of integrated AF care. METHODS: A model was developed and validated to predict the outcome all-cause mortality using the CHA2DS2-VASc items as predictors. The hazard ratio and absolute risk reduction were plotted as a function of this predicted mortality risk using the ALL-IN data. The interaction between treatment and predicted risk was tested for significance to identify treatment heterogeneity. RESULTS: Among 1,240 AF patients included in the ALL-IN trial (median 77 years (range 65-104), 49.4% female) the model for predicted mortality showed a c-statistic of 0.72 [95% CI 0.66-0.78] with good calibration. The hazard ratio for the intervention across all risk levels ranged from 0.28 to 0.81, yet without a significant interaction effect (p for interaction=0.93). However, the absolute risk reduction of integrated AF care was greatest in patients with the highest predicted risk. CONCLUSION: Independent of the risk of mortality related to comorbidities, all AF patients benefit from integrated care in the primary care setting. Importantly, on an absolute scale, the effect is greatest in patients with a high-risk profile of comorbidities. These results stress the need for integrated AF care, including patients at high-risk of mortality and with multimorbidity. [Figure: see text]