Heart failure (HF) treatment relies heavily on pharmacotherapy, particularly combining multiple therapies as recommended by clinical guidelines. However, non-adherence to prescribed regimens remains a significant challenge, contributing to increased hospitalizations and poorer patient outcomes. This study introduces a novel methodological pipeline that integrates Latent Markov Models (LMM) with dynamic adherence modeling to evaluate adherence behaviors and their impact on HF rehospitalization. Using administrative healthcare data from Lombardy, Italy, we analyzed 6,818 patients hospitalized for HF between July and December 2020. Adherence was assessed monthly over a six-month observation period, and adherence profiles were linked to clinical outcomes using Cox regression. Seven latent behavioral profiles were identified, reflecting varying levels and trajectories of adherence. The findings revealed that higher adherence levels significantly reduced the risk of rehospitalization. Patients with consistently high adherence exhibited a 56% lower risk of HF rehospitalization compared to those with low adherence. Importantly, improving adherence during the observation period was associated with better survival probabilities, highlighting the potential benefits of timely interventions. Additionally, adherence behaviors were influenced by factors such as age, comorbidity burden, and hospitalization during the observation period. This study underscores the importance of dynamic and personalized strategies to monitor and enhance adherence to polytherapy. By linking adherence patterns to clinical outcomes, the proposed approach offers actionable insights for improving patient management and reducing the burden of HF on healthcare systems.

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