The analysis of clinical pathways from event logs provides new insights about care processes. In this paper, we propose a new methodology to automatically perform simulation analysis of patients’ clinical pathways based on a national hospital database. Process mining is used to build highly representative causal nets, which are then converted to state charts in order to be executed. A joint multi-agent discrete-event simulation approach is used to implement models. A practical case study on patients having cardiovascular diseases and eligible to receive an implantable defibrillator is provided. A design of experiments has been proposed to study the impact of medical decisions, such as implanting or not a defibrillator, on the relapse rate, the death rate and the cost. This approach has proven to be an innovative way to extract knowledge from an existing hospital database through simulation, allowing the design and test of new scenarios.