Multi-state models for survival analysis in cardiology: an alternative to composite endpoints

To the Editor, The main objective of longitudinal studies conducted in cardiology is often time-to-adverse events (AE) to identify possible risk factors or the efficacy of treatment. Traditionally, composite endpoints have been used, often major adverse cardiovascular events (MACE) in their different versions. Their great advantage is to increase the statistical power of the studies and simplify analysis. However, they complicate the interpretation of results1 and have other limitations like giving the same weight to every event or using the information of the index event only. Therefore, over the last few years, concern has been growing on whether these methods should be updated.2 The problem with data analysis in longitudinal studies with several AE of interest can be approached using multi-state models in a natural way since they create models with a complex structure of relations during the appearance of different events and account for all the data available from every patient. Also, they provide information on time expected and probability of appearance of each AE, and establish their interdependence with risk factors or with the characteristics of treatment.3 The main advantages of multi-state models compared to other models commonly used are shown on table 1. Table 1. Comparison between the most commonly...