Methodological considerations
malignant disease
EVENTS, MALIGNANT DISEASE
The strengths of this multicenter, open-labeled sub-study of 921 patients include a long and nearly complete follow-up period and a large number of events ensured by the comprehensive Danish registries. However, important limitations need to be addressed. First, patients were selected using a list of criteria, including HFrEF patients as well as excluding patients with NYHA-class 4, malignant disease, and an expected lifetime of < 5 years. Although the excluded group of patients may have had a larger number of events, this does not contradict our conclusion. However, the generalizability is limited to NYHA-class 1–3 HFrEF patients without recent malignant disease in a universal healthcare system such as Denmark. Additionally, the majority of the Danish population is Caucasian, thus our results may not be generalizable to non-Caucasian individuals. Secondly, cross-over after the follow-up end of the Northstar trial is a possibility, particularly given the numerous HF hospitalizations across the total follow-up period. However, for patients followed in the PC, we observed no gap in adherence to evidence-based medical treatment nor in survival during the first 5 years after follow-up. Furthermore, the results of this study depend on the quality of data including the discharge diagnosis. In this regard, it is important to note that the discharge diagnosis of HF has a low sensitivity [