OBJECTIVES: Regulatory agencies have harmonized guidelines defining the requirements for efficacy of chronic heart failure (CHF) interventions in clinical trials. While FDA designates CHF treatments for Priority Review, EMA follows a standard procedure. Such divergence may lead to disparities in data requirements for approval. Consequently, the COA endpoint strategies may differ. We aim at exploring FDA and EMA requirements for CHF endpoint strategy.

METHODS: A search was conducted using Mapi Research Trust’s databases: a) PROINSIGHT®, to review EMA and FDA guidelines on CHF trials and b) PROLABELS®, to capture labels mentioning COAs of EMA- and FDA-approved drugs.

RESULTS: In the 2016 EMA guideline, CHF primary endpoints encompass mortality, time-to first HF hospitalization, and functional capacity measured with the 6-Minute Walk Test (6MWT). Secondary endpoints include improvement of symptoms (New York Heart Association functional class (NYHA Classification)) and quality-of-life (Minnesota Living with Heart Failure Questionnaire (MLHF) or Kansas City Cardiomyopathy Questionnaire (KCCQ)). This is reflected in 8 CHF drugs labels approved by EMA, with the exception of the Patient Global Impression Scale and the NYHA Classification as primary endpoint [Neparvis].

In 2021, in the COA compendium, FDA recommended the qualified KCCQ to assess CHF symptoms and impact on physical limitation. In 2023, FDA released a guideline on CHF detailing mortality as the sole primary endpoint and secondary endpoints include symptoms, exercise capacity, functional capacity, NYHA classification, and activities of daily living (ADL) (e.g., accelerometry data measured using digital health technology (DHT)). This is reflected in 6 FDA CHF-approved drug labels, except for 6MWT and MLHF as primary endpoint [Lanoxin and BiDil, respectively].

CONCLUSIONS: This work highlights a convergence between HF clinical outcomes (mortality and functional capacity assessment) while in its recent guideline, FDA emphasizes on quality-of-life assessment, as well as the importance of ADL measurement, and supports the use of DHT, which is noteworthy.