Quality of inclusion criteria in the registered clinical trials of heart failure with preserved ejection fraction: Is it time for a change?

Abstract

BackgroundNo uniform diagnostic criteria have been developed for heart failure with preserved ejection fraction (HFpEF), resulting in huge discrepancies in the patient recruitments of HFpEF trials. This study aims to assess the quality of inclusion criteria in HFpEF trials. MethodsWe systematically searched the International Clinical Trials Registry Platform for HFpEF trials and extracted the basic characteristics and inclusion criteria. We then scored and compared the quality of inclusion criteria using an adapted 5-point scoring system of ejection fraction (EF), symptoms, signs, natriuretic peptides and other tests. ResultsA total of 121 trials and 19,494 patients were finally included for statistical analyses. More than half (67/121, 55.4%) of the trials employed 50% as the cut-off value for diagnosing HFpEF. Symptoms (102/121, 84.3%) are mostly provided by trial registrars, followed by natriuretic peptides (46/121, 38.0%) and signs (32/121, 26.4%). Average total scores of inclusion criteria wavily increased from 2.00 in 2002 to 3.00 in 2016 (P=0.04). Interventional trials were not significantly different from observational trials (3.00±1.18 vs. 2.75±1.53, P=0.45), but ongoing trials were higher in total score than completed trials (3.28±1.24 vs. 2.72±1.17, P=0.01). Published trials were not significantly different from the unpublished trials at registration (2.76±1.13 vs. 2.69±1.20, P=0.82), but their total scores significantly increased to 3.48±0.96 at publication (P<0.01). ConclusionsThe qualities of inclusion criteria are heterogeneous and significantly improved with time in registered HFpEF clinical trials. EF, symptoms and signs should be specified at trial registration to make a more reliable diagnosis and to recruit a more homogenous population.