title: Geographic differences in heart failure trials.
abstract: Randomized controlled trials (RCTs) are essential to develop advances in heart failure (HF). The need for increasing numbers of patients (without substantial cost increase) and generalization of results led to the disappearance of international boundaries in large RCTs. The significant geographic differences in patients' characteristics, outcomes, and, most importantly, treatment effect observed in HF trials have recently been highlighted. Whether the observed regional discrepancies in HF trials are due to trial-specific issues, patient heterogeneity, structural differences in countries, or a complex interaction between factors are the questions we propose to debate in this review. To do so, we will analyse and review data from HF trials conducted in different world regions, from heart failure with preserved ejection fraction (HF-PEF), heart failure with reduced ejection fraction (HF-REF), and acute heart failure (AHF). Finally, we will suggest objective and actionable measures in order to mitigate regional discrepancies in future trials, particularly in HF-PEF where prognostic modifying treatments are urgently needed and in which trials are more prone to selection bias, due to a larger patient heterogeneity.
authors.affiliation: INSERM, Centre d'Investigations Cliniques Plurithématique 1433, Université de Lorraine, CHRU de Nancy and F-CRIN INI-CRCT, Nancy, France.|Department of Physiology and Cardiothoracic Surgery, Cardiovascular Research and Development Unit, Faculty of Medicine, University of Porto, Porto, Portugal.
authors.forename: João Pedro
authors.initials: JP
authors.lastname: Ferreira
authors.affiliation: INSERM, Centre d'Investigations Cliniques Plurithématique 1433, Université de Lorraine, CHRU de Nancy and F-CRIN INI-CRCT, Nancy, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Girerd
authors.affiliation: INSERM, Centre d'Investigations Cliniques Plurithématique 1433, Université de Lorraine, CHRU de Nancy and F-CRIN INI-CRCT, Nancy, France.
authors.forename: Patrick
authors.initials: P
authors.lastname: Rossignol
authors.affiliation: INSERM, Centre d'Investigations Cliniques Plurithématique 1433, Université de Lorraine, CHRU de Nancy and F-CRIN INI-CRCT, Nancy, France.
authors.forename: Faiez
authors.initials: F
authors.lastname: Zannad
mesh_terms: D017281:Cost of Illness; D019468:Disease Management; D014943:Global Health; D006333:Heart Failure / Q000191:economics / Q000453:epidemiology / Q000628:therapy; D006801:Humans; D009017:Morbidity / Q000639:trends; D016032:Randomized Controlled Trials as Topic
keywords: Geographic differences; Heart failure; Outcomes; Randomized controlled trials; Treatment effect