Underrepresentation and exclusion of patients with cardiovascular disease in intensive care randomized controlled trials.

Abstract

Aims: The complexity of the contemporary cardiac intensive care unit has increased due to a growing prevalence of multisystem, non-cardiac illnesses. Despite this increase, patients with cardiovascular disease (CVD) are often under-represented in intensive care randomized controlled trials (RCT). We sought to quantify the representation of patients with CVD comorbidities in intensive care RCTs.

Methods and results: We searched MEDLINE for trials published from 2007 to 2019 with the five highest journal impact factors in the disciplines of critical care medicine, general internal medicine, and cardiovascular disease. Prospective RCTs in the adult (age ≥18 years), intensive care setting with ≥50 individuals were included. Study characteristics, proportion of patients with CVD and cardiovascular exclusion criteria were extracted independently by two reviewers. We used multivariable logistic regression analysis to identify independent predictors of cardiovascular exclusion and representation. A total of 412 eligible RCTs were identified for analysis, 132 (32.0%) of which included specific CVD-related exclusion criteria with a history of heart failure (29.5%) and of ischaemic heart disease (26.5%) being the most common exclusions. Exclusions were more likely in multicentre trials and varied substantially across study intervention categories. Representation of CVD, reflected by the reporting of any CVD history, was noted in 150 (36.4%) RCTs. Of those reporting, the prevalence of any CVD, ischaemic heart disease and heart failure were 15.7%, 13.2%, and 10.2%, respectively.

Conclusion: Those with comorbid CVD are both frequently excluded and underrepresented in intensive care RCTs, limiting the application of RCTs to this physiologically complex patient population.