People with CKD in cardiovascular trials: a neglected population? A systematic review and evidence map

Abstract Background People with chronic kidney disease (CKD) have a markedly higher risk for cardiovascular disease. Systematic underrepresentation of people with CKD in cardiovascular randomised controlled trials (RCTs) limits evidence to guide cardiovascular risk management (CVRM). Purpose In this systematic review we aimed to identify evidence gaps regarding CVRM medication for people with CKD and evaluated the prevalence of exclusion of people with CKD from cardiovascular RCTs. Method We searched Clinicaltrials.gov through the Cochrane Central Register of Controlled Trials from inception until October 2021. Eligible studies were randomised controlled trials (RCTs) that investigate the efficacy of guideline-recommended CVRM medications on (cardiovascular) mortality, cardiovascular morbidity, and end-stage kidney disease in adults with a history of cardiovascular disease or one or more major risk factors for cardiovascular disease. Two reviewers independently determined the eligibility of references and extracted data. Outcomes were an overview of studies that report results for people with CKD, evidence gaps in results, and the rate of exclusion of people with CKD. Results We included 1180 of the 2794 eligible RCTs involving 2,158,869 participants (mean age 63±6 years, 36% female). Overall, 841 (71%) RCTs excluded (subgroups of) people with CKD based on heterogenous exclusion criteria. Since 2000, this prevalence has increased from 70% to 75%. Of included RCTs, only 157 (13%) reported results for people with CKD (again in heterogenous subgroups). The prevalence of RCTs with results for people with CKD has increased since 2000 from 10% to 23%. Nevertheless, significant evidence gaps remain for most CVRM interventions, particularly for those with an eGFR <30 ml/min/1.73m2 (22 RCTs), and people who are treated with dialysis (14 RCTs) or received a kidney transplant (1 RCTs). Conclusion(s) The majority of cardiovascular RCTs continues to exclude (subgroups of) people with CKD and this has only increased over the years. Although more RCTs report results for people with CKD, evidence gaps for the efficacy most CVRM medications persist, particularly for those with severe CKD.Figure 1:Heat map (subgroup) analyses for MACE for people with different stages CKD. Panel A illustrates analyses for hypertension, panel B for antiplatelets and anticoagulants, panel C for cholesterol-lowering drugs, panel D for glucose-lowering drugs, and panel E for combinations of interventions.