Eligibility of Patients With CKD for Cardiovascular RCTs

Patients with chronic kidney disease (CKD) are ineligible for participation in many randomized, controlled trials (RCTs). In a pilot study presented at the 61st European Renal Association Congress, Julia Colombijn and fellow researchers examined the eligibility of patients with CKD for five major cardiovascular RCTs and the reasons for ineligibility. The CREDENCE, DAPA-CKD, CIBIS II, CIBIS III, and AUGUSTUS studies were included.

The research team included patients from the Utrecht Patient Oriented Database (UPOD) with CKD, defined as estimated glomerular filtration rate (eGFR) 3 mg/mmol for >3 months. Eligibility criteria were extracted from the five RCTs and modeled on the patients from UPOD. A total of 9005 UPOD patients were included in the pilot study. Mean age was 65 ± 14 years, and 42% were female. Mean eGFR was 49 ± 17 mg/mmol; 1741 (19%) participants had a history of atherosclerotic cardiovascular disease, while 765 (8%) had a history of heart failure.

The researchers found that less than 3% of patients with CKD in routine clinical practice would be eligible to participate in cardiovascular RCTs. Just 0.05% of patients would be eligible for the DAPA-CKD trial and 0% for the CREDENCE trial. Of pilot study subjects with heart failure, 2% would have been eligible for CIBIS II and 3% for CIBIS III. Of those participants with coronary artery disease, 2% would have been eligible for AUGUSTUS.

Prevalent reasons for ineligibility included not meeting inclusion criteria for urine albumin-creatinine ratio, eGFR, or prescription of renin-angiotensin-aldosterone system inhibitors. For CIBIS II, other reasons for ineligibility included not fulfilling the inclusion criteria for left ventricular ejection fraction (LVEF; 50%) or prescription of an angiotensin-converting enzyme inhibitor (42%) or diuretic (33%). CIBIS III ineligibility was often due to not meeting the inclusion criteria for age (46%), LVEF (46%), or prescription of diuretics (31%). For AUGUSTUS, the primary reasons for ineligibility were not fulfilling the inclusion criteria of atrial fibrillation (79%) or percutaneous coronary interventions (91%). Not fulfilling certain exclusion criteria was also a major cause of ineligibility for each study.

The widespread exclusion of people with CKD from cardiovascular RCTs could limit such studies’ generalizability for patients with CKD treated in a clinical setting. The pilot study authors wrote that, “to improve generalizability, RCTs in patients with CKD should aim to include more patients who reflect the patients with CKD treated in practice.”

Source: Colombijn J, Huis in ’t Veld L, Kusters M, et al. Generalisability of cardiovascular RCTs to patients with chronic kidney disease in clinical practice: a comparison between RCTs and real-world data. Abstract #615. Presented at the 61st European Renal Association Congress; May 23-26, 2024; Stockholm, Sweden.