“Renalism” with Renin Angiotensin Aldosterone System Inhibitor Use in Patients Enrolled in Trials for Heart Failure with Reduced Ejection Fraction and Advanced Chronic Kidney Disease: A Systematic Review

Introduction: Angiotensin-converting enzyme inhibitors (ACEI), angiotensin receptor blockers (ARB), angiotensin receptor-neprilysin inhibitor (ARNI), and mineralocorticoid receptor antagonists (MRA) reduce mortality and hospitalizations in heart failure with reduced ejection fraction (HFrEF) but their use is limited in advanced chronic kidney disease (CKD). Methods: We carried out a systematic review of studies on HFrEF and CKD patients. The mean overall percentage of reported ACEI, ARB, MRA, and ARNI use, and the proportion of trials that included patients with advanced CKD grades 4-5 (estimated glomerular filtration rate (eGFR) <15-30 ml/min/1.73m2) were recorded per year. The proportion of trials with advanced CKD was logtransformed, and then fitted into a time regression model. The interactions between the proportion of trials that included CKD grades 4-5 and the proportion of reported use of ACEI, ARB, and MRAs per year were explored using Pearson’s correlation and univariate linear regression. Results: A total of 706 articles were included; 76% reported background ACEI/ARB use, while 51% reported MRA use. ACEI/ARB use averaged 83% and MRA 50%. Of the trials, 57% included CKD grades 4-5. Over 10 years, the proportion of trials with CKD grades 4-5 increased while ACEI/ARB use decreased. MRA use rates remained about the same. There was an inverse association found between the proportion of trials with CKD grades 4-5 and ACEI/ARB use per year. Conclusion: In the past 10 years, CKD grades 4-5 patients have been increasingly included in HFrEF clinical trials. Concurrently, ACEI/ARB use has reportedly decreased.