Lowering the dose of renin-angiotensin-aldosterone system inhibitors (RAASi) to prevent hyperkalemia may increase the risk for major adverse cardiovascular events (MACE) among patients with chronic kidney disease (CKD) and heart failure, according to new research published in the Journal of the American Heart Association.

Cecilia Linde, MD, PhD, of Karolinska University Hospital in Sweden, and colleagues conducted a real-world analysis of 100,572 patients with new-onset CKD stage 3 to 5 (not on dialysis) and 13,113 patients with new-onset heart failure from the United Kingdom’s Clinical Practice Research Datalink and Hospital Episode Statistics databases. Angiotensin-converting enzyme inhibitors (ACEis) were the most commonly prescribed RAASi among patients with CKD (76.4%) and heart failure (73.5%). Angiotensin receptor blockers (ARBs) were more frequently prescribed in CKD than heart failure (32.1% vs 25.1%), whereas the reverse was observed for mineralocorticoid receptor antagonists (MRAs; 9.6% vs 43.0%).

RAASi dosing was based on the 2016 European Society of Cardiology (ESC) guidelines for the treatment of heart failure. Clinicians commonly underprescribed RAASi, especially after hyperkalemia episodes. CKD and heart failure patients with serum potassium levels of 5.0 mmol/L or higher had a 79% and 33% higher risk of RAASi down-titration, respectively, than normokalemic patients.

Continue Reading

In addition, 41.8% of RAASi prescriptions for CKD patients and 36.5% for heart failure patients were for less than 50% of the ESC guideline-recommended dose. Importantly, CKD patients receiving a lower dose had a 5.6-fold higher risk for death and a 1.6-fold higher risk for MACE compared with patients receiving 50% or more of the recommended dose. Heart failure patients with a lower dose also had a 7.3- and 1.9-fold higher risk for death and MACE, respectively.

“Results of this study emphasize the potential negative impact of suboptimal RAASi dosing and, consequently, the need for strategies that allow patients to be maintained on appropriate therapy, avoiding RAASi dose modification or discontinuation,” Dr Linde’s team wrote. “We propose that European Society of Cardiology-recommended RAASi doses for patients with heart failure may be generalizable to chronic kidney disease patients in the absence of chronic kidney disease-specific recommendations.”

This study was funded by AstraZeneca.

Related Articles


Linde C, Bakhai A, Furuland H, et al. Real-world associations of renin–angiotensin–aldosterone system inhibitor dose, hyperkalemia, and adverse clinical outcomes in a cohort of patients with new-onset chronic kidney disease or heart failure in the United Kingdom. J Am Heart Assoc. 2019;8:e012655. doi:10.1161/JAHA.119.012655