Large Swedish Study Says Stopping RAS Inhibitors Leads to Worse CKD Outcomes

A new study from Sweden cautions against routine discontinuation of renin-angiotensin system (RAS) inhibitors in patients with chronic kidney disease.

Small, single-center studies have suggested that RAS inhibitors may be harmful in CKD and providers often stop the treatment, leading to delays in starting dialysis, or kidney replacement therapy (KRT), although large, prospective studies assessing cardiovascular and kidney outcomes in this group of patients are lacking.

Patients use RAS blockers for hypertension, cardiovascular disease, heart failure, and CKD. However, not enough is known about their efficacy and safety in patients with advanced CKD, as that population was underrepresented in pivotal randomized trials.

Researchers at Karolinska Institutet and elsewhere conducted the epidemiological study using data from the Swedish Renal Registry to evaluate over 10,000 patients with advanced CKD who received RAS inhibitors from 2007–2017 and who then developed advanced CKD (eGFR<30 ml/min per 1.73 m2.

The study of 10,254 Swedish patients, published in The Journal of the American Society of Nephrology, showed that ending the treatment was linked with increases in the 5-year absolute risks of mortality and major adverse cardiovascular events—13.6% and 11.9%, respectively—and an 8.3% decrease in absolute risk of beginning dialysis.

"The use of RAS inhibitors in patients with advanced CKD is controversial, and many doctors deprescribe them," principal investigator Juan Jesus Carrero, professor at the Department of Medical Epidemiology and Biostatistics at Karolinska, said in a statement. "Rather than routinely discontinuing treatment, our results show that the issue is a complex one and that doctors must carefully weigh the protective effects of RAS inhibitors on the cardiovascular system against the potential harms on the kidneys. Until clinical trials are performed, this evidence supports continued use of this lifesaving therapy in patients with advanced CKD who are doing well on the medications."

He noted that sometimes these medications may have to be stopped for other reasons, for example, if patients have persistently high blood potassium levels that don't respond to management.