Continuing ACE Inhibitors Despite Potassium Change Can Have Benefits

Stopping renin-angiotensin-aldosterone inhibitors after hyperkalemia may offset their potential clinical benefits, according to investigators.

Continuation of angiotensin-converting enzyme (ACE) inhibitor therapy is associated with better clinical outcomes, despite early fluctuation in serum potassium, according to investigators.

In a post hoc analysis of the Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation (ADVANCE) trial, investigators examined data from 9694 patients with type 2 diabetes (aged 55 years and older) with normokalemia who initiated fixed-dose perindopril-indapamide due to their high risk for cardiovascular events. After a 6-week run-in period in the original trial, patients were randomly assigned to continue ACE inhibitor therapy or receive placebo.

Using the serum potassium value at 3 weeks after ACE inhibitor initiation, investigators classified patients into hyperkalemia (5.0 mEq/L or higher in 5.6%), normokalemia (93.2%), and hypokalemia (less than 3.5 mEq/L in 1.0%) groups.

Over a median 4.4 years, 1505 patients (15.5%) experienced the primary composite outcome of major macrovascular and microvascular events.

ACE inhibitor continuation significantly decreased the risk of the primary outcome by 9% with an absolute difference of 38.1 vs 42.0 per 1000 person-years with placebo, Toshiaki Ohkuma, PhD, of The George Institute for Global Health, University of New South Wales in Australia, and colleagues reported in the Clinical Journal of the American Society of Nephrology. ACE inhibitor therapy also significantly decreased the risk of all-cause death and cardiovascular death by 14% and 18%, respectively. Effect magnitude did not differ significantly by serum potassium subgroup.

“These findings suggest that discontinuation of [renin-angiotensin-system] inhibitor-based therapy after hyperkalemia may diminish the benefits in terms of reduction in the long-term risk of vascular events and death, although close attention to severe hyperkalemia, which can cause life-threatening arrhythmias, is needed,” Dr Ohkuma’s team concluded. Additional interventional studies are needed to confirm the findings.

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.


Ohkuma T, Harris K, Cooper M, et al. Short-term changes in serum potassium and the risk of subsequent vascular events and mortality: Results from a randomized controlled trial of ACE inhibitors. Clin J Am Soc Nephrol. 2022 Aug;17(8):1139-1149. doi:10.2215/CJN.00180122

This article originally appeared on Renal and Urology News