ACE + ARB = Adverse Events

No Benefit, Possible Harm With Dual Blockade in Diabetic Nephropathy

Jeffrey S. Berns, MD


December 17, 2013

This feature requires the newest version of Flash. You can download it here.

Hello. This is Jeffrey Berns, Editor-in-Chief of Medscape Nephrology.

Do you have patients in your practice who are on combined renin-angiotensin-aldosterone system (RAAS) blockade with an angiotensin receptor blocker (ARB) and an angiotensin-converting enzyme (ACE) inhibitor? If so, you probably ought to think about stopping one or the other of those drugs.

I call to your attention a paper just published in the New England Journal of Medicine, with Linda Fried as the first author.[1] This was an excellent randomized controlled trial among US veterans, almost all men, with type 2 diabetes, a urinary albumin/creatinine ratio greater than 300 mg/g creatinine, and an estimated glomerular filtration rate (GFR) between 30 and 89.9 mL/min/1.73 m2.

After participants with elevated serum potassium levels at baseline were excluded, the subjects were placed on losartan 100 mg/day, and once stable on that dose, were then randomly assigned to receive either placebo or lisinopril in a dose of 10-40 mg/day.

The study was stopped early. The drug combination provided no benefit to major primary and secondary endpoints of the study, which included the rate of GFR decline, occurrence of cardiovascular events, occurrence of end-stage renal disease, or mortality. On average, the GFR declined between 2.7 and 2.9 mL/min/1.73 m2 per year.

In addition, patients receiving the active drug combination had an excess occurrence of hyperkalemia and acute kidney injury. The hazard ratio for hyperkalemia was 2.8, and for acute kidney injury, it was 1.7. No benefit, excess risk, and the study was stopped early.


Comments on Medscape are moderated and should be professional in tone and on topic. You must declare any conflicts of interest related to your comments and responses. Please see our Commenting Guide for further information. We reserve the right to remove posts at our sole discretion.
Post as: