Hello. This is Jeffrey Berns, editor-in-chief of Medscape Nephrology. I recently gave a talk to a group of primary care providers about chronic kidney disease (CKD) and was asked about the comparative efficacy of angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) for slowing the progression of CKD.
I responded that I considered them to be interchangeable in this regard. I also mentioned a study from a number of years ago that suggested that ARBs may be less likely to cause hyperkalemia compared with ACE inhibitors, although I couldn't remember seeing anything since that study many years ago.
The next day, when I came to the office, I just happened to see a new paper that came out in the American Journal of Kidney Diseases by Xie and colleagues,[1] who reported a Bayesian network meta-analysis of randomized controlled trials assessing kidney function and mortality outcomes with ACE inhibitors, ARBs, placebo, and other active controls such as calcium channel blockers. This type of analysis, which was described in an accompanying editorial as the new norm for meta-analyses, basically takes a variety of independent separate studies and does a pseudo head-to-head comparison of one study group versus another by aggregating the findings from each of these separate studies.
So, although there were only four studies that directly compared ACE inhibitors with ARBs for renal outcomes, this analysis allowed a broader assessment by taking outcomes from different groups and different studies and comparing them. You get more ACE inhibitor-to-ARB comparisons than just looking at the individual studies that directly did that.
Before I get to those findings, I did look back into the potassium effect of ACE inhibitors and ARBs. The study I recalled was from 2000 by Bakris and colleagues.[2] It was a small randomized controlled trial with only 35 patients, with a crossover design comparing lisinopril with valsartan. There was less hyperkalemia with valsartan among patients with glomerular filtration rates (GFRs) < 60 mL/min/1.73 m2 with an increase in the potassium of 0.12 versus 0.28 mEq/L with lisinopril. Not much else is in the literature about this, although I did find another study[3] from 2002 in type 2 diabetics that found no difference between candesartan and lisinopril.
A retrospective study[4] in 2009 looked at patients who were treated at a VA hospital. The authors found that both mild and severe hyperkalemia were more common among patients treated with ARBs than ACE inhibitors, although it's difficult to know what to make of this type of retrospective analysis in this regard. For now, I think I'll go with the Bakris paper; there may be a slight benefit with ARBs compared with ACE inhibitors for a potassium effect. We definitely need additional studies in this area.
So, back to the paper by Xie. I'll only comment on the renal outcomes, although there were others, as I've mentioned. This paper defined kidney failure as doubling of the serum creatinine, halving of the GFR, or development of end-stage renal disease. ACE inhibitors and ARBs were noted to reduce renal failure events by about 30%-40% compared with placebo and other active controls such as calcium channel blockers. When they compared ACE inhibitors and ARBs against one another, they found no statistically significant difference between the two drug classes.
They went a step further, which was a little bit odd, and indicated that there was an 81% chance that ACE inhibitors were better for kidney outcomes than ARBs and only a 19% chance that ARBs were better.
An accompanying editorial[5] criticized this ranking analysis as opposed to just relying on the conventional effects analysis with routine statistics. The authors of the editorial also noted that a randomized controlled trial of over 25,000 patients found no difference between these drugs. Also of note is that this Bayesian meta-analysis did not find a difference in hyperkalemia as an adverse event between ACE inhibitors and ARBs.
My takeaway is that there is probably an indistinguishable difference in benefit between ACE inhibitors and ARBs on CKD and renal failure outcomes. There may be a small effect in favor of ARBs for hyperkalemia.
Clearly, ACE inhibitors and ARBs are superior to taking nothing or drugs of other classes. Therefore, it's important to get all of our patients who ought to be on ACE inhibitors or ARBs on them for their renoprotective effects.
Thanks for listening. This is Jeffrey Berns, editor-in-chief of Medscape Nephrology, from the Perelman School of Medicine at the University of Pennsylvania in Philadelphia.
Medscape Nephrology © 2016 WebMD, LLC
Any views expressed above are the author's own and do not necessarily reflect the views of WebMD or Medscape.
Cite this: ACE Inhibitors vs ARBs in CKD: A Toss-up? - Medscape - Aug 02, 2016.
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