Blog entry by Meguid El Nahas

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by Meguid El Nahas - Friday, 20 December 2013, 12:37 PM
Anyone in the world
JAMA Intern Med. 2013 Dec 16. doi: 10.1001/jamainternmed.2013.12700. [Epub ahead of print]

Renoprotective Effect of Renin-Angiotensin-Aldosterone System Blockade in Patients With Predialysis Advanced Chronic Kidney Disease, Hypertension, and Anemia.

Abstract

IMPORTANCE The benefit of using a renin-angiotensin-aldosterone system blocker such as an angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin II receptor blocker (ARB) for patients with advanced chronic kidney disease (CKD) remains undetermined. OBJECTIVE To assess the effectiveness and safety of ACEI/ARB use for advanced predialysis CKD in patients with hypertension and anemia. DESIGN Prospective cohort study. SETTING Taiwan. PARTICIPANTS From January 1, 2000, through June 30, 2009, we selected 28 497 hypertensive adult patients with CKD. Serum creatinine levels were greater than 6 mg/dL, hematocrit levels were less than 28%, and patients were treated with erythropoiesis-stimulating agents. INTERVENTIONS Users (n = 14 117) and nonusers (n = 14 380) of ACEIs/ARBs. MAIN OUTCOMES AND MEASURES We used Cox proportional hazards regression models to estimate hazard ratios (HRs) for commencement of long-term dialysis and all-cause mortality for ACRI/ARB users vs nonusers. RESULTS In a median follow-up of 7 months, 20 152 patients (70.7%) required long-term dialysis and 5696 (20.0%) died before progression to end-stage renal disease requiring dialysis. Use of ACEIs/ARBs was associated with a lower risk for long-term dialysis (HR, 0.94 [95% CI, 0.91-0.97]) and the composite outcome of long-term dialysis or death (0.94 [0.92-0.97]). The renal benefit of ACEI/ARB use was consistent across most patient subgroups, as was that of ACEI or ARB monotherapy. Compared with nonusers, the ACEI/ARB users had a higher hyperkalemia-associated hospitalization rate, but the risk of predialysis mortality caused by hyperkalemia was not significantly increased (HR, 1.03 [95% CI, 0.92-1.16]; P = .30). CONCLUSIONS AND RELEVANCE Patients with stable hypertension and advanced CKD who receive therapy with ACEIs/ARBs exhibit an association with lower risk for long-term dialysis or death by 6%. This benefit does not increase the risk of all-cause mortality.

COMMENTS:

Having read this article more than once, I find it somewhat incoherent and also potentially misleading.

Before, I go any further, let me declare my serious conflict of interest with this publication...I personally think it is abhorrent to start ACE inhibitors and even to continue them in CKD stage5...and I also published 2 papers to the effect that stopping ACE inhibtiorts in CKD4-5 is BENEFICIAL with renal functional recovery in a majority:

http://www.ncbi.nlm.nih.gov/pubmed/19820248

http://www.ncbi.nlm.nih.gov/pubmed/22135795

Now, that is out of the way...lets look at this publication from China that pretends that RAS inhibiton delays ESRD in CKD5 and improves survival.

1. It isnt clear at all when RAS inhibitors where started or even STOPPED in this publication, other than the fact that patients HAD been on an ACEi and/or ARB: inclusion criteria most unusual and most confusing:

"...patients who had taken any ACEI/ARB within 90 days after the first ESA prescription were defined as ACEI/ ARB users; the remaining patients were defined as ACEI/ARB nonusers...."

whether they took it for a day...or a year...whether they were still on them or not....seems lost in translation...

2. Follow-up period of 7 months, is far to short to ascertain any impact on mortality; regardless of how high the mortality of CKD5 in Taiwan is...

3. Looking at the figures, I strained my eyes to see a difference between the ESRD and composite ESRD + survival lines...although the p value is statistically significant, I very much doubt th eclinical relevance of the number needed to treat (NNT) to prevent a Single death.

4. Is the use of composite endpoint a misleading way/ploy to hide the lack of impact on survival...or to imply a protection by linking it to ESRD delay...??? Statistics...statistics...statistics...and their manipulations to serve researchers and their sponsors objectives...?!

5. The whole paper striking as lacking information about one thing: BLOOD PRESSURE and its control. This is hardly mentioned knowing how poorly BP is controlled in Chinese community. A topic we previously commented upon:

http://www.ncbi.nlm.nih.gov/pubmed/19059042

6. The authors even advocate DUAL BLOCKADE as protective, when the rest of the world deems it contraindicated in view of its increased morbidity and mortality; see ONTARGET and Subsequent publications.

It is disturbing that such poor quality publications find their way to top medical journals.

It is disturbing that reviewers in such journals are incapable of critically appraise a manuscript.

It is disturbing to see that misleading and potentially dangerous message unchallenged by an editorial to moderate its impact.

JAMA has a lot to answer!

 

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