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Serum creatinine elevation after renin-angiotensin system blockade and long term cardiorenal risks: cohort study

BMJ 2017; 356 doi: https://doi.org/10.1136/bmj.j791 (Published 09 March 2017) Cite this as: BMJ 2017;356:j791

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Re: Serum creatinine elevation after renin-angiotensin system blockade and long term cardiorenal risks: cohort study

Schmidt and colleagues use a retrospective analysis of a population-based UK cohort to suggest that patients who have an increase in creatinine during treatment with ACE-I/ARB have an increased risk of ESRD, myocardial infarction, heart failure and death than those treated with an ACE-I/ARB whose creatinine measurements do not change. Although the authors caution against discontinuing ACE/ARB we worry that primary care physicians who read the article will feel compelled to do just so.

While the authors have done meticulous data analysis including an extensive sensitivity analysis, we have concerns regarding the design of the study. Creatinine measurements done as much as a year prior to initiating ACE/ARB were considered as baseline creatinine level, and there was no data presented to show that renal function was stable prior to initiating therapy with ACE-I/ARB. Thus, an alternative interpretation of the data is that patients whose creatinine levels rise have an increased risk of these outcomes, and that the effect of the ACE-I/ARB therapy, whether it increases or whether it decreases this risk, is completely unknown. Worsening renal function is well known to predict adverse cardiac and renal outcomes. We are not certain that the design of the study clearly demonstrates that the change in renal function was due to ACE-I/ARB therapy as opposed to progression of underlying disease. Moreover, we do not know whether the patients with ACE-I/ARB therapy who had an increase in their serum creatinine did better or worse than those with similar clinical characteristics who did not receive this therapy or those whose ACE-I/ARB was discontinued. The question of the impact of ACE-I/ARB therapy on clinical outcomes has substantial public health implications.

We hope that studies that provide the appropriate comparison group will be forthcoming. Until then, we hope that the authors of this paper will agree that the results of this report are insufficient to determine whether ACE-I/ARB therapy was beneficial or harmful. Until the results of such a trial are available we caution against changing current clinical practice based on results of retrospective analysis.

Competing interests: No competing interests

27 June 2017
Olanrewaju A. Olaoye
Physician
Rajesh Mohandas MD. MPH.
University of Florida
Division of Nephrology, Hypertension & Transplantation CG-98, PO Box 100224 1600 SW Archer Road University of Florida Academic Health Center Gainesville, FL-32610 Tel: 352-273-5355 Fax:352-392-5465