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Meta-Analysis
. 2012 Jan 9:344:e42.
doi: 10.1136/bmj.e42.

The effect of combination treatment with aliskiren and blockers of the renin-angiotensin system on hyperkalaemia and acute kidney injury: systematic review and meta-analysis

Ziv Harel  1 , Cameron Gilbert, Ron Wald, Chaim Bell, Jeff Perl, David Juurlink, Joseph Beyene, Prakesh S Shah
Affiliations
Meta-Analysis

The effect of combination treatment with aliskiren and blockers of the renin-angiotensin system on hyperkalaemia and acute kidney injury: systematic review and meta-analysis

Ziv Harel et al. BMJ. .

Abstract

Objective: To examine the safety of using aliskiren combined with agents used to block the renin-angiotensin system.

Design: Systematic review and meta-analysis of randomised controlled trials.

Data sources: Medline, Embase, the Cochrane Library, and two trial registries, published up to 7 May 2011.

Study selection: Published and unpublished randomised controlled trials that compared combined treatment using aliskiren and angiotensin converting enzyme inhibitors or angiotensin receptor blockers with monotherapy using these agents for at least four weeks and that provided numerical data on the adverse event outcomes of hyperkalaemia and acute kidney injury. A random effects model was used to calculate pooled risk ratios and 95% confidence intervals for these outcomes.

Results: 10 randomised controlled studies (4814 participants) were included in the analysis. Combination therapy with aliskiren and angiotensin converting enzyme inhibitors or angiotensin receptor blockers significantly increased the risk of hyperkalaemia compared with monotherapy using angiotensin converting enzymes or angiotensin receptor blockers (relative risk 1.58, 95% confidence interval 1.24 to 2.02) or aliskiren alone (1.67, 1.01 to 2.79). The risk of acute kidney injury did not differ significantly between the combined therapy and monotherapy groups (1.14, 0.68 to 1.89).

Conclusion: Use of aliskerin in combination with angiotensin converting enzyme inhibitors or angiotensin receptor blockers is associated with an increased risk for hyperkalaemia. The combined use of these agents warrants careful monitoring of serum potassium levels.

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Conflict of interest statement

Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/coi_disclosure.pdf (available on request from the corresponding author) and declare no support from any organisation for the submitted work; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; and no other relationships or activities that could appear to have influenced the submitted work.

Figures

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Fig 1 Flow of studies through review
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Fig 2 Risk of hyperkalaemia among participants given combined aliskiren and angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) versus monotherapy (ACE inhibitor, ARB, or aliskiren). Values less than 1.0 indicate a decreased risk of outcome with combination therapy
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Fig 3 Risk of acute kidney injury among participants given combined aliskiren and angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) versus monotherapy (ACE inhibitor, ARB, or aliskiren). Values less than 1.0 indicate a decreased risk of outcome with combination therapy
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Fig 4 Risk of hyperkalaemia stratified by severity among participants given combination therapy with aliskiren and angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) versus monotherapy with ACE inhibitor or ARB. Values less than 1.0 indicate a decreased risk of outcome with combination therapy
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Fig 5 Risk of severe hyperkalaemia stratified by high and low risk participants given combination therapy with aliskiren and angiotensin converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) versus monotherapy with ACE inhibitor or ARB. Values less than 1.0 indicate a decreased risk of outcome with combination therapy
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Comment in

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