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.
Author(s): Harel Z, Gilbert C, Wald R, Bell C, Perl J, Juurlink D, Beyene J, Shah PS.
Affiliation(s): Division of Nephrology, St Michael's Hospital, University of Toronto, ON,
Toronto, Canada M5B 1W8. harelz@smh.ca
Publication date & source: 2012, BMJ. , 344:e42
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STUDY SELECTION: Published and unpublished randomised controlled trials that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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