The British Medical Journal has featured a meta-analysis evaluating the safety of using aliskiren in combination with angiotensin converting enzyme inhibitors or angiotensin receptor blockers.

The meta-analysis included data from published and unpublished randomised controlled trials that compared combined treatment using aliskiren and angiotensin converting enzyme inhibitors or angiotensin receptor blockers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 4 weeks and that provided numerical data on the adverse event outcomes of hyperkalaemia and acute kidney injury.

A total of 10 randomised controlled studies (4,814 participants) were included in the analysis. The following results were reported:

• The risk of hyperkalaemia was statistically significantly higher among participants given aliskiren in combination with an ACE inhibitor or angiotensin receptor blocker than among those given ACE inhibitor or angiotensin receptor blocker monotherapy (relative risk 1.58, 95% confidence interval 1.24 to 2.02; risk difference 0.02, 95% confidence interval 0.01 to 0.04; number needed to harm 43.

• Similarly, the risk of hyperkalaemia from combined use of aliskiren and an ACE inhibitor or angiotensin receptor blocker compared with aliskiren monotherapy was significantly increased (relative risk 1.67, 1.01 to 2.79; risk difference 0.02, 0.03 to 0.01; NNH 50)

• The risk of acute kidney injury was not significantly increased among participants given aliskiren in combination with an ACE inhibitor or angiotensin receptor blocker than among those given ACE inhibitor or angiotensin receptor blocker monotherapy (relative risk 1.14, 0.68 to 1.89) or aliskiren monotherapy (0.80, 0.31 to 2.04)

The researchers highlight several limitations of the meta-analysis but conclude “The use of aliskiren in combination with ACE inhibitors or angiotensin receptor blockers is associated with a significantly increased risk of hyperkalaemia compared with monotherapy using ACE inhibitors or angiotensin receptor blockers. Further research to clarify the role and safety of using aliskiren in combination therapy on important clinical outcomes is needed.”