Ten RCTs (n=4,814 patients) were included in the review. One trial was excluded due to insufficient data (no reply from the authors). The risk of bias was judged to be low across the included trials (more details reported in paper). The lack of masking in some trials was felt to be less relevant given the laboratory-based safety outcomes being assessed. Withdrawal rates were less than 20% in all trials.
Hyperkalaemia: The risk of hyperkalaemia was significantly higher in patients given combined aliskiren and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker therapy compared with patients given angiotensin-converting enzyme inhibitor/angiotensin receptor blocker as monotherapy (RR 1.58, 95% CI 1.24 to 2.02; NNH 43, 95% CI 28 to 90; 10 trials; n=4,814). The risk of hyperkalaemia was significantly higher in patients given combined aliskiren and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker therapy compared with patients given aliskiren as monotherapy (RR 1.67, 95% CI 1.01 to 2.79; NNH 50, 95% CI 33 to 125; six trials; n=2,974).
Acute kidney injury: The risk of acute kidney failure was not significantly greater in patients given combined aliskiren and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker therapy compared with patients given angiotensin-converting enzyme inhibitor/angiotensin receptor blocker as monotherapy (eight trials; n=4,345) or in patients who were given combined aliskiren and angiotensin-converting enzyme inhibitor/angiotensin receptor blocker therapy compared with patients given aliskiren as monotherapy (five trials; n=3,063).
No significant heterogeneity was observed for any of the analyses.
Further analyses including comparisons of moderate and severe hyperkalaemia, and a retrospective sensitivity analysis were reported in the paper.
Publication bias was not observed.