Seventeen RCTs (n=3,291 participants) were included in the meta-analysis. There were 12 parallel group and five cross-over trials. Fourteen trials were considered to be at high risk of bias due to unclear allocation concealment and inadequate description of blinding. Withdrawal rates were less below 20% in most cases.
Combination treatment was associated with a statistically significant greater reduction in clinical systolic blood pressure (WMD 5.72, 95% CI 4.10 to 7.33; 11 trials) and clinical diastolic blood pressure (WMD 3.62, 95% CI 4.85 to 2.39; 11 trials). Subgroup and meta-regression analyses revealed no substantial influences on the primary outcome. Combination treatment showed greater reductions in mean ambulatory systolic blood pressure (WMD 4.24, 95% CI 6.82 to 1.67) and diastolic blood pressure (WMD 2.23, 95% CI 3.73 to 0.69) over a 24-hour period and a higher therapeutic rate (RR 1.36, 95% CI 1.07 to 1.73; five trials).
Overall adverse events (RR 0.86, 95% CI 0.75 to 0.99; eight trials) and oedema (RR 0.40, 95% CI 0.29 to 0.56; 11 trials) were significantly lower following combination treatment. Cough rate increased (RR 3.28, 95% CI 2.03 to 5.29; nine trials). There was no evidence of publication bias.
Sensitivity analysis demonstrated the robustness of the results.