Twenty seven RCTs (n=20,527) were included in the review. RCTs scored between 3 and 5 on the Jadad scale, with five studies scoring 5.
Significantly fewer incidences of severe COPD exacerbations were reported in patients receiving LABA compared to placebo. RR reduction was 0.78 (95% CI: 0.67, 0.91, p<0.001, I2=0%) (14 RCTs). The NNT was 30 (95% CI: 20, 52).
RCTs reporting one or more deaths reported no significant differences between patients in the LABA and placebo groups for all-cause mortality (nine of 13 RCTs) or respiratory deaths (five of 12 RCTs). Subgroup analyses (two RCTs) showed significant reductions in respiratory deaths in patients receiving LABA combined with ICS compared to LABA monotherapy; RR 0.35 (95% CI: 0.14, 0.93, p=0.03, I2=0%).
Significant benefits in airflow limitation measures, health-related quality of life, and use of rescue medication were reported in patients receiving LABAs. However, there was significant heterogeneity among studies reporting the two former outcomes (I2=92% and I2=83%, respectively). Fewer incidences of severe COPD exacerbations were reported in patients receiving tiotropium compared with patients receiving LABAs (three RCTs); RR 0.52 (95% CI: 0.31, 0.87). Again, there was evidence of significant heterogeneity (I2=57.6%).
ARRs and adjustments for publication bias were reported in the review.