A Cochrane review [Abstract] 1 included 26 studies with a total of 14 939 subjects with COPD. The median study duration was 6 months (from 3 months to 3 years). Participants were more often male with moderate to severe symptoms; mean FEV1 was between 33% and 55% predicted normal in the studies, and mean St George's Respiratory Questionnaire score (SGRQ) ranged from 44 to 55 when reported. 11 studies compared salmeterol 50μg twice daily with placebo; formoterol 12 μg twice daily was compared with placebo in 14 studies, 3 of them also included a formoterol 24 μg twice-daily arm, and one additional study used only the comparison of formoterol 24 μg. Studies allowed the use of a short-acting beta2-agonist as reliever medication during the study period (salbutamol or terbutaline).
Twice-daily long-acting beta2-agonist (LABA) treatment improved quality of life on the SGRQ and reduced the number of exacerbations requiring hospitalisation (table T1). Scores were also improved on the Chronic Respiratory Disease Questionnaire (CRQ), and more people receiving LABA treatment showed clinically important improvement of at least 4 points on the SGRQ. The number of people who had exacerbations requiring a course of oral steroids or antibiotics was also lower among those taking LABA. Mortality was low, and combined findings of all studies showed that LABA therapy did not significantly affect mortality. LABA therapy did not affect the rate of serious adverse events, although there was significant unexplained heterogeneity, especially between the two formoterol doses. People were more likely to withdraw from placebo than from LABA therapy.
| Outcome | Follow-up | Relative effect(95% CI) | Assumed risk - placebo | Corresponding risk - LABA (95% CI) | Participants(studies) |
|---|---|---|---|---|---|
| Severe exacerbations (hospitalisations) | 7 months | OR 0.73(0.56 to 0.95) | 71 per 1000 | 53 per 1000(40 to 68) | 2 859(7) |
| Moderate exacerbations (course of antibiotics or oral steroids) | 8 months | OR 0.73(0.61 to 0.87) | 238 per 1000 | 186 per 1000(160 to 214) | 3 375(7) |
| All-cause mortality | 14 months | OR 0.90(0.75 to 1.08) | 5 per 1000 | 5 per 1000(4 to 5) | 14 079(23) |
| Participants with one or more serious non-fatal adverse event | 15 months | OR 0.97(0.83 to 1.14) | 86 per 1000 | 84 per 1000(74 to 97) | 12 446(20) |
| Quality of life (SGRQ); lower scores are better* | 16 months | 45.3(mean ofreported placeboendpoints) | Mean score in the intervention groups was2.32 units lower(3.09 to 1.54 lower) | 11 397(17) |
| * A difference of 4 points is generally accepted to be of clinical significance; SGRQ = St George's Respiratory Questionnaire | |||||
| Another Cochrane review [Abstract] 2 included 23 published and unpublished studies with a total of 6061 subjects who had poor reversibility to short-acting bronchodilators (increase in FEV1 of < 200ml and < 15% of the baseline or percent predicted FEV1 after a short acting beta agonist). Majority of the studies investigated the effects of salmeterol 50 mcg versus placebo. There was a significant change in FEV1 in favour of salmeterol 50 mcg twice daily (51 mls, 95% CI 32 to 70; 8 studies, n=2026; high degree of statistical heterogeneity, I2 49%), end of study morning peak expiratory flow (PEF; 14.89 l/min, 95% CI 10.86 to 18.91; n=1467). Supplemental short-acting bronchodilator usage was reduced by just under one puff per day. There were significant differences in the total, activity and impact domain scores of the St George's respiratory questionnaire in favour of salmeterol 50 mcg twice daily. Findings from other health status measurements and symptom scores were conflicting. There was no significant difference in exercise tolerance. The number of participants experiencing exacerbations was significantly reduced with salmeterol 50 mcg treatment compared with placebo (numbers needed to treat to benefit 24).
Comment: The quality of evidence is downgraded by inconsistency (heterogeneity in interventions and outcomes, variability in results across studies). References
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