Prescribing Advice for GPs

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Tiotropium versus Salmeterol in COPD

The New England Journal of Medicine has published the results of a trial that aimed to assess the efficacy of tiotropium versus salmeterol in preventing exacerbations in patients with chronic obstructive pulmonary disease (COPD). The study is being referred to as the Prevention Of Exacerbations with Tiotropium in COPD (POET-COPD) trial.

The trial recruited 7,376 patients with moderate to very severe COPD and a history of exacerbations in the previous year. The trial was randomised and double blind by design. 3,707 patients were assigned to treatment with 18 micrograms of tiotropium daily while 3,669 patients were assigned to treatment with 50 micrograms of salmeterol twice daily via a metered dose aerosol inhaler. To maintain adequate blinding, patients were issued with a corresponding placebo device.

The study ran for 1 year with a primary end point of time to first exacerbation. Secondary endpoints included annual number of moderate to severe exacerbations and annual number of severe exacerbations.

Treatment with tiotropium increased the average time to a first exacerbation from 145 days to 187 days. It also increased the time to a first severe exacerbation, decreased the annual number of moderate to severe exacerbations from 0.72 to 0.64 (rate ratio 0.89, 95% CI, 0.83 - 0.96, P=0.002) and decreased the annual number of severe exacerbations from 0.13 to 0.09 (rate ratio 0.73, 95% CI, 0.66 to 0.82, P<0.001).

The authors conclude that, "in patients with moderate-to-very-severe COPD, tiotropium is more effective than salmeterol in preventing exacerbations". Adverse event and discontinuation rates were similar in both study groups.

This study does provide some valuable data however there are limitations. Tiotropium was compared to salmeterol in a metered dose aerosol inhaler so it is unclear how dry power device would compare. Also, the study was not of long enough duration to assess if the reduction in exacerbations produced an increase in life expectancy.

Action: Clinicians should be aware of this study. The current NICE guideline for COPD places tiotropium (a long acting muscarinic antagonist or LAMA) and salmeterol (a long acting beta agonist or LABA) at the same level. Based on this study clinicians may wish to consider using a LAMA in favour of a LABA where appropriate.

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