Fast track — ArticlesCombined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: a randomised controlled trial
Introduction
Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity worldwide. It is characterised by chronic progressive symptoms, airflow obstruction,1, 2 and impaired health status,3 which is worse in those who have frequent, acute episodes of symptom exacerbation.4 The aim of treatment is to prevent and control symptoms and exacerbations while improving lung function and health status.5, 6 Any new treatment approach should be judged against these endpoints.
Inhaled long-acting β2 agonists improve airflow obstruction, control of symptoms, and health status in patients with COPD over 3–4 months7, 8, 9, 10, 11, 12, 13, 14 and have several potentially beneficial non-bronchodilatory effects.15 The role of inhaled corticosteroids in COPD management is less certain.16 These drugs do not change the rate of decline in lung function,17, 18, 19, 20 but can increase postbronchodilator forced expiratory volume in 1 s (FEV1),17, 19 reduce the number of exacerbations,17, 18 and slow the rate of decline in health status.17 Whether long-acting β2 agonists and inhaled corticosteroids in combination will result in treatment effects that are better than those associated with either drug alone is not clear. Furthermore, we do not know whether improvements seen in the short term will be maintained during sustained treatment. To test our hypothesis, we did a randomised controlled trial over 1 year of combination treatment with salmeterol and fluticasone versus each of the components and placebo.
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Patients
We recruited outpatients with COPD from 196 hospitals in 25 countries. All patients had a baseline FEV1 before bronchodilation that was 25–70% of that predicted, an increase of less than 10% of predicted FEV1 30 min after inhaling 400 μg salbutamol, and a prebronchodilator FEV1/forced vital capacity (FVC) ratio of 70% or less.21 Patients also had a history of at least 10 pack-years of smoking (ie, equivalent to 20 cigarettes smoked per day for 10 years), of chronic bronchitis, at least one
Results
We recruited 1974 patients from 196 centres in 25 countries, of whom 1465 received treatment (figure 1). Demographic data, baseline characteristics, and compliance did not differ between groups, but the withdrawal rate did. Significantly fewer patients withdrew from the combination and fluticasone groups than from placebo and salmeterol groups (Table 1). The main reason for differences in withdrawal was presence of adverse events. Patients in the combination group had a slightly higher mean
Discussion
Ideally, any new treatment for COPD should improve one or more of the endpoints outlined in the GOLD (Global Initiative for Chronic Obstructive Lung Disease) management protocol25—symptoms, health status, and frequency of exacerbation. These effects should be sustained and better than those of existing treatments. Many treatment trials in COPD have only lasted 3–6 months,18, 26 or if longer, they have compared only one active treatment with placebo. Our trial has compared commonly prescribed
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