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"Salmeterol and Fluticasone Propionate and Survival in Chronic Obstructive Pulmonary Disease". The New England Journal of Medicine. 2007. 356(8):775-789. PubMed•Full text•PDFContents 1Clinical Question 2Bottom Line 3Major Points 4Guidelines 5Design 6Population 6.1Inclusion Criteria 6.2Exclusion Criteria 6.3Baseline Characteristics 7Interventions 8Outcomes 8.1Primary Outcomes 8.2Secondary Outcomes 9Criticisms 10Funding 11Further Reading

Clinical Question

Does the combination of the long-acting beta-agonist salmeterol and the inhaled corticosteroid fluticasone propionate reduce mortality among patients with chronic obstructive pulmonary disease (COPD)?

Bottom Line

The combination of salmeterol and fluticasone propionate did not significantly reduce all-cause mortality in COPD when compared to placebo. It did, however, reduce exacerbations and improve health status and lung function.

Major Points

Guidelines

Current guidelines for the management of COPD recommend combination therapy with inhaled corticosteroids and long-acting beta-agonists for patients with frequent exacerbations.

Design

Population

A total of 6,112 patients with a history of smoking and moderate to severe COPD participated.

Inclusion Criteria
- Age 40 to 80 years
- History of smoking with at least a 10-pack-year history
- Diagnosed COPD with post-bronchodilator FEV1 less than 60% of the predicted value and less than a 10% increase in FEV1 post 400 μg albuterol administration

Exclusion Criteria
- Patients previously on certain COPD medications and those with other significant respiratory disorders were excluded.

Baseline Characteristics
- Mean age was 65 years
- Mean FEV1 was 44% of the predicted value

Interventions

Patients were randomized to receive either a combination of salmeterol (50 μg) and fluticasone propionate (500 μg) twice daily, salmeterol alone, fluticasone propionate alone, or placebo.

Outcomes

Primary Outcomes
- 12.6% mortality in the combination therapy group vs. 15.2% in the placebo group (hazard ratio [HR], 0.825; 95% CI, 0.681 to 1.002; P=0.052)

Secondary Outcomes
- Reduction in exacerbations frequency and improvement in health status and spirometric values were observed with combination therapy compared to placebo (P<0.001)
- The incidence of pneumonia was higher among patients receiving fluticasone-containing treatments.

Criticisms

- The observed reduction in mortality did not reach predetermined statistical significance.
- High withdrawal rates, particularly in the placebo group, may have affected results.
- The trial may have been underpowered to detect a mortality benefit.

Funding

The trial was funded by GlaxoSmithKline.