Which patients with chronic obstructive pulmonary disease benefit from the addition of an inhaled corticosteroid to their bronchodilator? A cluster analysis

Rachael L Disantostefano, Hao Li, David B Rubin, David A Stempel, Rachael L Disantostefano, Hao Li, David B Rubin, David A Stempel

Abstract

Objective: To identify subsets of chronic obstructive pulmonary disease (COPD) patients who are more protected from exacerbations with the use of an inhaled corticosteroid/long-acting β2 agonist (ICS/LABA) combination, compared with the use of LABA monotherapy.

Design: Post hoc cluster analysis of patients from two randomised clinical trials of salmeterol/fluticasone propionate (SFC) and salmeterol (SAL) that had primary endpoints of moderate/severe exacerbation rates.

Setting: Centres in North America.

Participants: 1543 COPD patients were studied.

Interventions: SFC 50/250 µg or SAL 50 µg, twice daily.

Primary and secondary outcome measures: The analysis identified clusters of COPD patients more responsive to SFC versus SAL with respect to the annual rate of moderate/severe exacerbations and compared their baseline clinical characteristics.

Results: Overall, SFC significantly reduced the annual rate of moderate/severe exacerbations as compared with SAL alone (rate ratio (RR)=0.701, p<0.001). Three-patient clusters were identified: COPD patients receiving diuretics (RR=0.56, p<0.001); patients not receiving diuretics but with forced expiratory volume in 1 s (FEV1) reversibility ≥12% (RR=0.67, p<0.001) exhibited a substantial reduction in the annual rate of moderate/severe exacerbations relative to SAL. A third cluster, consisting of patients not receiving diuretics and without FEV1 reversibility, demonstrated no difference for SFC versus SAL. Patients receiving diuretics had a significantly higher prevalence of comorbid cardiovascular disease.

Conclusions: COPD patients receiving diuretics and those not receiving diuretics but with FEV1 reversibility >12% at baseline were significantly more likely to experience a reduction in COPD-associated exacerbations with SFC versus SAL alone.

Trial registration: NCT00115492, NCT00144911.

Figures

Figure 1
Figure 1
Interaction tree generated by supervised cluster analysis. MER, mean annual rate of moderate/severe exacerbations; SAL, salmeterol; SFC, salmeterol/fluticasone propionate combination.
Figure 2
Figure 2
Pooled analysis of SFC effect on the mean annual moderate/severe exacerbation rate by cluster. Ns, not significant (p>0.05); SAL, salmeterol; SFC, salmeterol/fluticasone propionate combination.

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