Effect of fluticasone propionate/salmeterol on arterial stiffness in patients with COPD

Respir Med. 2011 Sep;105(9):1322-30. doi: 10.1016/j.rmed.2011.05.016. Epub 2011 Jun 22.


Background: COPD is associated with increased arterial stiffness which may in part explain the cardiovascular morbidity observed in the disease. A causal relationship between arterial stiffness and cardiovascular events has not been established, though their strong association raises the possibility that therapies that reduce arterial stiffness may improve cardiovascular outcomes. Prior studies suggest that fluticasone propionate/salmeterol (FSC) may improve cardiovascular outcomes in COPD and we hypothesized that FSC would reduce arterial stiffness in these patients.

Methods: This multicenter, randomized, double-blind, placebo-controlled study compared the effects of FSC 250/50 μg twice-daily and placebo on aortic pulse wave velocity (aPWV) as determined by ECG-gated carotid and femoral artery waveforms. The primary endpoint was aPWV change from baseline at 12-weeks (last measure for each patient).

Results: 249 patients were randomized; the mean FEV(1) in each group was similar (55% predicted) and 60% of patients reported a cardiovascular disorder. At 12-weeks, aPWV between FSC and placebo was -0.42 m/s (95%CI -0.88, 0.03; p = 0.065). A statistically significant reduction in aPWV between FSC and placebo was observed in those who remained on study drug throughout the treatment period [-0.49 m/s (95%CI -0.98, -0.01; p = 0.045)]. A post hoc analysis suggested the effect of FSC was greater in patients with higher baseline aPWV.

Conclusion: FSC does not reduce aPWV in all patients with moderate to severe COPD, but may have effects in those with elevated arterial stiffness. Additional studies are required to determine if aPWV could serve as a surrogate for cardiovascular events in COPD.

Publication types

  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Albuterol / adverse effects
  • Albuterol / analogs & derivatives*
  • Albuterol / pharmacology
  • Androstadienes / adverse effects*
  • Androstadienes / pharmacology
  • Arteries / drug effects
  • Arteries / physiopathology*
  • Blood Flow Velocity / drug effects
  • Cardiovascular Diseases / chemically induced
  • Cardiovascular Diseases / physiopathology*
  • Double-Blind Method
  • Drug Combinations
  • Female
  • Fluticasone-Salmeterol Drug Combination
  • Forced Expiratory Volume / drug effects*
  • Humans
  • Male
  • Middle Aged
  • Pulmonary Disease, Chronic Obstructive / complications
  • Pulmonary Disease, Chronic Obstructive / drug therapy
  • Pulmonary Disease, Chronic Obstructive / physiopathology*
  • Sympathomimetics / adverse effects*
  • Sympathomimetics / pharmacology
  • Treatment Outcome
  • Vascular Resistance / drug effects*


  • Androstadienes
  • Drug Combinations
  • Fluticasone-Salmeterol Drug Combination
  • Sympathomimetics
  • Albuterol