β-Blocker Therapy and Clinical Outcomes in Patients with Moderate Chronic Obstructive Pulmonary Disease and Heightened Cardiovascular Risk. An Observational Substudy of SUMMIT

Ann Am Thorac Soc. 2018 May;15(5):608-614. doi: 10.1513/AnnalsATS.201708-626OC.

Abstract

Rationale: Cardiovascular disease is a common comorbidity in patients with chronic obstructive pulmonary disease. Although β-blockers can be used safely in patients with chronic obstructive pulmonary disease, concerns remain regarding safety and efficacy interactions in patients using concomitant inhaled long-acting β-agonists.

Objectives: To compare the differential effects of long-acting β-agonist or inhaled corticosteroid use on clinical outcomes in patients with heightened cardiovascular risk treated and not treated with β-blockers.

Methods: We examined data from 16,485 participants in the SUMMIT study (Study to Understand Mortality and Morbidity in COPD) who were randomized to once-daily inhaled fluticasone furoate, vilanterol, fluticasone furoate/vilanterol combination, or placebo and examined the associations between treatment allocation and lung function, chronic obstructive pulmonary disease exacerbations, cardiovascular events, and all-cause mortality, stratified by baseline β-blocker therapy.

Results: Baseline β-blocker therapy was used by 31% (n = 5,159) of SUMMIT participants. There was no evidence of an interaction between baseline β-blocker therapy and the association between inhaled treatments and forced expiratory volume in 1 second at 3 months (P = 0.27), 6 months (P = 0.14), or 12 months (P = 0.33). The placebo-adjusted mean differences in post-bronchodilator forced expiratory volume in 1 second at 3 months in the vilanterol-alone group were 58 ml (95% confidence interval, 38-78) in those receiving baseline β-blocker therapy and 51 ml (95% confidence interval, 38-65) in those not receiving baseline β-blocker therapy. The placebo-adjusted mean differences in post-bronchodilator forced expiratory volume in 1 second at 3 months in the combination fluticasone furoate/vilanterol group were 85 ml (95% confidence interval, 65-105) in those receiving baseline β-blocker therapy and 68 ml (95% confidence interval, 54-82) in those not receiving baseline β-blocker therapy. Overall, there was no evidence of interaction by randomized treatment, including vilanterol alone or in combination with fluticasone furoate, for chronic obstructive pulmonary disease exacerbations (P = 0.18), cardiovascular composite events (P = 0.33), and all-cause mortality (P = 0.41).

Conclusions: There is no evidence to suggest that baseline β-blocker therapy reduces the respiratory benefits or increases the cardiovascular risk of inhaled long-acting β-agonists in patients with chronic obstructive pulmonary disease and heightened cardiovascular risk. Clinical trial registered with www.clinicaltrials.gov (NCT01313676).

Keywords: cardiovascular disease; chronic obstructive pulmonary disease; β-agonists; β-blockers.

Publication types

  • Comparative Study
  • Multicenter Study
  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Administration, Inhalation
  • Adrenergic beta-2 Receptor Agonists / administration & dosage*
  • Cardiovascular Diseases / epidemiology*
  • Cardiovascular Diseases / etiology
  • Cause of Death / trends
  • Disease Progression
  • Forced Expiratory Volume
  • Humans
  • Morbidity / trends
  • Prognosis
  • Pulmonary Disease, Chronic Obstructive / complications
  • Pulmonary Disease, Chronic Obstructive / drug therapy*
  • Pulmonary Disease, Chronic Obstructive / mortality
  • Risk Assessment / methods*
  • Risk Factors
  • Survival Rate / trends
  • United States / epidemiology

Substances

  • Adrenergic beta-2 Receptor Agonists

Associated data

  • ClinicalTrials.gov/NCT01313676